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Biomedical subjects

F C Monette

Publications and source records attributed to F C Monette.

At least 37 records · Page 2Linked to original sources

The in vitro erythropoietin sensitivity of late erythroid progenitors subjected to opposing physiologic demands.

The in vitro sensitivity of marrow CFU(E) to erythropoietin was assessed in normal, regenerating, and plethoric marrow and correlated to the cell-cycle distribution of the cells. Although all marrow samples demonstrated a approximately 75% S-phase distribution, regenerating, but not plethoric marrow, exhibited a 5- to 10-fold greater requirement for erythropoietin in vitro. It is concluded that altered responsiveness to erythropoietin may occur independently of alterations in the CFU(E) cell cycle. Secondly, alterations in erythropoietin sensitivity occur under conditions of marrow regeneration but not polycythemic suppression.

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Cell-cycle properties and proliferation kinetics of late erythroid progenitors in murine bone marrow.

The cell-cycle properties of marrow CFUE were assessed in normal regenerating cell preparations. In addition, the erythropoietin sensitivity of CFUE was correlated to the cell-cycle distribution of these cells. The results suggest a coupling of erythropoietin sensitivity to the S-phase of the CFUE cell cycle in so far as CFUE in G2/M/G1 were 2 to 10 times less sensitive to the hormone. It is concluded that the CFUE cell cycle per se is not a focus for erythropoietic regulation.

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Antibodies against pluripotent stem cells: their use in studying stem cell function.

The biologic characteristics and specificity of rabbit anti-mouse brain (RAMB) serum for pluripotent hemopoietic stem cells (CFU-s) is reviewed. The application of RAMB serum to the functional analysis of stem cell differentiation and self renewal characteristics is discussed. Preliminary data are presented which suggest the existence of two stem cell subcompartments. The majority of stem cells express membrane determinants that are detected by RAMB serum. A minor (5%-10%) stem cell subpopulation lacks the stem cell antigen and exhibits a greater self-renewal capacity than those cells expressing the antigen.

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The relationship between stem cell seeding efficiency and position in cell cycle.

The seeding efficiency of colony-forming cells from normal, regenerating and velocity-sedimented cycling and non-cycling narrow preparations was compared. Colony-forming cells in cycle were found to exhibit a 50% reduction in splenic seeding when compared to normal marrow or sedimented non-cycling cells. The results of this study indicate that the spleen colony assay underestimates the total number of colony-forming cells by a fraction which is directly related to the number of cells in cycle.

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Characterization of the anti-stem cell activity of anti-mouse brain serum.

The anti-stem cell activity of a high-titer rabbit anti-mouse brain serum preparation has been further characterized. Following absorption with bone marrow and erythrocytes the antiserum had dose-dependent cytotoxicity against pluripotent stem cells. Rigorous absorptions with bone marrow, spleen, liver, erythrocytes, and thymus failed to remove the anti-stem cell activity of the serum. Adult brain, the immunogen, but not neonatal brain, removed a substantial amount of the activity against stem cells. Maximal cytotoxicity occurred both with and without complement and was maximal following only a 4 degrees C incubation of cells with serum. The anti-stem cell activity was present in the serum globulin fraction. No increase in the frequency of microcolonies or, with longer growth periods, in splenic macrocolonies was observed, suggesting that CFU-s were completely inactivated by exposure to the antiserum. Injected antiserum also reduced CFU-s in vivo.

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Hydroxyurea-induced erythroid differentiation.

Hydroxyurea, a cytotoxic agent which destroys cells in DNA synthesis, has been shown to evoke the differentiation of a small number of hemopoietic precursor cells in the erythroid series of erythropoietically suppressed hypertransfused mice. This effect does not appear to be mediated by erythropoietin (EP) since the simultaneous injection of anti-EP did not alter this response.

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Erythropoiesis in the rat: differential rates of DNA synthesis and cell proliferation.

Direct in vivo estimates of DNA synthesis time in early and late erythroblasts were obtained by using the H(3)- and C(14)-thymidine double-la-beling technique. A double-emulsion autoradiographic procedure was used to resolve the two isotopes. Early erythroblasts were found to proliferate at a rate about five times that of late cells. This results primarily from a shorter mean DNA synthesis time in early cells (2.5 hours) than in late cells (6.5 hours).

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