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  • 1
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Journal of neurochemistry 73 (1999), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : We investigated oxidative damage to the c-fos gene and to its transcription in the brain of Long-Evans rats using a transient focal cerebral ischemia and reperfusion (FCIR) model. We observed a significant (p 〈 0.001) increase in the immunoreactivity to 8-hydroxy-2′-guanine (oh8G) and its deoxy form (oh8dG) in the ischemic cortex at 0-30 min of reperfusion in all 27 animals treated with 15-90 min of ischemia. Treatment with a neuronal nitric oxide synthase (nNOS) inhibitor, 3-bromo-7-nitroindazole (60 mg/kg, i.p.), abolished the majority but not all of the oh8G/oh8dG immunoreactivity. Treatment with RNase A reduced the oh8G immunoreactivity, suggesting that RNA may be targeted. This observation was further supported by decreased levels of mRNA transcripts of the c-fos and actin genes in the ischemic core within 30 min of reperfusion using in situ hybridization. The reduction in mRNA transcription occurred at a time when nuclear gene damage, detected as sensitive sites to Escherichia coli Fpg protein in the transcribed strand of the c-fos gene, was increased 13-fold (p 〈 0.01). Our results suggest that inhibiting nNOS partially attenuates FCIR-induced oxidative damage and that nNOS or other mechanisms induce nuclear gene damage that interferes with gene transcription in the brain.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract English sole (Parophyrs vetulus) in Puget Sound, Washington, USA are at risk of hepatocarcinogenesis specifically in areas adjacent to polluting industrial effluents. A question concerning population and ecosystem survival is whether any of the effects of etiopathologic change are reversible. This has been approached by looking for evidence of tumor accelerating effects in an exposed population. Cellular parameters were determined by flow cytometry for hepatocytes of English sole. Cells containing hyperdiploid DNA not present in fish from reference waters, Port Madison, were found in all non-tumor-bearing and tumor bearing fish taken from a polluted site, Eagle Harbor, where incidence of hepatic neoplasia approaches 30%. Induction of altered DNA content in the exposed general hepatocyte population suggests environmental induction rather than an association with lesionsper se. In contrast, glutathione levels in hepatocytes (0.8–3.2 nmol/mg protein), were little influenced by the exposure site, consistent with the apparent lack of protection against chemically induced carcinogenesis in English sole. Association of altered DNA content with exposure site is significant for its potential contribution to biological acceleration and evidence of tumor promotion found at the tissue and organismic levels. The results support the notion that hepatocarcinogenesis in English sole in Eagle Harbor has a multi-year exposure etiology, in which potentially reversible accelerating influences have a role, and that glutathione conjugation is an inadequate mode of detoxification for these fish.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0730-2312
    Keywords: β1→3N-acetylglucosaminyltransferase ; cancer-associated carbohydrate antigens ; biosynthesis ; glycosphingolipid ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Human colonic adenocarcinoma DLD-1 cells were grown under conditions which induce characteristics of differentiated cells using medium containing 0.8% N,N-dimethylformamide in order to study alterations in glycosphingolipid glycosyltransferase activities during this process. Analysis of biosynthetic reactions involved in lacto-series antigen synthesis revealed no changes in the specific activities of either β1→4galactosyltransferase or α1→3/4fucosyltransferase with N,N-dimethylformamide treatment. However, a dramatic decrease of from 14- to 20-fold in the β1→3N-acetylglucosaminyltransferase activity was observed in the treated cells. This enzyme catalyzes the rate-limiting step in lacto-series core chain synthesis. This is consistent with the pattern of regulation of lacto-series antigen expression found to occur during oncogenesis in human colonic mucosa (Holmes EH, Hakomori S, Ostrander GK: J Biol Chem 262:15649, 1987). Total glycolipids from untreated and N,N-dimethylformamide-treated cells were isolated and subjected to TLC immunostain analysis and solid phase radioimmunoassay with a series of monoclonal antibodies specific for lacto-series-based carbohydrate antigens. A decrease of about 2-fold or less in the quantity of lacto-series antigens was observed as a consequence of N,N-dimethylformamide treatment in both neutral glycolipid and ganglioside fractions. The results suggest that only very low levels of β1→3N-acetylglucosaminyltransferase activity are required for the steady state expression of significant levels of lacto-series based glycolipids and that modulation of its activity levels by N,N-dimethylformamide treatment in DLD-1 cells represents a convenient in vitro system for studying aspects of regulation of lacto-series antigen expression.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0730-2312
    Keywords: β1 → 3galactosyltransferase ; stable expression ; glycolipids ; lacto-series type 1 chain ; Lewis antigens ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Transient expression of a human colonic adenocarcinoma Colo 205 cell derived cDNA in cell lines which ordinarily express only neolacto-series glycolipids has resulted in the expression of a β1 → 3galactosyltransferase gene responsible for synthesis of glycolipids based upon the lacto-series type 1 core chain. Calcium phosphate transfected cells were panned on anti-lgM coated plates after initial treatment with a combination of monoclonal antibodies specific for type 1 chain terminal structures (TE-3) and a very broadly specific antibody reactive with multiple type 1 chain derivatives (TE-2). Adherent cells after panning were capable of efficiently transferring Gal in β1 → 3-linkage to the acceptor glycolipid Lc3. Using these reagents, clones of stably transfected human colonic adenocarcinoma HCT-15 cells were produced and isolated. Parental HCT-15 cells do not express type 1 chain based antigens. The nature of the type 1 chain based antigens produced in each of these clones was analyzed by solid phase antibody binding assays. Three types of behavior were observed. Formation of type 1 terminal structures that were either exclusively sialylated or fucosylated, or a mixture of sialylated and fucosylated determinants occurred. In contrast, no difference in type 2 antigen expression between any clone and the parental cells was observed. These data suggest that coordination of subsequent reactions capable of modifying type 1 chain structures is not the same in all clones. The relationship of these results to aspects of cellular regulation of carbohydrate biosynthesis is discussed. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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