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  • 1
    Electronic Resource
    Electronic Resource
    Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases (1997)
    Springer
    Virchows Archiv 431 (1997), S. 189-194 
    Details
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; Liver disease ; Hepatitis ; Hepatocytes ; Kupffer cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis(AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050087
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  • 2
    Electronic Resource
    Electronic Resource
    Carbostyril-based beta-adrenergic agonists: evidence for long lasting or apparent irreversible receptor binding and activation of adenylate cyclase activity in vitro (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 129-137 
    Details
    ISSN: 1432-1912
    Keywords: Rat reticulocytes ; Beta-adrenoreceptors ; Apparent irreversible ligand ; Carbostyril derivatives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The interaction of the carbostyril derivatives 5-[2-[[1-(4-aminophenyl)-2-methyl-prop-2-yl]amino]-1-hydroxyethyl]-8-hydroxycarbostyril (carbo-amine) and 5-[2[[3-[4-(bromoacetamido)phenyl]-2-methylprop-2-yl]amino]1-hydroxyethyl]-8-hydroxycarbostryril (carbo-Br) with the rat reticulocyte beta-adrenoreceptor system has been partially characterized. In the absence of a guanine nucleotide, the concentration of carbo-amine, carbo-Br and (−)isoprenaline that inhibited (−)-[125I]iodocyanopindolol ([125I]CYP) binding by 50% (IC50) was 5.9 ± 0.2, 3.3 ± 0.3 and 49 ± 3 nM, respectively. In the presence of a guanine nucleotide, the (IC50) values were carbo-amine, 21 ± 0.6 nM; carbo-Br, 7.6 ± 0.3 nM and (−)isoprenaline, 813 ± 66 nM. Preincubation of membranes with either of the carbostyril congeners followed by washing reduced specific [125I]CYP binding capacity without changing the K D value for the remaining receptors. The beta-antagonist nadolol largely prevented the receptor reduction induced by the carbostyril compounds. Incubation of membranes for 18 It at 25°C resulted in an 11 % recovery of the carbo-amine-induced receptor loss and no recovery of the receptors lost by preincubation with carbo-Br. However, the carbo-amine induced receptor loss could be largely reversed (80%) by membrane heating at 45°C whereas little reversal (〈 10%) was observed with the carbo-Br pretreated membranes. The concentration of carbo-amine, carbo-Br and (−)isoprenaline that stimulated halt-maximal cAMP formation in reticulocyte membranes was 17.8 ± 3.1, 8.2 ± 2.1 and 241 ± 17 nM, respectively, and all 3 agonists produced the same maximal response. Initial cAMP formation stimulated by the carbostyril derivatives and (−)isoprenaline was blocked by concurrent addition of propranolol. However, the addition of propranolol after 7 min of incubation with either of the two carbostyril derivatives did not affect further cAMP production whereas with (−)isoprenaline further cAMP production was blocked. The data indicate that both carbostyril-derivatives are potent, full beta-adrenoreceptor agonists and the carbo-amine bound to the beta-adrenoreceptor in a tight, slowly dissociating manner whereas carbo-Br binding shows an apparent irreversible interaction with the receptor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00165134
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    Paper (German National Licenses)
    Fulltext
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