Search PubMed⌕ Search

Biomedical subjects

D C Dale

Publications and source records attributed to D C Dale.

At least 145 records · Page 8Linked to original sources
PubMed1975

The effect of Hydrocortisone on the kinetics of normal human lymphocytes.

Lymphocyte kinetic studies employing 51-chromium-labeled autologous lymphocytes were performed in nine normal volunteers in order to determine the effects of hydrocortisone administration on the recirculating versus the nonrecirculating intravascular lymphocyte pools. Following infusion of labeled cells, the recirculating portion of the labeled cells rapidly equilibrated with the total intravascular lymphocyte pool and the vastly larger total-body recirculating lymphocyte pool, so that by 1 hr following infusion 21.8% plus or minus 3.2% of the labeled lymphocytes were left in the circulation. Four hundred milligrams of intravenous hydrocortisone administered 24 hr after infusion of labeled cells caused a profound but transient lymphocytopenia which was maximal at 4 hr with return of lymphocyte counts to normal by 24 hr after injection. Concomitant with the lymphocytopenia there was a dramatic increase in lymphocyte specific activity (cpm per 10-6 lymphocytes), while the total lymphocyte-associated radioactivity remaining in the circulation was unchanged, indicating that corticosteroid administration depleted the unlabeled recirculating cells. As the lymphocyte counts returned to normal following hydrocortisone, the specific activity also returned to normal. These studies indicated that hydrocortisone administration caused a transient lymphocytopenia by a preferential depletion of the recirculating portion of the intravascular lymphocyte pool

Adult↗
PubMed1975

Defective polymorphonuclear leukocyte metabolism and function in canine cyclic neutropenia.

Humans and grey collie dogs with cyclic neutropenia are known to suffer from an increased rate of bacterial infection. Because of the previously described microanatomic abnormalities of lysosome formation found in the polymorphonuclear leukocytes (PMNs) of dogs with canine cyclic neutropenia, studies of these cells were undertaken. PMNs from grey collie dogs were found to have significant metabolic and functional abnormalities when compared with normal collie PMNs. These included abnormally increased postphagocytic C1-glucose oxidation, decreased iodination of trichloroacetic acid-precipitable protein in the resting and phagocytizing state, decreased levels of intracellular myeloperoxidase,and a bactericidal defect against a variety of bacteria. Phagocytosis was normal. These abnormalities appear to differ from those previously described in the PMNs of patients with chronic granulomatous disease of childhood and the Chediak-Higashi syndrome and more closely resemble those seen in hereditary myeloperoxidase deficiency. Thus, the studies reported here demonstrate defective PMN function in a disease state previously believed to be a model only of periodic hematopoiesis.

Agranulocytosis↗
PubMed1974

Transplantation of allogenic bone marrow in canine cyclic neutropenia.

Transplantation of normal bone marrow cells to a gray collie dog with cyclic neutropenia resulted in normal granulocytopoiesis. The finding suggests that cyclic neutropenia occurs because the hematopoietic stem cells are defective. Because of the similarity of human and canine cyclic neutropenia, it also suggests that the human disease may be curable by marrow transplantation.

Agranulocytosis↗
PubMed1974

The effect of in vivo hydrocortisone on subpopulations of human lymphocytes.

This study was designed to determine the effect of in vivo hydrocortisone on subpopulations of lymphoid cells in normal humans. Subjects received a single intravenous dose of either 100 mg or 400 mg of hydrocortisone, and blood was drawn at hourly intervals for 6 h, and then again at 10 and 24 h after injection. Profound decreases in absolute numbers of circulating lymphocytes and monocytes occurred at 4-6 h after both 100 mg and 400 mg of hydrocortisone. Counts returned to normal by 24 h. The relative proportion of circulating thymus-derived lymphocytes as measured by the sheep red blood cell rosette assay decreased maximally by 4 h and returned to base line 24 h after hydrocortisone. There was a selective depletion of functional subpopulations of lymphocytes as represented by differential effects on in vitro stimulation with various mitogens and antigens. Phytohaemagglutinin response was relatively unaffected, while responses to concanavalin A were significantly diminished. Responses to pokeweed mitogen were unaffected by 100 mg of hydrocortisone, but greatly diminished by 400 mg of hydrocortisone. In vitro responses to the antigens streptokinase-streptodornase and tetanus toxoid were markedly diminished by in vivo hydrocortisone. Reconstitution of monocyte-depleted cultures with autologous monocytes partially corrected the diminished response to antigens. This transient selective depletion of monocytes and subsets of human lymphocytes by a single dose of hydrocortisone is most compatible with a redistribution of these cells out of the circulation into other body compartments.

