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Biomedical subjects

C D Dunn

Publications and source records attributed to C D Dunn.

At least 55 records · Page 3Linked to original sources
PubMed1980

Investigations into the in vitro sensitivity to erythropoietin of haematopoietic tissue from ex-hypoxic, erythrocytotic mice.

If 'sensitivity' is defined as the ratio of haem synthesis in erythropoietin (Ep)-stimulated cultures to that in cultures without added Ep, then haematopoietic tissue of ex-hypoxic mice is less sensitive to Ep in vitro than similar tissue from normal donors. This appears to be due primarily to the loss of erythropoietin responsive cells from the marrow and spleen. In addition, saline extracts of mature erythrocytes inhibited erythropoiesis in normal bone marrow cultures in a manner directly related to the 'haematocrits' used during their preparation. These data support recent suggestions that the preference of erythrocytotic mice over normal animals for Ep assay probably can be attributed to their low baseline level of erythropoiesis rather than an increased sensitivity to Ep.

Animals↗
PubMed1980

Effect of food or water restriction on erythropoiesis in mice: relevance to "anemia" of space flight.

Dehydrated mice showed a negative energy balance and hemoconcentration similar to that thought to occur in men during space flight, although the mechanism producing these changes may be completely different. The relative importance of dehydration and a negative energy balance in producing erythroid suppression has been investigated. The initial suppression appeared to be due to a reduced food intake. Thereafter, this negative energy balance produced about 40% of the erythroid suppression, the severity of which was augmented by dehydration. The decreased food consumption appeared to suppress erythropoiesis by reducing the sensitivity of the target cells in the spleen to erythropoietin (Ep), the erythropoietic hormone. Hemoconcentration decreased titers of Ep thus also suppressing erythropoiesis. Attempts to alleviate the effects of water deprivation and reduced food consumption by effects of water deprivation and reduced food consumption by water injections and the feeding of supplemented diets were only marginally effective at ameliorating the erythroid suppression. These studies indicate the importance of maintaining an adequate energy and fluid balance in the regulation of erythropoiesis.

Animals↗
PubMed1980

Regulation of erythropoiesis in diabetes mellitus.

The regulation of erythropoiesis in 40 subjects with diabetes mellitus was investigated to test the hypothesis that increased blood concentrations of glycosylated hemoglobin would produce a reduced p50 and a compensatory increase in erythropoietin. Little evidence to support this hypothesis was observed. However, diabetes did produce complex changes in hemoglobin-oxygen releasing capacity which were compensated for in the expected way, i.e. oxygen releasing capacity showed an inverse correlation with erythropoietin. We conclude that the effects of diabetes on erythropoiesis are minor and probably have no pathological significance in most patients suffering from this disease.

Adolescent↗
PubMed1980

The ultrastructural immunocytochemical demonstration of erythropoietin receptors on developing erythrocytic cells of fetal mouse liver.

In spite of the severe restrictions imposed by the lack of high purity erythropoietin (Ep) and Ep specific antiserum wer have attempted to demonstrate presumptive Ep binding sites on the surface of developmental forms of erythrocytic cells of the mouse fetal liver using ultrastructural immunocytochemical methodology. Cells were exposed to exogenous Ep of differing potencies and concentrations and subsequently incubated in an Ep antiserum. The Ep-Ep-antiserum complex was then visualized with a gold-labeled IgG reagent. Limited surface labeling was noted on the developing erythrocytic cells and the evaluation of the mean surface labeling densities of the erythrocytic cell series indicated that the extent of labeling was related to the stage of maturation. Early polychromatophilic erythroblasts proved to be the most heavily labeled of the erythrocytic cells followed by the basophilic erythroblast, proerythroblast and late polychromatophilic erythroblasts respectively; normoblasts, reticulocytes and erythrocytes exhibited, at most, only minimal labeling. In addition, we have been able to demonstrate several primitive cells in the fetal liver which exhibited extensive surface labeling when compared with the developing erythrocytic cells. These cells may represent the erythroid precursors of the fetal liver.

Animals↗
PubMed1980

Erythropoietin assays: some new and different approaches.

Published reports of the levels of erythropoietin (Ep) in normal human serum have been reviewed. Current evidence suggests that the level of Ep in normal human serum is 30 +/- 10 mU Ep/ml. When serum was concentrated before assay somewhat lower values were obtained and the mouse fetal liver cell assay gave slightly higher values. Three new potential Ep assay techniques are presented. These are: 1) The use of synthetic microbeads as indicators in an agglutination assay, 2) the use of wheat germ lectin in affinoelectrophoresis techniques, and 3) an immunoradiometric assay as an alternative to radioimmunoassays. The results indicate that the use of all three assays should be explored further.

Anemia, Aplastic↗
PubMed1980

Animal & computer investigations into the murine erythroid response to chronic hypoxia.

During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their progenitors from the medullary cavity. The changes in CFU-E were preceded 48-72 hours earlier by an increase in serum erythropoietin (Ep) titers which, in turn, had been preceded by a rapid and marked "shift-to-the-right" in the hemoglobin oxygen dissociation curve. During hypoxia, the mice lost a considerable fraction of their body weight. Computer simulations, using a mathematical model of erythropoietic regulation, suggest that this weight loss, either indirectly by reducing the need for red cells in a smaller-than-control animal or by directly altering the sensitivity of the Ep-producing mechanism, is the major cause of the falling Ep titers despite continuation of the hypoxic stress. Because of high endogenous 59Fe incorporation levels, it was not possible to confirm the thesis that animals with an expanded Erythropoietin Responsive Cell (ERC) compartment would be more sensitive to exogenous erythropoietin than are mice with a normal or reduced ERC population.

