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Biomedical subjects

C D Dunn

Publications and source records attributed to C D Dunn.

At least 73 records · Page 4Linked to original sources
PubMed1978

Control of hemoglobin synthesis in fetal erythroid cells by L-thyroxine.

Fetal mouse liver cells were incubated in the presence of L-thyroxine, Globin synthesis by cells from the 13th to 15th days of gestation was stimulated by the presence of the hormone. Although protein synthesis by cells from the 17th day of gestation was stimulated, the protein was not identified as globin. A tentative conclusion was drawn that fetal erythroid tissue may be preferentially stimulated by thyroid hormone.

Animals↗
PubMed1978

Production of erythropoietin in vitro: a review.

The in vitro production of the important regulator of erythropoiesis, erythropoietin (Epo), is reviewed. It is concluded that it is possible to produce almost routinely small quantities of Epo in tissue culture. Although such procedures offer the potential to provide large quantities of the hormone for clinical use, the optimum culture conditions and mechanisms for triggering Epo production have yet to be resolved.

Animals↗
PubMed1978

The in vitro production of erythropoietin and thrombopoietin.

In order to determine if there were any relationships between thrombopoietin, erythropoietin and erythrogenin, supernatant fluids from culture lines of foetal mouse liver, foetal and adult bovine kidney, and adult rabbit kidney cells have been assayed for their content of the presumptive humoral regulators of haematopoiesis. Hormone production varied markedly from one culture line to another confirming other studies that the optimal culture conditions for the generation of haematologically-active hormones have not been delineated. The lack of any discernable relationship between the production of thrombopoietin and erythropoietin, thrombopoiet in these and erythrogenin or erythropoietin and erythrogenin suggests that materials represent three distinct entities.

Animals↗
PubMed1978

Separation of erythropoietin responsive cells in fetal mouse liver.

The erythropoietin responsive cells (ERC) in suspension cultures (ERCSC) of fetal mouse liver and the cells producing erythroid colonies in 2-day plasma clot cultures (CFU-E) sediment at similar rates. However, the sedimented fractions containing the majority of nucleated cells show minimal sensivitity to erythropoietin (Ep) and these cells sediment at a slower rate than the ERCSC. The studies suggest that in short-term suspension cultures of fetal mouse liver, Ep acts on morphologically unrecognizable cells to increase the number of hemoglobin-synthesizing cells rather than by increasing the quantity of hemoglobin synthesized per cell. This effect is similar to the principal in vivo action of Ep.

Animals↗
PubMed1978

Technical comments on the bioassay of erythropoietin.

Quantitative erythropoietin determinations can only be obtained after the examination of both Standard and Test materials in a multiple dose parallel line bioassay with appropriate statistical control. The expression of results in erythropoietin units (implying quantitation) in the absence of similar dose-response relationships for Standard and Test materials can lead to errors in the estimated potency which differ markedly from the true potency. Results obtained from one-dose test systems cannot therefore be considered quantitative. Criteria which allow valid quantitation of bioassay results are discussed. Where these cannot be fulfilled, it is suggested that the results should be expressed only in terms of the measured parameter, e.g. 59Fe uptake, per constant volume of test solution.

Animals↗
PubMed1978

Erythroid colony formation in vitro from the marrow of dogs with cyclic hematopoiesis: interrelationship of progenitor cells.

Committed erythroid progenitor cells (Colony Forming Units-Erythroid, CFU-E) have been studied in canine cyclic hematopoiesis (CH) utilizing a semi-solid methyl cellulose culture system. Erythroid colonies were stimulated by the addition of a standard volume of serum from normal dogs that had been phlebotomized and subjected to hypoxia. CFU-E fluctuated over the cycle in dogs with CH from concentrations 4--5 times normal during the periods of peripheral blood neutropenia to less than one tenth of normal during the phases of elevated peripheral blood neutrophil counts. In spite of these marked fluctuations there was no change in the proliferation rate of the CFU-E as estimated by the tritiated thymidine (3H-TdR) suicide technique. Failure to demonstrate a change in the CFU-E proliferation rate may be related to the relative maturity of these cells with the fluctuations in number resulting from a 'feed-in' from more immature cells. The results show that CFU-E fluctuate in the same phase as committed granulocytic progenitor cells (CFU-C). Our current knowledge of the interrelationships of marrow progenitor cells and events in the peripheral blood of dogs with CH is briefly reviewed and some additional questions, raised by recent studies regarding the pathogenesis of this disease, are discussed.

