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  • 1
    ISSN: 1432-0584
    Keywords: Anthracyclines ; Verapamil ; Bone marrow progenitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Drug-induced myelotoxicity is usually the dose-limiting factor of treatment of malignant tumors with cytostatic drugs. Suppression of in vitro myelopoiesis (CFU-GM) by cytostatics may be a suitable model reflecting the in vivo situation. Thus the inhibitory effects of the anthracyclines doxorubicin, theprubicin, idarubicin and cytorhodin S on CFU-GM were compared. Normal human bone marrow cells were incubated with these drugs for one hour and alternatively, for the whole culture period. For each substance and each incubation time a dose-response curve was established and the D50 determined. As certain calcium antagonists can increase the toxicity of some cytostatic drugs in various tumor models, the effect of the addition of verapamil (2µM) was also investigated. It could be shown, that the myelotoxicity on CFU-GM of the drugs mentioned above was not increased after short-term or permanent exposure to this calcium antagonist.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 64 (1992), S. A132 
    ISSN: 1432-0584
    Keywords: Hepatitis A virus ; In vitro myelopoiesis ; Long-term bone marrow cultures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Perturbations of hematopoietic regulation ranging from transient granulocytopenia to rare cases of bone marrow failure are associated with infections due to hepatitis A virus (HAV). In an attempt to elucidate the pathogenetic mechanisms we had previously established that HAV has a direct suppressive effect on human bone marrow progenitors (CFU-GM, -GEMM, BFU-E). These studies were extended to long-term bone marrow cultures (LTBMC): Inoculation of bone marrow mononuclear cells with HAV did not interfere with the establishment of an adherent stromal layer, nor did the inoculation of already established layers cause any morphologically recognizable changes to the stroma. In contrast, a significant and progressive decline of the CFU-GM content in the culture supernatants was demonstrated. HAV antigen was detected by APAAP stain in a subpopulation of stromal cells, and sequential estimations of virus titers in the supernatants provided evidence for viral replication in primary bone marrow cultures. Interferon-gamma and tumor necrosis factor-alpha levels of infected cultures did not differ from those of uninfected controls. These findings argue for a direct suppression of (pre-) CFU-GM by HAV in a model system (LTBMC) lacking an immune defense which would limit viral replication.
    Type of Medium: Electronic Resource
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