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Biomedical subjects

C D Dunn

Publications and source records attributed to C D Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1983

Is the stability of the oxyhaemoglobin dissociation curve in stored blood a function of the way the cells 'pack'?

The results in this report show that the oxyhaemoglobin dissociation curve (ODC) of blood when stored at 4 degrees C under special storage conditions was stable for at least 7 days. The stability of the ODC was reflected in both the haemoglobin p50 (the partial pressure of oxygen at 50% saturation of the haemoglobin) and n (the Hill slope of the ODC) values and was associated with constant blood pH and 2,3-diphosphoglyceric acid (2,3-DPG) concentrations. The ODC was stable whether heparin, ethylene diamine tetra-acetic acid (EDTA) or citrate phosphate dextrose (CPD) were used as anticoagulants, but the latter was associated with higher p50 values than those observed in fresh samples. The most critical storage requirement for the ODC stability appeared to be some function of the area of the cell-plasma interface as orientation of the collection tubes in other than a vertical position, or storing blood in larger containers, resulted in a marked fall in p50. These results have important implications in that they suggest that the relative packing of the cells or cell-cell and/or cell-plasma interfaces can significantly affect the ODC stability. Further, they may be of potential importance in blood banking practice.

Blood Preservation↗
PubMed1983

Serum erythropoietin changes in cats with feline leukemia virus-induced erythroid aplasia.

Erythropoietin concentrations were increased significantly (p less than 0.025) in nine cats with natural feline leukemia virus infection and associated erythroid aplasia compared to six clinically normal cats. Adult cats experimentally inoculated with the Kawakami-Theilen isolate of feline leukemia virus developed a progressive simultaneous increase in erythropoietin activity and decrease in packed cell volume. These findings indicate that erythroid aplasia associated with feline leukemia virus infection is not caused by a failure in erythropoietin production.

Anemia, Aplastic↗
PubMed1983

Stomatocytosis in a colony of captive squirrel monkeys (Saimiri sciureus).

Chronic stomatocytosis, which increased in severity as a function of the time that animals were held in captivity, was observed in a small colony of squirrel monkeys. The stomatocytosis was associated with increasing hematocrits possibly due to a change in packing characteristics of the erythrocytes rather than any overt changes in the erythrocyte mass. Reticulocytes remained at control levels throughout development of the stomatocytosis. The most probable cause of this alteration in erythrocyte shape distribution was dietary, but the exact etiology was not determined.

Animals↗
PubMed1983

Erythropoietin bioassays using fetal mouse liver cells: validations and technical improvements.

Studies are described which were designed to compare an erythropoietin (Ep) bioassay using the uptake of 125I-deoxyuridine (125-I-UdR) into whole cells cultured in micro-titer plates with an established method where the cells were cultured in 1 ml volumes using the incorporation of 59Fe into heme as the endpoint. The results demonstrate the validity of the substitution of 125I-UdR uptake into whole cells as a replacement for 59Fe incorporation into heme as an assay endpoint and the adaptation of the method to a semi-micro scale with automated cell harvesting. A culture time significantly shorter than 24 h is demonstrated not to be of practical benefit. Two methods are proposed to saturate the growth promoting effects of iron-containing transferrin. The performance of semi-micro, serum-containing bioassay employing untreated serum as the test material is shown to be superior to previous systems for the biological measurement of Ep.

Animals↗
PubMed1982

An analysis of variance program for the evaluation of results of parallel line assays.

A program is described and illustrated for the one-way analysis of variance of parallel line assays. The procedure involves 4 distinct steps: Data input, either from a previously-prepared data file or by direct 'manual' progression with options to correct input errors; data display, in tabular form, of the results from each specimen after several available transformation options; displays of the analysis of variance table, potency ratio, and confidence limits on the basis of results selected from the data display mode; and, a standard, commercially-available plotting capability of either actual or idealized regression lines. The program provides a rapid, convenient, and accurate procedure, with a high level of operator interaction, with which to perform the somewhat cumbersome mathematical manipulations necessary for the evaluation of parallel line assay results. The availability of this program should overcome one of the problems which frequently prevents the complete analysis and validation of the results of parallel line assays.

Analysis of Variance↗
PubMed1982

Production of presumptive humoral haematopoietic regulators in canine cyclic haematopoiesis.

Conditioned media (CM) were prepared according to previously published techniques from the bone marrow of dogs with cyclic haematopoiesis (CH). CM prepared from day 9 marrows inhibited mouse bone marrow CFU-s proliferation rate while CM from day 10 marrows were stimulatory and also contained an erythroid stimulating factor which appeared to be erythropoietin. In addition a highly significant trend from CM containing CFU-s inhibitory materials to media with CFU-s stimulatory activity was observed through cycles day 1 to 8. These studies further support the concept that CH is due to a defect in factors controlling stem cell proliferation and suggest that a major event occurs in CH dog marrow on days 9 and/or 10 of the cycle.

Animals↗
PubMed1982

Conditions for an in vitro culture of murine mixed hematopoietic colonies and their putative cellular origin.

