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Biomedical subjects

S Ebbe

Publications and source records attributed to S Ebbe.

At least 37 records · Page 2Linked to original sources
PubMed1985

Modulation of radiation-induced hemopoietic suppression by acute thrombocytopenia.

Modifications of radiation-induced hemopoietic suppression by acute thrombocytopenia were evaluated. Immediately before or after exposure to sublethal irradiation, mice were given a single injection of anti-mouse platelet serum (APS), normal heterologous serum, neuraminidase (N'ase), or saline, or no further treatment was provided. Hemopoiesis was evaluated by blood cell counts, hematocrits, and incorporation of [75Se]selenomethionine into platelets. APS and N'ase induced an acute thrombocytopenia from which there was partial recovery before the platelet count started to fall from the radiation. During the second post-treatment week, both thrombocytopoiesis and erythropoiesis were greater in mice that received APS or N'ase in addition to radiation than in control irradiated mice. Differences in leukopoiesis were not apparent. Therefore, both thrombocytopoiesis and erythropoiesis appeared to be responsive to a stimulus generated by acute thrombocytopenia in sublethally irradiated mice.

Animals↗
PubMed1985

Correlation between bioassay and radioimmunoassay for erythropoietin in human serum and urine concentrates.

Both immunoreactive erythropoietin (Ep) and biologically active Ep were measured in 23 samples of human serum and 21 concentrates of human urine. Immunoreactive Ep was measured by radioimmunoassay (RIA). Biological activity was determined in the plethoric mouse bioassay in which 59Fe incorporation was converted to units of Ep from standard reference curves. Low values for Ep were determined from standard curves plotted as probits to improve sensitivity for levels of Ep as low as 30 mU/ml. Ep levels in 35 samples ranged between 30 and 1000 mU/ml by both assays; in 9 samples Ep was 15.2-37.5 mU/ml by RIA but was not detectable by bioassay. Analysis of the data for the 35 samples in which Ep could be measured by both assays showed a strong correlation between the values obtained by the two assays. These results indicate that the RIA used in these experiments detects biologically active Ep in human serum and urine when it is present in amounts only moderately higher than normal. The ultrafiltration method used for preparation of urine samples was effective in concentrating Ep in some urines, but the results were too erratic and nonquantitative to permit its use as a method for quantifying human urinary Ep excretion.

Biological Assay↗
PubMed1985

Independence of megakaryocyte number and size in long-term cultures of normal mouse marrow.

Megakaryocytopoiesis was evaluated in long-term cultures of normal murine marrow to determine whether the number and size of megakaryocytes were independent or interdependent. Numbers of megakaryocytes and granulocytes varied widely in different experiments, due, in part, to varying concentrations of hydrocortisone in the culture medium. The sizes of acetylcholinesterase-positive cells were the same in cultures with as much as a 20-fold difference in megakaryocyte numbers. These results indicate that, in the closed culture system containing normal stromal cells, megakaryocyte size and number are not reciprocal as they were in many previously reported cultures of S1/S1d mouse marrow. The results suggest that separate stromal functions may determine precursor cell proliferation and nuclear endomitosis in megakaryocytes in vitro. The relationship of these findings to regulation of megakaryocytopoiesis in vivo remains speculative.

Acetylcholinesterase↗
PubMed1984

Mean platelet volume: the need for a reference method.

The time course of artifactual effects due to anticoagulants, specimen temperature, and interval between venipuncture and analysis on platelet volume measurements was evaluated. Split specimens were analyzed using hydrodynamic focusing, and platelet distributions were computed using a least-squares fit to a log-normal distribution. Significant artifacts resulted from exposure to EDTA, cooling to room temperature, and delay in exposure to anticoagulant. The artifactual effect of EDTA is extreme and time dependent. Collection of blood in Buffered Citrate, Acid Citrate Dextrose, or Pyridoxal-5'-phosphate supplemented Citrate yielded stable and equivalent results with rapid anticoagulation and incubation at 37 degrees C for up to six hours.

Anticoagulants↗
PubMed1984

Macrocytic megakaryocytes in cultures of S1/S1d bone marrow.