Animals↗
PubMed1978

Erythroid regulatory factors: correlation of detectable titers in vivo and in vitro.

Titers of erythroid regulatory factors (ERF), as measured in vivo with a standard erythrocythemic mouse technique, showed a highly significant correlation with those obtained in vitro with a fetal mouse liver cell (FMLC) assay. The results from the assay in vitro were somewhat higher than would be predicted from the assay in vivo. Nevertheless, the FMLC technique has been found to be a valid and useful technique particularly in the study of serum ERF titers.

Animals↗
PubMed1978

Effect of dehydration on erythropoiesis in mice: relevance to the "anemia" of space flight.

Mice deprived of water for 24 h showed an increase in hematocrit and loss of body weight comparable to that seen in men during space flight. The increase in hematocrit was entirely due to a decrease in plasma volume and was associated with suppression of erythropoiesis, but with no significant change in the serum titer of a presumptive humoral regulator of erythropoiesis, Erythroid Stimulating Activity (ESA). Mice deprived of water for 24 h may be a useful model for the study of the early hematological effects of space flight. The suppression of erythropoiesis due to a relative erythrocytosis appears to be independent of ESA.

Animals↗
PubMed1977

Pathophysiological changes in serum erythropoiesis stimulating activity.

The mouse fetal liver cell bioassay has been used to study serum levels of erythropoiesis stimulating activity (ESA) in patients with a variety of haematological disturbances. The results indicate that this assay system provides a quantitative measurement of ESA, the concentration of which varies predictably in a manner which is consistent with it having a function as an in vivo regulator of erythropoiesis. Dose-response curves for serum ESA show highly significant parallelism with those obtained from sheep plasma erythropoietin and the International Reference Preparation of human urinary erythropoietin.

Anemia↗
PubMed1977

Progenitor cells in canine cyclic hematopoiesis.

Granulocytic (colony-forming units in culture, or CFU-c) and erythrocytic (erythropoietin-responsive cells, or ERC) progenitor cells in canine cyclic hematopoiesis (CH) have been shown to fluctuate over the cycle and in the same phases as one another. The ERC cycle is preceded by 3 or 4 days by a rise in serum erythroid-stimulating activity and is followed by a reticulocytosis. During the cycle CFU-c show a differential sensitivity to two sera, one normal and one containing elevated amounts of colony-stimulating activity. The proliferation rate of CFU-c also fluctuates from well above normal to considerably less than normal over the cycle. These results are discussed in the light of present knowledge of the pathogenesis of canine CH. We suggest that these results support the contention that CH is a disorder of hemopoietic stem cells and that the cycling of humoral factors and peripheral blood cells may follow as a consequence.

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PubMed1977

Oxymetholone and erythropoiesis: failure to detect an effect in fetal mouse liver cell cultures.

Oxymetholone, a steroid of proven clinical value in the treatment of refractory anemia, was without effect on endogenous or erythropoietin-mediated heme synthesis in fetal mouse liver cell cultures. This conclusion applied both when the cells were exposed to oxymetholone prior to culturing with erythropoietin and when the steroid was present in the cultures simultaneously with erythropoietin. Unlike those steroids having a direct effect on erythroid cells, oxymetholone also failed to increase the proportion of erythropoietin responsive cells in DNA synthesis. The relevance of these observations to the therapeutic benefit of oxymetholone is discussed. While the possibility that oxymetholone has to be metabolized to an active form cannot be excluded, the results suggest that oxymetholone does not seem to be erythropoietically active by a direct effect on erythroid cells. The fact that it is a successful therapeutic agent in some patients with aplastic anemia may be due to its proven ability to increase endogenous erythropoietin levels or to reduce ineffective erythropoiesis.

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PubMed1977

The influence of alpha thioglycerol on erythropoiesis in fetal mouse liver cell cultures.

alpha-Thioglycerol has been shown to increase hemoglobin synthesis in suspension cultures of fetal mouse liver cells. The mechanism of this effect is unknown but appears to be directly on S-phase cells increasing their sensitivity to erythropoietin. alpha-Thioglycerol inhibits heme synthesis when S-phase cells have been removed by prior treatment with hydroxyurea. The stimulatory or inhibitory effects of thiols depending on the proportion of cells in S-phase suggests that extreme caution should be used when interpreting cell kinetic studies of cultured cells if thiols are present in the cultures.

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