A method for leukokinetic study in the nonsteady state.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C R Bishop.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The mechanism by which adrenocortical steroids induce granulocytosis in man has been investigated using granulocytes labeled with radioactive diisopropylfluorophosphate. After an intravenous injection of 200 mg of cortisol was given to five normal subjects, the mean value for the total blood granulocyte pool increased from 79 to 138 x 10(7) cells per kg of body weight and reflected an increase in the size of both the circulating granulocyte pool and the marginal granulocyte pool. When granulocytes in the circulation were labeled with diisopropylfluorophosphate and granulocytosis was induced later by the intravenous administration of cortisol, the rate of decline of granulocyte specific activity was increased, indicating that the blood pool was being diluted at an accelerated rate by unlabeled cells entering from the bone marrow. The rate of egress of granulocytes from the blood pool to an inflammatory exudate was studied by the "skin window" technique. After the administration of cortisol, there was a mean reduction in the cellularity of induced inflammatory exudates of 75%. However, this reduction in cellularity varied considerably from subject to subject (45-98%). From these studies we can infer that steroids induce an absolute granulocytosis by decreasing the rate of egress of cells from the total blood granulocyte pool as well as by increasing the influx of cells from the bone marrow. By model simulation studies of the non-steady state induced by cortisol injection, it has been possible to quantitate these rate changes. In the present studies cortisol injection resulted in a mean decrease in blood granulocyte egress of 74% (1-99%) and a mean increase in cell inflow of 450% (300-750%).
Data pertaining to the endogenous mouse spleen colony system, 10 days postirradiation, are presented. The D(o) for visible colonies is 78 R, while that for 6 hr iron uptake over a range of 600-800 R is 50 R. The D(o) for spleen weight is 196 R and that for IUdR uptake is 193 R. These measurements increase with the age of the mouse. Hypertransfusion decreases spleen iron uptake and colony number. DF-(32)P and sodium sulfate-(35)S are not useful indicators of splenic hematopoiesis in this system. Visible hematopoietic colonies in the spleen are not produced by vinblastine, nitrogen mustard, methotrexate, or cyclophosphamide.
Normal dog plasma and serum, human, rat, and Swiss-Webster mouse plasma, phytohemagglutinin, sheep red cells, mumps and influenza vaccine, fibrinogen, and endotoxin injected before irradiation led to an increased number of endogenously derived spleen colonies in irradiated mice. Spleen weight and uptake of radioactive iron and iododeoxyuridine into such spleens were also increased. The relationship between these parameters of splenic hematopoiesis was unchanged by plasma injection suggesting that, while the number of colonies was increased, the composition of individual colonies was unchanged. This conclusion was supported by studies on plethoric mice in which splenic erythropoiesis is abolished. Increased splenic hematopoiesis was accompanied by an increase in the volume of packed red blood cells 10 days after irradiation. The total volume of plasma injected, the number of days of plasma injection preceding irradiation, and the route of administration were all important variables influencing the effect of plasma injections. Crude fractions of human albumin and gamma globulin, cortisol, C57BL (maternal) and DBA (paternal) mouse plasma, and isogeneic plasma were without effect. The ineffectiveness of isogeneic and closely related allogeneic plasma rendered unlikely the hypothesis that this effect represented the presence of homeostatic hematopoietic regulating factors in plasma. The increased hematopoiesis induced with plasma appeared to be limited to the spleen, for increased bone marrow hematopoiesis was not detected. Certain observations suggested that the effect of plasma may not be due to an antigenic or an inflammatory effect. From current observations, it was unclear whether the increased colonies induced by plasma were representative of expansion of the colony-forming cell pool or of increased efficiency of growth of the fraction surviving irradiation.
Explore the source record for details and available documents.