Effective erythropoiesis induced by 5beta-pregnane-3beta-hydroxy-20-one in squirrel monkeys.
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The erythropoietic effect of 5beta-pregnane-3beta-hydroxy-20-one, a naturally occurring steroid metabolite of progesterone, was evaluated in the squirrel monkey by ferrokinetic studies. red cell survival, and blood volume measurements. The intramuscular administration of this steroid in pharmacologic doses shortened the (59)Fe plasma clearance and increased the plasma iron turnover, thereby indicating an increase in erythropoiesis. A normal (59)Fe red cell uptake was observed, and the bone marrow maturation time was not altered. Red cell survival was the same in the treated and control groups. After five weekly injections of the steroid, the monkeys increased their red cell mass by 57%. A significant increase in white blood cells and a slight elevation of platelet counts in the treated monkeys also suggest a possible direct stimulation of hemopoietic stem cells by the steroid metabolite. These observations indicate that some steroid metabolites can stimulate an early increase in iron turnover (within 48 h) that is not secondary to hemolysis. The increased red cell mass indicates effective erythropoiesis in primates. (+info)
Erythrocyte glucose-6-phosphate dehydrogenase and glutathione deficiency in sheep.
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Erythrocytes of 145 sheep representing six breeds were assayed for glucose-6-phosphate dehydrogenase. All sheep had erythrocyte glucose-6-phosphate dehydrogenase values similar to glucose-6-phosphate dehydrogenase deficient erythrocytes of man. Mean erythrocyte glucose-6-phosphate dehydrogenase levels ranged from 0.65 to 1.54 micromoles of reduced nicotinamide adenine dinucleotide phosphate per gram of hemoglobin per minute. Many of these sheep also had low levels and/or unstable reduced glutathione. Sheep with low levels of erythrocyte glucose-6-phosphate dehydrogenase and reduced glutathione were given large doses of oxidizing drugs or fed fresh fava beans to determine if they would develop intravascular hemolysis. No significant hemolysis was detected as a result of drug administration or fava bean ingestion. (+info)
51-chromium labeled erythrocyte half-time disappearance from miniature swine.
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Half-time disappearance of (51)Cr-laeled erythrocytes was studied in 39 Sinclair miniature swine at 20 to 46 days of age and again at 79 to 109 days of age. Mean erythrocyte half-time disappearance, disregarding age, was 21.29 (+/-0.77) days for males and 22.04 (+/-0.81) days for females. The half-time difference between males and females was not statistically significant (P<0.05). At 20 to 46 days of age the mean erythrocyte half-time disappearance was 19.56 (+/-1.41) days. The same pigs, tested at 79 to 109 days of age, had a mean erythrocyte half-time disappearance of 23.95 (+/-1.94) days. There was a significant difference (P<0.01) in erythrocyte half-time disappearance from miniature swine as the result of age and also for age within sex. The grand mean erythrocyte half-time disappearance, for all the miniature swine tested, was 21.67 (+/-0.54) days. The estimate of heritability was 0.61 for dam effect at 20 to 46 days of age and 0.06 at 79 to 109 days of age. Sire estimate of heritability was 0 at both age groups. It was concluded that the large heritability coefficient found only for dam component in young nursing pigs was the result of maternal environment rather than additive genetic variance. (+info)
Half-time disappearance of (51)Cr-labeled erythrocytes from 20 adult miniature swine was measured. Seven males and 13 females from 388 to 418 days of age, having a mean weight of 55kg were studied. Five ml of blood collected from each animal were labeled with 75 microCi (51)Cr at room temperature for 60 to 90 min. Following injection of the labeled erythrocytes into each animal, blood samples were collected every four to six days. Specific activity was measured and half-time disappearance determined by linear regression. The results were compared with values obtained from the same animals tested at two earlier ages. No significant (P <0.05) difference in erythrocyte half-time disappearance was detected between males and females at the three different ages. Mean (+/-SEM) erythrocyte half-time disappearance values were: 20 to 46 days of age, 19.58 (+/-0.59) days; 79 to 109 days of age, 23.56 (+/-1.18) days; and 388 to 418 days of age, 22.35 (+/-0.72) days. A significant (P <0.01) difference in erythrocyte half-time disappearance was found between the miniature swine tested at 20 to 46 days of age and those tested at either 79 to 109 or 388 to 418 days of age. No significant (P <0.05) difference in erythrocyte half-time disappearance was found between the two older age groups. (+info)
Immunopathologic studies in relapsing polychondritis.
