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Biomedical subjects

D Howard

Publications and source records attributed to D Howard.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1976

The effects of acute bleeding on acid-base balance erythropoietin (Ep) production and in vivo P50 in the rat.

The mechanism of erythropoietin (Ep) production after acute haemorrhage has been thought to be due to a reduction in blood volume and tissue perfusion leading to tissue hypoxia. In the present study we have evaluated the effect of acute haemorrhage in the rat on the acid-base status, the red cell affinity for oxygen in vivo, and Ep production. Within a few hours after acute blood loss there was a respiratory alkalosis with an increase in blood pH, a decrease in pCO2 and an increase in the red cell affinity of Hb for oxygen in vivo that was temporally related to an increase in Ep production. Within 24 h after the acute haemorrhage, the blood pH AND PCO2, red cell affinity for oxygen in vivo, and Ep level returned towards normal. The decrease in in vivo red cell affinity for oxygen was associated with an increase in red cell 2,3-DPG levels and a decrease in Ep production.

Acid-Base Imbalance↗
PubMed1976

Erythroid differentiation of fetal, newborn and adult haemopoietic stem cells.

Erythroid regeneration was studied in lethally irradiated mice given transplants containing equivalent numbers of haemopoietic stem cells (i.e. CFU) from fetal liver, neonatal marrow or adult marrow. Adult marrow was taken from normal control mice, whose CFU for the most part were not in active cell cycle, as well as from phenylhydrazine-treated groups whose CFU were in similar state of proliferation (i.e. approximately 40-50% in DNA SYNTHESIS) AS THOSE DERIVED FROM FETAL LIVER AND NEONATAL MARROW. Splenic and femoral radioiron (59Fe) incorporation were measured at intervals after transplantation and were found to begin earliest in mice given fetal liver, then in animals given neonatal marrow and latest in recipients of adult marrow. Peripheral reticulocytes showed a similar pattern of recovery. The data reported herein suggest that the differences in erythroid regeneration evoked by transplants of fetal liver, neonatal marrow or adult marrow, are not solely attributed to the degree of proliferation in the pluripotential stem cell compartment. These data may, however, suggest a shorter doubling time for cells comprising the fetal and newborn committed erythroid compartments.

Animals↗
PubMed1976

Fetal hemopoiesis in diffusion chamber cultures. III. The effect of neutropenia.

Proliferation and differentiation of granulocytes, macrophages, and both myeloid committed (CFC) and pluripotent (CFU) stem cells in diffusion chamber (DC) cultures of fetal liver were studied in order to evaluate the role of circulating humoral factors in the control of fetal myelopoiesis. When DC with fetal liver cells were implanted into mice rendered neutropenic by pretreatment with cyclophosphamide, more granulocytes and CFC were produced through day 10 as compared to DC implanted into saline pretreated control hosts. A difference in CFU recovery from fetal liver suspensions grown in DC implanted into neutropenic and control hosts was not seen until day 10. Serum CSF concentrations were increased in neutropenic as compared to control host mice 2 and 3 days after implantation of DC. Levels of serum inhibitors of colony growth showed marked variability but, in general, were similar in both groups. These data provide evidence that fetal CFC and fetal myelopoiesis are influenced by a circulating humoral factor present in neutropenic serum. CSF may be the factor, although the data presented in this paper do not establish this with any certainty.

Agranulocytosis↗
PubMed1976

Effect of a congenital defect in hemopoiesis on myeloid growth and the stem cell (CFU) in an in vivo culture system.

W/Wv mice with congenitally defective CFU proliferation and their normal, congenic littermates were used as hosts for diffusion chamber (DC) implants. CFU growth in implanted allogenic CF1, or congenic +/+ marrow was significantly greater in W/Wv than in control hosts. When W/Wv mice were "cured" of their hemopoietic defect, CFU proliferation in the DCs decreased, but not to the control level. These observations have provided evidence for humoral control of CFU growth related to a genetic stem cell defect. Diffusion chamber myelopoiesis was also enhanced in W/Wv hosts. In comparison with their congenic controls, W/Wv mice were neutropenic and had decreased numbers of marrow myeloid elements. Thus, a humorally mediated feedback related to a defective myelopoiesis in the hosts might have accounted for increased DC myelopoiesis. However, a "spillover" effect from increased stem cell growth has not been excluded.

Anemia, Macrocytic↗
PubMed1976

Fetal hemopoiesis in diffusion chamber cultures. I. The pattern of pluripotent stem cell growth.

The growth pattern of fetal liver (FL), normal adult bone marrow (NABM) and regenerating (post Velban treatment) adult bone marrow (RABM) colony forming units (CFU) cultured in diffusion chambers (DC) was studied. When twenty CFU were implanted into DC the recovery of CFU after 4 days with FL, NABM or RABM was 133 +/- 7, 19 +/- 2 and 34 +/- 2 CFU, respectively. The transplantation fraction of CFU from NABM decreased from 10-4% on day 0 to 6-9% on day 4; that of FL did not change from the initial 6-2%. The growth rate of CFU derived from FL was substantially greater than that from NABM. The relative growth of FL and RABM CFU was clearly inhibited when the concentration of cells cultured was increased. Spleen colonies from FL cells before culture were larger (P less than 0-005) than colonies from NABM but after 7 days of culture there was no difference between the two groups. Histological examination of spleen colonies showed that after DC culture FL and NABM CFU were differentiating along the three normal pathways. These data suggest that intrinsic differences exist between fetal and adult stem cells in the in vivo diffusion chamber culture system.

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↗
PubMed1975

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.

Animals↗