The thrombocytopoietic system of S1/S1d mice is characterized by macromegakaryocytosis and megakaryocytopenia, but the mechanisms responsible for reciprocal abnormalities of megakaryocyte number and size are unknown. These mice have a genetically determined abnormality of their hemopoietic microenvironment that can, in part, be reproduced as abnormal adherent stromal cells in bone marrow cultures. Cultures of bone marrow were therefore done to determine if the megakaryocytic abnormalities of S1/S1d marrow would also be reproduced in them. Cultures composed entirely of S1/S1d cells showed persistent macrocytosis of megakaryocytes when compared with cultures of normal +/+ marrow. At various times of culture, there were also reduced numbers of megakaryocytes, total cells, and granulocytes in the supernatants of S1/S1d cultures. Mixed cultures of S1/S1d and +/+ cells yielded inconclusive findings. The fact that macromegakaryocytosis occurred in cultures of S1/S1d marrow strongly suggests that its in vivo determinants were, in part, reproduced in culture.

Acetylcholinesterase↗
PubMed1982

Immature megakaryocytes in the mouse: physical characteristics, cell cycle status, and in vitro responsiveness to thrombopoietic stimulatory factor.

The heterogeneity among immature megakaryocytes has been examined by physical properties, cell cycle status, and responsiveness to thrombopoietic stimulatory factor. Three types of immature megakaryocytes exist that can be recognized by acetylcholinesterase staining, nuclear shape, high nucleus/cytoplasm ratio, and small size (8--18 mu) with respect to mature megakaryocytes (greater than 18 mu). These three acetylcholinesterase-containing cell types are distinguished by their nuclear configuration: a round, indented, and lobed nucleus. The lobed cell type was found to overlap with and enhance detection of megakaryoblasts (stage I megakaryocytes). These cells had a sedimentation velocity range of 3.5--19.0 mm hr-1 and a density range of 1.072--1.095 g cm-3. Separation of these three classes of immature megakaryocytes was achieved by equilibrium density centrifugation with modal buoyant densities of 1.079 g cm-3 (round), 1.084 g cm-3 (indented), and 1.089 g cm-3 (lobed). In the presence of thrombopoietic stimulatory factor, the round nucleated cells, but not the indented or lobed nuclei morphology, were observed to develop into large mature megakaryocytes in 60-hr semisolid cell cultures. Development of two cell groups, or colonies of megakaryocytes, was not observed during this in vitro incubation period. In vivo treatment with hydroxyurea indicated that 57.5% +/- 19% of the round nucleus form were actively synthesizing DNA. No reduction in the numbers of indented or lobed nucleus forms were observed following hydroxyurea treatment. The data in this report strongly support the concept that these three types of immature megakaryocytes reflect the early maturation stages occurring in megakaryocyte differentiation.

Acetylcholinesterase↗
PubMed1981

Megakaryocytopoiesis in irradiated, splenectomized mice.

The hypomegakaryocytic state that develops after exposure to sublethal doses of ionizing radiation was evaluated in splenectomized and intact mice. The percentage reduction of marrow megakaryocytes was greater than that of platelets at comparable times post-irradiation. After initial recovery a secondary drop in platelet counts occurred earlier in intact than in splenectomized mice. The average size of mature megakaryocytes was found to be increased, due primarily to marked reductions in megakaryocytes of smaller size. These results indicate that the spleen acts more to reduce than to increase the platelet count after exposure to sublethal doses of whole body radiation and that megakaryocyte size may be increased by reduction in numbers of small megakaryocytes without an increase in large megakaryocytes.

Animals↗
PubMed1979

Does autoregulation of megakaryocytopoiesis occur?

Although a major regulator of thrombocytopoiesis is the number of circulating platelets, several observations suggest that independent alternative regulatory mechanisms may exist. In some situations there is a curious association of megakaryocytopenia and megakarocytic macrocytosis in spite of normal platelet counts. If macrocytosis is considered as a sign of stimulation, this association suggests a cause and effect relationship between decreased numbers and increased size of megakaryocytes. This thesis was tested by examining the delayed effects of sublethal irradiation and the acute effects of hydroxyurea in mice. It was found that megakaryocytopenia and macromegakaryocytosis occurred together and that platelets counts were either normal or only slightly reduced. Therefore it was concluded that normal numbers of platelets could be produced by decreased numbers of megakaryocytes. Megakaryocytopenia appeared to be compensated, in part, by increased size of megakaryocytes, but the mechanism by which this occurred has not been elucidated. It is postulated that a reduction in the number of cells of the megakaryocytic system is sensed by a homeostatic mechanism that then acts to stimulate the cells that are present. This stimulation may then be manifested as macrocytosis of megakaryocytes.

