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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 309-314 
    ISSN: 1432-1912
    Keywords: Antitumor therapy ; Cl− secretion ; Colon (rat) ; CPT-11 ; Diarrhoea ; Irinotecan Thromboxane A2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Irinotecan (CPT-11) is active against a broad range of human cancer. One of the side-effects of irinotecan is a strong diarrhoea. In order to investigate the mechanism underlying this diarrhoea, the effect of irinotecan on anion secretion across the isolated rat distal colon was studied. Irinotecan caused a concentration-dependent increase in short-circuit current (Isc). The increase in Isc was completely dependent on the presence of Cl− ions and was supressed by furosemide and the Cl− channel blocker NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), indicating that it is caused by a Cl− secretion. The secretory response was inhibited by indomethacin, 1-benzylimidazole, a thromboxane synthase inhibitor, and SK&F 88046 ((N,N′bis-[7-(3-Chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoquinolyl)disulfonylimide), a thromboxane A2 receptor blocker. In isolated crypts irinotecan had no effect on the membrane potential. Consequently, the secretion induced by irinotecan is an indirect one, caused by the stimulation of eicosanoid production, e.g. thromboxane A2, in the subepithelial tissue.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 309-314 
    ISSN: 1432-1912
    Keywords: Key words Antitumor therapy ; Cl- secretion ; Colon (rat) ; CPT-11 ; Diarrhoea ; Irinotecan ; Thromboxane A2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Irinotecan (CPT-11) is active against a broad range of human cancer. One of the side-effects of irinotecan is a strong diarrhoea. In order to investigate the mechanism underlying this diarrhoea, the effect of irinotecan on anion secretion across the isolated rat distal colon was studied. Irinotecan caused a concentration-dependent increase in short-circuit current (Isc). The increase in Isc was completely dependent on the presence of Cl- ions and was supressed by furosemide and the Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), indicating that it is caused by a Cl- secretion. The secretory response was inhibited by indomethacin, 1-benzylimidazole, a thromb- oxane synthase inhibitor, and SK&F 88046 ((N,N′-bis[7-(3-Chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoquinolyl)disulfonylimide), a thromboxane A2 receptor blocker. In isolated crypts irinotecan had no effect on the membrane potential. Consequently, the secretion induced by irinotecan is an indirect one, caused by the stimulation of eicosanoid production, e.g. thromboxane A2, in the subepithelial tissue.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-069X
    Keywords: Key words Mast cells ; c-kit ; Glucocorticoids ; IL-3 ; receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the effects of glucocorticoids on IL-3-dependent proliferation and c-kit expression of cells of the mouse mast cell line, MC/9. Glucocorticoids (dexamethasone, prednisolone, and hydrocortisone) inhibited IL-3-dependent MC/9 cell proliferation, whereas sex steroids (progesterone, β-estradiol, and testosterone) had no effect. Flow cytometric analysis revealed that glucocorticoids reduced the expression of the IL-3 receptor on MC/9 cells. Immunoblot and Northern blot analyses indicated that glucocorticoids also reduced the expression of both c-kit protein and c-kit mRNA transcript. Furthermore, the adhesion of MC/9 cells to stem cell factor-expressing NIH/3T3 cells was reduced following glucocorticoid treatment. Our results indicate that glucocorticoids inhibit IL-3-dependent MC/9 mast cell proliferation, with an accompanying decrease in IL-3 receptor expression. Glucocorticoids also reduced c-kit expression on MC/9 cells resulting in a decreased adhesion to NIH/3T3 fibroblasts.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Clonality ; CML ; T lymphocyte ; PGK ; bcr gene rearrangement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify the extent of cell lineage involvement in chronic myelogenous leukemia (CML), we investigated the bcr gene rearrangement and clonality using the X-chromosome-linked restriction fragment length polymorphism (RFLP) methylation method in T lymphocytes and granulocytes. We examined the granulocyte and T-cell fractions from the peripheral blood of seven female patients with CML during the chronic phase; patients were heterozygous for RFLPs at the phosphoglycerate kinase (PGK) or the hypoxanthine phosphoribosyltransferase (HPRT) gene. RFLP-methylation analysis of granulocytes demonstrated a monoclonal pattern in six of the seven patients and a rearrangedbcr gene in all seven patients. In contrast, T lymphocytes exhibited a polyclonal pattern in six cases; in one case, a faint band was observed following methyl-sensitive enzyme cleavage. Thebcr gene analysis in T lymphocytes showed the germline in every case. Our results indicate that the majority of T lymphocytes are polyclonal during the chronic phase of CML and confirm previous reports based on glucose-6-phosphate dehydrogenase, cytogenetic, andbcr rearrangement analyses.
    Type of Medium: Electronic Resource
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