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  • 1
    ISSN: 1432-1041
    Keywords: Agranulocytosis ; OPC-8212 ; quinolinone derivative ; 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone ; bone-marrow progenitor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (OPC-8212) is a quinolinone derivative with positive inotropic properties. In order to elucidate the effect of OPC-8212 on the haemopoietic system we studied its in vitro effect on bone-marrow progenitor cells (granulocyte/monocyte colonyforming units [CFU-GM] and erythroid burst-forming units [BFU-E]), on the proliferation and secretion of granulocyte/monocyte colony-stimulating factor (GM-CSF) and interferon-γ (IFN-γ) by peripheral lymphocytes, and on GM-CSF secretion by fibroblasts from healthy individuals. The dose-effect relations of OPC-8212 on CFU-GM proliferation and on lymphocytic GM-CSF secretion showed no effect at very low drug concentrations, with a threshold at the lower end of the therapeutic range and highly significant dose-dependent inhibition at concentrations above that threshold. BFU-E, peripheral lymphocyte proliferation and lymphocytic IFN-γ secretion were depressed, although to a lesser extent, in a linear dose-dependent fashion. OPC-8212 did not affect GM-CSF secretion by one strain of fibroblasts but reduced it at higher concentrations in assays with another strain of cells. We conclude that direct toxic effects on bone-marrow progenitor cells, in combination with the inhibition of cytokines involved in the regulation of haemopoiesis in certain susceptible individuals, may be responsible for idiosyncratic reactions to OPC-8212.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 14 (1985), S. 279-281 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A group of 46 patients with melphalan-resistant multiple myeloma was treated according to the M-2 protocol with melphalan, prednisolone, BCNU, cyclophosphamide, and vincristine. According to the Salmon and Durie classification, four patients had stage II A; 36, stage III A; and six, stage III B disease. Treatment resulted in five patients (11%) entering remission, while 21 (46%) had stable and 20 (43%) had progressive disease. The median survival for all patients was 12.5 months, patients in remission surviving longer (median 46 months) than those with stable disease (median 15.4 months) or progressive disease (median 6.9 months). Compared with other treatment regimens used in melphalan-resistant myeloma, the remission rate is low but the median survival exceeds that reported by most other authors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 52 (1986), S. 305-315 
    ISSN: 1432-0584
    Keywords: T Cell Clones ; Myelopoiesis ; CFU-GM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Regulatory effects of mixed lymphocyte culture (MLC)-derived CD4+ human T cell clones on granulocyte-macrophage colony (CFU-GM) formation by normal bone marrow (BM) were studied in an initial attempt to establish an in vitro model for the negative feedback control of myelopoiesis by alloactivated T cells. This is likely to be of clinical significance in the aberrant control of haematopoiesis during some cases of graft-versus-host disease (GVHD) after allogeneic BM transplantation. Whilst 5 such alloproliferative clones generally failed to suppress CFU-GM, the majority of clones with natural killer (NK)-like activity [10], or those with suppressive activity in MLC [2], regularly and strongly suppressed in this system, reinforcing the view that certain T cells may have potent negative regulatory effects on haematopoiesis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Non-Hodgkin's lymphomas ; Chemotherapy ; Consolidation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty four patients with high grade malignant NHL (stage II 8, stage III 4, stage IV 12 patients respectively) were treated with a response-oriented regimen: Treatment was initiated according to the CHOP-protocol. Patients achieving at least a partial remission after 2 and a complete remission (CR) after 4 cycles were continued on CHOP to a total of 9 cycles. Patients not meeting these criteria were switched to a combination of Etoposide, Ifosfamide, Methotrexate, and Bleomycin (VIM-Bleo). With CHOP treatment, 16 patients (67%) achieved a CR. Of the remaining 8, 7 were treated with VIM-Bleo; 5 of these entered CR for a overall CR rate of 21/24 (88%). With a median follow up of 28 months 7 patients relapsed: 6 relapses occurred in patients with a rapid initial response and treated only with CHOP. We conclude, that there is a significant risk of relapse even in patients readily responding to CHOP and that consolidation therapy with a non cross-resistant regimen may improve results in these patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0584
    Keywords: HLA-class II ; Hematopoietic progenitor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A panel of alloindifferent monoclonal antibodies (MAB's) was used in complement-dependent lysis to characterize human myeloid, erythroid and multipotential progenitors (CFU-GM, BFU-E, CFU-GEMM) for their expression of MHC class II HLA-DR, -DP, and -DQ products. 7–16 donors were tested in each system. MAB Tü 34, detecting DR products, caused reduction of CFU-GM by a mean of 89%, whereas BFU-E and CFU-GEMM were reduced by 67% and 66% respectively. 35% of CFU-GM, 27% of BFU-E and 32% of CFU-GEMM were lysed by MAB B7/21, recognizing HLA-DP determinants, while Tü 22, binding HLA-DQ antigens, lysed 32% only of CFU-GM and did not lyse the other progenitors. Employing the “broad” MAB Tü 39, which binds at least DR and DP, inhibition of colony formation by CFU-GM was generally greater than that caused by Tü 34 alone or even by combinations of Tü 34, Tü 22, and B7/21. This suggests that there may be a subset of DR−, DP−, DQ− hematopoietic progenitors, which nonetheless bind MAB Tü 39, previously proposed as a candidate for the recognition of novel class II antigens.
    Type of Medium: Electronic Resource
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  • 6
    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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  • 7
    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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