Animals↗
PubMed1978

Regulation of megakaryocytes in W/Wv mice.

W/Wv mice were injected with antiplatelet serum to produce thrombocytopenia or with platelet transfusions to induce thrombocytosis. The responses of their platelets and megakaryocytes were followed to determine if proliferative abnormalities of the megakaryocytic system would be detected. W/Wv mice responded normally to the stimulation from thrombocytopenia with rebound thrombocytosis, macromegakaryocytosis, and macrothrombocytosis. The megakaryocytes of these mice became smaller than normal in response to post-thrombocytopenic rebound thrombocytosis but not to transfusion-induced thrombocytosis. Thus, endogenous thrombocytosis appeared to be a more potent suppressor of megakaryocyte growth than exogenous. These results failed to reveal an effective abnormality of the thrombocytopoietic regulatory system of W/Wv mice in spite of their intrinsically reduced numbers of megakaryocytes and the well known defect of stem cell proliferation. Thrombocytopoietic regulation appeared, therefore, to occur mainly at the committed, rather then pluripotential, stem cell level, and normal responses of the platelet system were observed in spite of severe abnormalities at the pluripotential stem cell level.

Anemia, Hemolytic↗
PubMed1978

Megakaryocytic responses to thrombocytopenia and thrombocytosis in Sl/Sld mice.

Sl/Sld mice maintain normal platelet counts in spite of a reduced number of megakaryocytes, but their megakaryocytes are macrocytic. The present studied were done to analyze platelet turnover in the steady state and thrombocytopoietic responses to perturbations of the platelet count. Platelet production, estimated with 35S incorporation in the steady state, blood volume, and total complement of peripheral platelets were normal. Sl/Sld mice responded to thrombocytopenia with normal degrees of macromegakaryocytosis and production of macrocytic platelets, but rebound thrombocytosis did not occur. Their megakaryocytes were unusually responsive to transfusion-induced thrombocytosis, showing a prompt and substantial reduction in size. Platelet turnover was normal in undisturbed Sl/Sld mice, and feedback regulation occurred. However, increased numbers of platelets were not produced in response to stimulation. The findings are consistent with the possibility that their megakaryocytes are large because of stimulation rather than a direct local effect of the abnormal microenvironment.

Animals↗
PubMed1977

Thrombocytotic suppression of megakaryocyte production from stem cells.

Megakaryocytopoiesis in the spleens of lethally irradiated mice transplanted with marrow cells was suppressed by platelet transfusions. In one group of experiments, animals were irradiated and transfused with bone marrow cells on day O. They were then given either no treatment, platelets, platelet-poor plasma, or saline on days 0, 2, 4, 6, and 8, and then were sacrificed on day 10. Megakaryocytes per section in the spleens of mice receiving platelets were 24%-48% of the values in the groups given plasma, saline, or bone marrow only. The number of pure megakaryocyte colonies was also diminished by platelet hypertransfusion. Another experiment examined the effect of platelets or plasma administered on days 1 and 2 or days 6 and 7 after irradiation and bone marrow transfusion. Hypertransfusion on days 6 and 7 was as effective in suppressing megakaryocytopoiesis as hypertransfusion every other day for 10 days. Animals given platelets or plasma only on days 1 and 2 did not have any significant change in their megakaryocyte number. These results implied that committed megakaryocyte precursors were more sensitive to inhibition by increased platelet levels than pluripotential stem cells. Further experiments with plethoric animals indicated that different levels of erythropoietin did not account for the effects of platelet hypertransfusion. The findings could be explained by inhibition of cell proliferation or of differentiation of megakaryocyte precursors by increased platelet levels.

Animals↗
PubMed1975

Effects of vincristine on normal and stimulated megakaryocytopoiesis in the rat.

Vincristine was given to rats in which thrombocytopoiesis was either normal or acutely or chronically stimulated by injections of heterologous antiplatelet serum. A single dose of 0.3 mg/kg was given intravenously. The drug produced an early and a delayed megakaryocytopenia suggesting that it was toxic to differentiated megakaryocytes as well as to proliferating stem cells. The results support the hypothesis that vincristine-induced thrombocytosis may be due to homeostatic adjustments which, in turn, are activated as a result of drug-induced cytotoxicity.

Animals↗