Animals↗
PubMed1980

Humoral regulation of erythropoiesis in cats: preliminary report.

Cats were subjected to acute or subacute phlebotomy regimens in a study to investigate the humoral regulation of erythropoiesis as mediated by erythropoietin. The erythropoietic effects of the acute phlebotomy regimen were similar to those effects of the subacute regimen. serum erythropoietin in cats was increased for at least 10 days after initiating the phlebotomies.

Animals↗
PubMed1980

The effect of dehydration on erythroid progenitor cells in mice.

Mice deprived of water for three days showed hemoconcentration due to a reduced plasma volume, suppressed erythropoiesis and reduced food intake. All three classes of erythroid progenitor cells in both the bone marrow and spleen of dehydrated mice were markedly suppressed but recovered rapidly upon rehydration. In addition, during dehydration the spleen cellularity was significantly decreased and was associated with an increase in the percentage of adherent cells. The changes in erythroid progenitor cells during dehydration are compared to previously published data on changes in these cell populations in erythrocytotic mice with similar hematocrits. This comparison indicates that, as we have suggested earlier, the major component producing the erythroid suppression in dehydrated mice is the reduced food intake. Hemoconcentration plays a minor role. The relevance of these changes to the "anemia of spaceflight" is discussed.

Animals↗
PubMed1980

Methods for the measurement of multiple parameters of erythroid regulation within individual mice.

Hematocrit, hemoglobin p50, percent reticulocytes, rate of erythropoiesis using 59Fe, and blood volume were determined in individual mice using a single blood sample. Furthermore, sufficient blood remained to provide a serum pool from no more than five mice for an erythropoietin assay. These multiple procedures did not interfere with one another, and the various measurements did not need to be made immediately. Freshly prepared 51Cr-labeled erythrocytes were, however, required for blood volume determinants.

Animals↗
PubMed1979

Some immunological and haematological aspects of human cyclic neutropenia.

In addition to standard peripheral blood cell counts, sequential studies have been made of changes in the T-lymphocyte population and in the serum titres of the presumptive humoral regulators of haematopoiesis, Colony Stimulating Activity (CSA) and Erythroid Stimulating Activity (ESA), in a young woman with cyclic neutropenia (CN). In addition, serum immunoglobulins, C3 and total complement levels and serum protein concentrations were determined on several occasions during the study. Similar tests were done concomitantly on a haematologically normal, age and sex-matched control. Cell counts on peripheral blood from the subject with CN demonstrated a clearly defined periodicity in neutrophil and monocyte concentrations and equivocal fluctuations in reticulocyte numbers. There was no evidence of periodicity in the lymphocyte concentrations and the T-lymphocyte population appeared functionally normal. Spontaneous incorporation of tritiated thymidine into peripheral blood cells showed a highly significant correlation with the monocyte count, suggesting that these cells were responsible for the radioisotope uptake. CSA titres were elevated on all occasions tested and showed no evidence of periodicity. ESA showed some evidence of cycling with elevated levels being observed during the periods of neutropenia. Serum complement levels were within the normal range but all classes of immunoglobulins were elevated and albumin levels were depressed.

Adult↗
PubMed1979

Thyroid hormones and protein synthesis in fetal mouse liver erythroid cells.

Hemoglobin synthesis represents an important step in the maturation of the developing erythron. In this study, we determined the effect of various thyroid hormones and analogs upon globin synthesis by fetal mouse liver erythroid cells. Globin synthesis was stimulated in 13--15 day fetal liver erythroid cells, whereas cells, whereas cells from 17 day fetuses were unresponsive. There was no correlation between stimulation of globin synthesis and reported calorigenic activity of the various hormones assayed.

Animals↗
PubMed1979

The in vitro growth of erythroid colonies from dog bone marrow.

Enriched methyl cellulose media together with either human urinary erythropoietin or serum collected from phlebotomized dogs exposed to hypoxia was used in the study of the erythroid colony forming (CFU-E) capacity of dog marrow. The dog serum erythropoietin was found to be more efficient in stimulating CFU-E than comparable concentrations of human urinary erythropoietin. Numbers of CFU-E were directly related to the culture concentration of the stimulating serum and to the number of cells per plate. Sheep plasma erythropoietin was also found to be effective in stimulating CFU-E growth. The system described is chemically better defined and produced more consistent results than has been reported for the plasma clot method.

Animals↗
PubMed1979

Evidence that the fetal mouse liver cell assay detects erythroid regulatory factors (ERF) not measured with a standard in vivo assay.

A simplified modification of the fetal mouse liver cell (FMLC) assay has been used to investigate the relationship between in vivo and in vitro detectable Erythroid Regulatory Factors (ERF) in the serum of dogs exposed to hypoxia. The results suggest that the FMLC assay is a useful technique for following changes in serum ERF. However, the data obtained cannot be directly equated with the in vivo erythrocythemic mouse assay unless a correction factor is applied. This is necessary because the in vitro assay, in general, detects 50% more ERF than does the standard mouse assay.

Animals↗