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C D Dunn

Publications and source records attributed to C D Dunn.

At least 91 records · Page 5Linked to original sources
PubMed1976

Changes in erythropoiesis and renal ultrastructure during exposure of mice to hypoxia.

During hypoxia, elevated ESF levels occur which are accompanied by increased erythropoietic activity resulting in progressive elevation of the haemoglobin and haematocrit concentration. An attempt has been made to correlate ultrastructural changes in the kidney with changes in serum ESF concentrations and the erythropoietic state of mice exposed to continuous hypoxia for 3 weeks. A series of changes in the epitheloid and proximal tubules cells occurred which may be related to the biogenesis of erythropoietin. However, no detectable ESF or renal erythropoietic factor could be extracted from the kidneys at the time of maximal ultrastructural changes. Although some ESF-inhibitory material was demonstrated, it could not be extracted into lipid solvents. It is suggested that the failure to consistently extract an erythropoietic factor from the kidneys of hypoxic mice may be related to the absence of renal storage at the onset of increased peripheral demand. Other levels and durations of hypoxia may help to elucidate the role of the kidneys in regulating serum ESF levels.

Animals↗
PubMed1976

Histological alterations in spleen and bone marrow colonies produced by irradiation of the donor mice.

The previously reported decrease in the ratio of erythrocytic (E): granulocytic (G) spleen colonies observed 8 days after bone marrow transplantation, when the donors had been x-irradiated up to 4 hours before the marrow was taken for transfer, was confirmed. The effect of taking the marrow between 4 hours and 13 days after x-irradiation, on the E:G ratio in both spleen and femoral bone marrow colonies, has been studied in detail. The reversion to a normal E:G ratio in spleen colonies assessed at 8 or 10 days was associated with increases in this ratio of colonies in the femoral bone marrow. Transplantation of cell suspensions prepared from the spleen and femoral bone marrow of primary recipients 8 days after the initial transfer produced a histological distribution of 8-day colonies in secondary recipients which was indpendent of x-irradiation of the donor. The data suggest that a hypothesis involving CFU migration within the spleen and, possibly, from the bone marrow to the spleen, provides a more satisfactory explanation of the data than one involving two CFU populations with different radiosensitivities.

Animals↗
PubMed1976

The influence of steroids on erythropoiesis in mouse fetal liver cell cultures: relevance of cell cycle state.

It has been shown that erythropoietin-mediated stimulation of heme synthesis in mouse fetal liver cells in vitro is correlated with hydroxyurea sensitivity. Assuming that OHU is specifically cytotoxic for cells in DNA synthesis this suggests that erythropoietin sensitivity may be related to this phase of the cell cycle. The direct effects of 19-nortestosterone and 3beta-hydroxy-5beta-pregnan-20-one on heme synthesis correlated with the capacity of these steroids to initiate DNA synthesis. It is suggested that the ability of these steroids to increase the proportion of cells in the Ep-sensitive phase of the cell cycle is probably the mechanism responsible for the erythropoietic effects of these agents. 17beta-hydroxy-5alpha-androstan-3-one appears to have a different mode of action since it has only minimal effects on heme synthesis and did not increase hydroxyurea sensitivity.

Androstanes↗
PubMed1975

Sex-determined antigens in rats detected by bone marrow transplantation but not skin grafting.

Skin grafting in untreated rats and bone marrow transplantation into minimally immunosuppressed recipients have been used to investigate histocompatibility differences associated with the Y chromosome. Male skin survived for upwards of 120 days with no sign of rejection when grafted into female rats in circumstances where male bone marrow was rejected. Y chromosome-associated antigens were only detected with skin grafting by prior exposure of the female rats to male cells. It is concluded that bone marrow grafting into minimally immunosuppressed recipients may provide a more sensitive index of minor histocompatibility differences than skin grafting. The need to recognise donor cells in recipients prepared for bone marrow grafting with cytotoxic chemicals is emphasized.

Animals↗
PubMed1975

A quantitative bioassay for erythropoietin using mouse fetal liver cells.

The conditions under which mouse fetal liver cells in vitro are most sensitive to erythropoietin have been investigated with the object of establishing a rapid and sensitive bioassay for this hormone. Fetal liver age and incubation times are shown to be relatively unimportant. Of the commercially available media studied, Eagles Minimal Essential Medium plus 5 percent Fetal Calf Serum is superior to other media used to study erythropoiesis in mouse fetal liver cells. The number of cells per 1 ml culture is important since some evidence was obtained for cell cooperation occurring above 10-6 cells per culture. To minimize this possibility 5 x 10-5 cells are used. If (59Fe) ferric citrate is used to assess heme synthesis, no significant advantage is observed by prior binding of the isotope to mouse serum transferrin. Butan-2-one is preferred to cyclohexanone for extracting heme. Using the conditions described in this report the mouse fetal liver cell assay for erythropoietin is capable of detecting erythropoietin concentrations as low as 0.001 unit culture. Preliminary results using normal human sera show that it is sufficiently sensitive to detect erythropoietin over a range of serum concentrations. This allows a full dose-response relationship to the sera to be determined and, by a comparison with an erythropoietin standard, detailed quantitative results can be obtained. Therefore the technique seems to fulfill the need for a rapid and sensitive erythropoietin bioassay for routine clinical use.

Animals↗
PubMed1975

An evaluation of factors affecting the in vitro bioassay for erythropoietin.

Two main aspects of the in vitro mouse foetal liver cell assay for Erythroid Stimulating Factor (ESF) in human sera have been investigated. The haem extraction process has been shown to give specific and quantitative recovery of 59Fe labelled haem from haemoglobin thus confirming that the material assayed in human sera is stimulating the synthesis of this protein. The extraction procedure can be simplified considerably by prior mixing of the reagents without significantly influencing the results. Several serum constituents (citrate, testosterone, B12, folic acid and iron) have been investigated over a range of concentrations for possible effects on the cultures. Generally only small effects on haem synthesis were observed. It is concluded that variations in the levels of these factors in sera from treated patients will not produce any significant alterations in the estimated ESF concentrations.

Animals↗