Adult↗
PubMed1974

Granulocyte transfusion therapy of experimental Pseudomonas pneumonia.

Pseudomonas pneumonia was produced in dogs with radiation-induced leukopenia. Treatment of this infection with either gentamicin alone or gentamicin plus daily granulocyte transfusion was compared in a randomized controlled trail. The dogs receiving granulocytes plus gentamicin survived significantly longer than those treated with gentamicin alone (P < 0.05). The Pseudomonas immunotype which was inoculated into the dogs were recovered at autopsy from none of the granulocyte-transfused dogs, whereas seven or eight of the dogs treated with gentamicin alone had the inoculated Pseudomonas immunotype in the area of induced pneumonia at autopsy. As measured by the limulus test, the granulocyte-transfused dogs also did not have endotoxemia as frequently as the dogs given only gentamicin (P < 0.05). This controlled study establishes that transfused granulocytes can favorably alter the course of experimental Pseudomonas pneumonia and suggests that granulocyte transfusion may be a useful therapy in serious bacterial infections of leukopenic subjects.

Animals↗
PubMed1974

Hematopoiesis in the grey collie dog: studies of the regulation of erythropoiesis.

Hematopoiesis in the grey collie dog undergoes periodic fluctuations which involve reticulocytes, granulocytes, platelets, lymphocytes, and monocytes. This syndrome is inherited in an autosomal recessive manner and can be transmitted or abolished by appropriate bone marrow transplantation experiments, thus demonstrating this to be a primary marrow defect. Investigation of humoral regulation in this setting indicates that serum erythropoietin (ESF) also undergoes cyclic fluctuation and that shortly after the increase and peak in serum ESF levels recognizable red cell precursors appear in the marrow. Erythropoiesis in the grey collie is reciprocally related to the blood O2 carrying capacity. With phlebotomy, ESF activity and reticulocytes increase but continue to cycle, while hypertransfusion eliminates reticulocyte production completely. Neither phlebotomy nor hypertransfusion alter the underlying cycle time (11-12 days) nor influence the peaks of peripheral blood granulocytes. Thus, in these experiments, no direct evidence of competition between reticulocyte and granulocyte production is observed. In vitro studies of canine hemoglobin synthesis fail to demonstrate evidence of an inhibitor to ESF. These results indicate that periodic fluctuation of serum ESF is an integral part of the grey collie syndrome and are most consistent with some form of feedback regulation of ESF production.

Animals↗
PubMed1973

Periodic hematopoiesis in human cyclic neutropenia.

Human cyclic neutropenia is characterized by severe depression of blood neutrophil levels approximately every 21 days. To investigate the mechanism of cyclic neutropenia four patients were studied with daily complete blood counts, serial bone marrow examinations, marrow reserve testing, serum muramidase determinations, DF(22)P granulocytokinetic studies, and, in one patient, in vivo [(3)H]TdR labeling. Periodogram analysis of the serial blood counts in the latter patient and visual inspection of multiple cycles in the others revealed periodic fluctuations in the levels of blood neutrophils, monocytes, lymphocytes, reticulocytes, and platelets. Rhythmic changes in the morphologic and radioisotopic studies as well as the marrow reserve tests and muramidase measurements were consonant with a mechanism of periodic failure of marrow production rather than peripheral destruction. Human cyclic neutropenia is analogous to cyclic neutropenia in the grey collie dog and may be viewed as the consequence of cyclic hematopoiesis.

Agranulocytosis↗