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Serial studies have been performed on three patients with relapsing polychondritis in an attempt to define a potential immunopathologic role for degradation constituents of cartilage in the causation and/or perpetuation of the inflammation observed. Crude proteoglycan preparations derived by disruptive and differential centrifugation techniques from human costal cartilage, intact chondrocytes grown as monolayers, their homogenates and products of synthesis provided antigenic material for investigation. Circulating antibody to such antigens could not be detected by immunodiffusion, hemagglutination, immunofluorescence or complement mediated chondrocyte cytotoxicity as assessed by (51)Cr release. Similarly, radiolabeled incorporation studies attempting to detect de novo synthesis of such antibody by circulating peripheral blood lymphocytes as assessed by radioimmunodiffusion, immune absorption to neuraminidase treated and untreated chondrocytes and immune coprecipitation were negative. Delayed hypersensitivity to cartilage constituents was studied by peripheral lymphocyte transformation employing [(3)H]thymidine incorporation and the release of macrophage aggregation factor. Positive results were obtained which correlated with periods of overt disease activity. Similar results were observed in patients with classical rheumatoid arthritis manifesting destructive articular changes. This study suggests that cartilage antigenic components may facilitate perpetuation of cartilage inflammation by cellular immune mechanisms. (+info)
Differentiation of thymus-derived cells from precursors in mouse bone marrow.
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An experimental model system was developed to study the differentiation of thymus-derived (T) cells from progenitors in bone marrow. In this system transplantation of bone marrow cells depleted of T cells gave rise to T cells in the spleens of irradiated recipients within 15 days of transplantation. Thus, normal bone marrow contains a class of cells that are progeniotrs of T cells (PT cells). PT cells are different from T cells since PT cells are incapable of responding to alloantigen, are theta resistant, and band in a lighter density region than do T cells. The density profile of PT cells is different from that of hematopoietic stem cells (CFU-S); PT cells band in a denser region of the gradient than do CFU-S. (+info)
Cell-mediated lympholysis. Importance of serologically defined H-2 regions.
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The cell-mediated lympholytic capability of mouse spleen cells stimulated in mixed lymphocyte culture is related to the major histocompatibility complex genotype on target lymphocytes. The strain combinations AQR-B10. T(6R) and B10.A(4R)-B10.A(2R) that result in significant mixed lymphocyte culture activation do not mediate cell-mediated lympholysis on sensitizing target lymphocytes; serologically defined regions (H-2K and H-2D) are identical within each combination. H-2K or H-2D region disparity alone does not cause cell-mediated lympholysis. However after mixed lymphocyte culture activation as seen with B10.A-B10.T(6R), a target cell bearing only an H-2K region difference from the effector cell is sensitive to cell-mediated lympholysis. Likewise an H-2D region difference is an adequate target after mixed lymphocyte culture activation of the effector cell in the combination B10.A(2R)-B10.D2. (+info)
Synergism between subpopulations of thymus-derived cells mediating the proliferative and effector phases of the mixed lymphocyte reaction.
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The mixed lymphocyte reaction is characterized by proliferation and generation of specifically cytotoxic effector lymphocytes. These two phases of the mixed lymphocyte reaction have been shown to be mediated by distinct subpopulations of thymus-derived cells. The current investigation demonstrates that combinations of cells from thymus and lymph nodes of CBA mice exhibit synergism with respect to proliferation and effector cell production in response to Balb/c alloantigens. That is, the magnitude of the proliferative and effector phases of the mixed lymphocyte reaction exhibited by combinations of thymus cells and lymph node cells was greater than that given by equal numbers of the two cell types cultured separately. This cooperative interaction between lymphoid cell subpopulations in the mixed lymphocyte reaction parallels that which is responsible for the graftversus-host reaction. It is proposed, therefore, that the mixed lymphocyte reaction provides an in vitro model for the study of in vivo thymus cell interactions occurring in the graft-versus-host reaction. (+info)