[Thrombopoietic activity of human embryonic organs].
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Biomedical subjects
Publications and source records attributed to F Krizsa.
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The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.
The shedding process of the mouse erythrocyte binding receptors of human peripheral lymphocytes of a healthy donor group was compared to that of patients with chronic lymphocytic leukemia. The shedding process exhibited significant differences with respect to the groups tested, suggesting that the mouse erythrocyte binding receptors were altered during leukemic transformation or that the leukemic cells were fixed in a stage of maturation.
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Injection of medium conditioned by a murine myelomonocytic leukaemic cell-line (WEHI-CM) stimulates platelet production in irradiated, bone marrow reconstituted mice. Media conditioned by the growth of normal bone marrow cells (BM-CM) or by a lymphoid leukaemia cell line had no effect on platelet production. However, the effect of WEHI-CM on platelet production was further enhanced when injected along with BM-CM, indicating that more than one factor may play a role in the regulation of megakaryocytopoiesis.
Light and dark field autoradiography of semithin sections prepared 6 h after a treatment with APS showed that the incorporation of H3-leucine into the cells of the convoluted tubules of the kidney was increased in mice. There was no difference in the H3-leucine incorporation in the liver, either in thrombocytopenic or in untreated animals. The increased incorporation of leucine in the kidney in APS-induced thrombocytopenia showed coincidence with increased thrombopoietin production.
Studies have been carried out on B and T cells in bone marrow and peripheral blood from patients with paraproteinaemia. The peripheral blood of patients with multiple myeloma showed a significant increase of B cells, mainly lymphoid cells bearing immunoglobulins corresponding to the paraproteins, while in patients with benign monoclonal gammopathy only a slight increase of B cells and a moderate decrease of T cells have been found. As to the bone marrow, the B cell population was significantly raised in patients with multiple myeloma, but it remained unchanged in patients with benign monoclonal gammopathy. Our findings may offer a new possibility to distinguish between these two diseases and provide further data to their pathogenesis.
The development of a suitable bone marrow derived adherent cell population appears to be essential for the prolonged maintenance of haemopoietic stem cells in vitro. When established adherent layers are inoculated with freshly isolated bone marrow cells, proliferation of stem cells (CFU-S) regularly occurs both in the adherent layer and amongst the non-adherent cells. Furthermore, CFU-S present within the adherent layer are able to regenerate both themselves and the "non-adherent" CFU-S. One day after re-feeding the cultures (by removal of half the growth medium and addition of fresh medium) both the "non-adherent" and the "adherent" CFU-S are in a high cycling state (greater than 40% kill with 3HTdR). This proportion decreases with time of re-feeding and 5-7 days later the majority of "adherent" and "non-adherent" CFU-S are in a low cycling state ( less than 10% 3HTdR kill). Following a further re-feeding, CFU-S again enter a high cycling state.
F-leurosine (formyl-leurosine) was found to exert a thrombocytopoietic effect in CFLP mice. The effect was most pronounced in a dose of 1.0 mg/kg. The increased activity of the megakaryocyte system was not due to thrombocytopenia. The preparation induced in the bone marrow an increasing megakaryocyte formation (increase of the megakaryocyte index, a shift to the left in the qualitative composition of the giant cells, increase of the 75Se-methionine incorporation). F-leurosine seems to exert its effect through a direct stimulation of the megakaryocyte system, which might be utilized in therapy.
Injections of 1 to 2.5 X 10(8) syngeneic, uninjured platelets did not diminish the circulating platelet count nor the bone marrow megakaryocyte content in mice, and did not influence the incorporation of 75selenomethionine into circulating platelets. However, platelet homogenates, prepared by repeated freezing and thawing of identical amounts of syngeneic paltelets induced a dose-dependent thrombocytopenia along with a diminution on bone marrow megakaryocyte content, and a decrease in 75 selenomethionine incorporation. Other circulating blood cell counts were not diminished after platelet homogenates, and three intravenous doses of homogenates prepared from 0.7 to 1 X 10(5) syngeneic buffy coat cells failed to influence circulating platelet count or 75 selenomethionine incorporation.
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After administration of a single 1 IU dose of exogenous erythropoietin to mice or by stimulating endogenous erythropoietin production with androgen, the animals' thrombocytopoiesis, measured with selenomethionine incorporation, decreased. The suppression of endogenous erythropoietin level by hypertransfusion also caused a decrease of thrombocytopoiesis.
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