The supernatant fluid of stimulated spleen cells (PHA-SCM) supported in vitro colony growth of murine marrow. In the absence of exogenous erythropoietin, it stimulated the growth of (1) myeloid colonies and (2) distinct mixed colonies containing erythroid cells, granulocytes, macrophages, and infrequently megakaryocytes in a setting structurally resembling biopsied marrow. The cells that form mixed colonies reside in a density range of 1.058-1.068 g/ml in a discontinuous albumin gradient. Active supernatant was produced by T cells in combination with a macrophage factor. DNA synthesis correlated with activity. PHA-SCM differed from erythropoietin (EPO) when chromatographed on lectin columns and did not contain EPO activity as demonstrated by the fetal mouse liver cell (FMLC) assay. The activity for mixed colony growth could be eluted from an anion exchange column with 0.07 M NaCl and eluted in a gel filtration column at a distance corresponding to a molecular weight of 39,000. Mixed colony-forming cells responsive to PHA-SCM were found to be Ia-H-2+. BFU-Es, CFU-Cs, and progenitors for myeloid colonies responsive to PHA-SCM were also H-2+ but showed significant sensitivity to anti-Ia antisera reflecting variable antigenic density. The mixed colony-forming cell appeared less differentiated than myeloid or erythroid progenitor cells examined, and its antigenic determinants are consistent with those observed for the pluripotent stem cell assayed in vivo (CFU-S).

Animals↗
PubMed1981

Prostaglandins and erythropoiesis: structure/action relationships and identification of the prostaglandin responsive cells.

Ten prostaglandin derivatives have been investigated for their ability to stimulate heme synthesis in serum-free cultures of fetal mouse liver cells in an attempt to define the structural requirements of the prostaglandin molecule necessary for erythrostimulation. In descending order of potency, only PGE2, PGF2 alpha and PGB1 produced at least 50% stimulation of endogenous heme synthesis. Seven of the ten prostaglandin derivatives tested were inhibitory at high concentrations. The PGE2 effect was pharmacologically distinct from that of Ep and could be antagonized by 15 epi PGF2 alpha. Unit gravity cell sedimentation studies demonstrated that PGE2 stimulated only the larger cells within the erythropoietin responsive cell population.

Animals↗
PubMed1981

Psychogenic purpura (autoerythrocyte sensitization).

A 41-year-old woman has had a long history of repeated episodes of recurrent painful ecchymotic lesions. Results of coagulation tests were normal other than a slight decrease in antithrombin III. Skin tests were positive in response to the patient's own washed red cells. Light and electron microscopy of both the spontaneous and the induced lesions showed nonspecific changes but failed to reveal immunologic vasculitis. Psychologic evaluation showed hysterical and masochistic traits, depression, anxiety, and inability to deal appropriately with hostile impulses. Placebo was successful on several occasions in controlling or modifying the severity of the ecchymotic lesions.

Adult↗
PubMed1981

Three commercial immunoradiometric "kit" assays for serum ferritin evaluated.

We evaluated three commercially available immunoradiometric assays for serum ferritin, with particular emphasis on the statistical validity of the results. The data show that it was unusual (a) for dose/response relationships of the standards to be linear over the whole concentration range suggested by the manufacturers and (b) for dose/response relationships of test sera to parallel those of the standards. These findings cast doubt on the ability of any of the assays reliably to discriminate small differences in ferritin concentrations. Nevertheless, all three methods gave reproducible results, but this reflects technical expertise rather than accuracy of the results per se. The method based on liver ferritin as tracer detected less of the iron-binding protein than those based on spleen ferritin, despite significant cross reactivity of the two antibodies.

Evaluation Studies as Topic↗
PubMed1981

Dynamic regulation of erythropoiesis: a computer model of general applicability.

A mathematical model for the control of erythropoiesis has been developed based on the balance between oxygen supply and demand at a renal oxygen detector which in turn controls erythropoietin release and red cell production. Tissue oxygen tension is regulated by adjustments of hemoglobin levels resulting from the output of a renal-bone marrow controller. Special consideration given to the determinants of tissue oxygenation included evaluation of the influence of blood flow, capillary diffusion, oxygen uptake, and oxygen-hemoglobin affinity. A theoretical analysis of the overall control system is presented including: a) dynamic and steady-state responses, b) sensitivity analysis to determine the relative importance of parameters and their influence on model behavior, c) properties of the model as a proportional controller, d) analysis of steady-state errors, and e) effectiveness of feedback regulation. Computer simulations of altitude hypoxia, descent from altitude, red cell infusion, and hemolytic anemia demonstrate the validity of the model for general human application.

Anemia, Hemolytic↗
PubMed1981

Interactions of animal and computer models in investigations of the "anemia" of space flight.

Previous studies in mice deprived of water have suggested that these animals, like men in space, show hemoconcentration due to plasma volume reductions, a weight loss greater than that due to fluid loss alone, and suppression of red blood cell production. To more fully understand the mechanisms responsible for the suppressed erythropoiesis in dehydrated mice, a mathematical model for erythropoietic regulation has been adapted to this rodent. Computer simulations suggested several new experimental studies to more fully understand the erythroid response to dehydration. The investigations were directed to determining whether dehydration was accompanied by: a) a shortened red blood cell survival, b) altered sensitivity of the erythropoietin (Ep)-producing mechanism, c) a shortened red blood cell transit time, d) changes in the Ep serum half-life, e) changes in hemoglobin P50, and f) reduced renal blood flow. All parameters except changes in renal blood flow were investigated in vivo and incorporated into, or omitted from, the mathematical simulations as directed by experimental findings. The mathematical model is able to realistically simulate the in vivo erythroid response to dehydration making only one, experimentally-untested, assumption. Computer simulations confirm conclusions drawn from the animal studies that the primary cause of the suppressed erythropoiesis in dehydrated mice is the reduced food intake, with hemoconcentration playing a relatively minor role. The interaction between computer simulations and animal experiments is shown to be a powerful approach for formulating and testing hypotheses, designing new experiments, and achieving a clearer understanding of the factors controlling erythropoiesis.

Anemia↗