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Ferrokinetic studies were performed in three copper-deficient swine and the results have been compared with similar studies in 18 normal pigs. The mean value for the plasma iron turnover rate in the deficient swine was 1.76 mg./kg. day; for the red cell iron incorporation rate, 1.24 mg./kg. day; for the red cell iron turnover rate, 1.18 mg./kg. day; for the red cell life span, 13 days. Corresponding figures in the normal swine were 1.11 mg./kg. day, 1.01 mg./kg. day, 0.59 mg./kg. day and 63 days, respectively. The red cell life span was measured by the use of radioactive chromium in a total of 26 pigs. The mean erythrocyte half-life of normal cells transfused into normal pigs was 17 days. The mean half-life of erythrocytes from copperdeficient swine transfused into copper-deficient swine was 9 days. The mean half-life of red cells from control animals transfused into copper-deficient swine was 16 days while that of erythrocytes from copper-deficient swine transfused into normal pigs, was 13 days. The mean half-life of cells from iron-deficient pigs transfused into iron-deficient pigs was 19 days. It is concluded that copper deficiency anemia results from both a shortened erythrocyte survival time and limited capacity of the bone marrow to produce red cells. It is suggested that copper is an essential component of erythrocytes in swine.

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.

Mice were irradiated repetitively at 6 wk intervals. The proliferative capacity of the hematopoietic stem cell compartment was studied after each irradiation and compared to that of age-matched controls which had been irradiated only once. Hematopoietic proliferation capacity was measured by determining the number of spleen colonies, splenic iron uptake, spleen weight, and volume of packed red cells 10 days after irradiation. 6 wk after the first irradiation, the hematopoietic compartment was apparently supranormal in size for, when such mice were again irradiated, their postirradiation hematopoiesis was in excess of that of the controls. Thereafter, there was a steady decline in regenerative capacity with each sequential irradiation. After the sixth irradiation, the number of spleen colonies and iron uptake were reduced to one-fifth of that of singly irradiated controls. A decline in body weight and an increase in irradiation mortality accompanied the decline in postirradiation hematopoiesis. The degree of measured decline in hematopoietic proliferative ability was less than that observed by other investigators who studied the effect of serial transplantation of cells upon their ability to proliferate. Furthermore, even after the sixth irradiation, a marked stimulation of postirradiation hematopoiesis was induced by bleeding the animals before irradiation.

Ferrokinetic studies were performed on 3 swine given phenylhydrazine, 3 swine deficient in pyridoxine, and 3 swine deficient in pteroylglutamic acid. Body surface radioactivity was measured in 2 pteroylglutamic acid-deficient animals. In the animals given phenylhydrazine, the mean erythrocyte survival time was 5 days. The plasma iron turnover rate was increased about fourfold, and the rate of erythropoiesis was four to five times greater than that in the control pigs. In the pyridoxine-deficient swine, the mean erythrocyte survival time was within the limits of normal. The plasma iron turnover rate was increased fourfold, but the rate of erythropoiesis was approximately one-fourth the normal mean value. These data are interpreted as indicating that the anemia associated with this deficiency is a result of an inability of the bone marrow to produce a normal number of erythrocytes. In the pteroylglutamic acid-deficient swine, the mean erythrocyte survival time was 17 days. The plasma iron turnover rate was 5 times the normal mean value. The rate of erythropoiesis was 1.6 times greater than the mean value in the control pigs. These data are interpreted as indicating that anemia develops in this deficiency as a result of a combination of a shortening of the erythrocyte survival time and a limitation of the capacity of the bone marrow to increase red cell production to the same degree as a normal marrow. The radioactivity in the liver, spleen, and bone marrow of the pteroylglutamic acid-deficient swine, as determined by measurement of the radioactivity over the body surface, declined more slowly than in control pigs.