Organizational development through strategic management planning.
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Biomedical subjects
Publications and source records attributed to C Bishop.
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Antisera against the products of the major histocompatibility system (MHS), produced by immunization between congenic mouse strains differing only at that segment of the 17th chromosome rosettes which bears the H-2gene complex, exert a reproducible blocking effect on formation of with EACm (C3d rosettes). In many instances this effect is probably due to specific antibodies reactive with the lymphocytes, as indicated by immunochemical and adsorption experiments. Purified antibodies from the C3H anti-C3H.B10 immune ascites failed to exert this blocking effect. The blocking capacity can be restored, however, by addition of fresh normal mouse, rabbit or fetal calf serum, but not by heat inactivated serum. These experiments show that the presently defined H-2K, H-2D and H-2L antigens as well as some Ia antigens are themselves not the C3d receptors. The blocking effects observed in the presence of complement are possibly due to the proximity of H-2 or Ia molecules and C3d receptors, or to a rearrangement of membrane components after reaction with anti-MHC anti-MHC antibodies and complement.
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H-1-incompatible rat renal allograft survival rates are strongly influenced by the non-major histocompatibility system (MHS) genes. The same H-1 (MHS) incompatibility tested on four different non-MHS backgrounds gave widely differing results ranging from 11 to 60% fractional survival between the best and the poorest (P less than 0.01) at 105 days. These results can best be explained if non-H-1 and intra-MHS amplifiers and/or suppressors are invoked.
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Sera from DBA/2 and Quackenbush mice (which are non-immune for mastocytoma and Sarcoma 180 respectively) contain a heat-labile (56 degrees for 30 min) component(s) that inhibits the in vitro growth of DBA Mastocytoma P-815 X-2 and Sarcoma 180. Adsorption of the sera with tumour cells at 4 degrees did not eliminate the factor(s), suggesting that it is not an antibody. In liquid suspension cultures inhibitory activity was observed at concentrations of mouse serum of 10--20% and in semisolid agar clonogenic cell assays at concentrations as low as 1%. The influences of the inhibitor(s) for both tumours and in both culture systems were parallel. However, there was a quantitative difference in susceptibility to other environmental factors (FCS concentration, bicarbonate concentration, and O2 tension) between the two tumours. These results parallel the in vivo findings where intravenously injected mastocytoma cells produced more tumours than did Sarcoma 180.
The results are presented of two experiments in which the quality of samples of bull semen was assessed by a number of laboratory tests and then correlated with the 112-day non-return percentage obtained by the use of those samples in A.I. The results reveal the inadequacy of the laboratory tests used as methods of predicting the fertility of semen samples but show that limits may be set outside which poor semen samples could be discarded.
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In red blood cells as well as in platelets there appears to be a decrease in adenine nucleotides during storage under blood bank conditions. This can be decreased by use of anticoagulant preservatives with higher phosphate content than the standard ACD solution, through the addition of adenine and inosine. Maintenance of higher ATP levels appears to be related to longer circulating life span after transfusion into patients in the case of red blood cells but not platelets. Inosine and more alkaline preservative medium also contribute to the maintenance of 2,3-DPG levels in red blood cells, and with it to the maintenance of normal hemoglobin dissociation curves and thus oxygen-carrying capacity. Certain nucleoside analogs may contribute to the preservation of platelets and of whole blood by their platelet-aggregation inhibitory activity. Platelet-aggregation inhibitors may also be useful in preventing thromboembolic episodes with potentially greater safety than anticoagulants.
Cholestyramine (Dowex 1-X2), a strongly basic anion-exchange resin, has previously been shown to bind bacterial endotoxin, preventing both its toxicity and intestinal absorption. Because hemoperfusion through charged and uncharged resins is practical, a study was undertaken to test the endotoxin-binding characteristics of a number of resins. The resin to be tested was washed and swelled overnight, and 1 mg/ml of 51Cr-labeled endotoxin was added and the mixture, agitated and incubated at 37 degrees for a specific time period. In the Dowex 1 series, the 1-X2 was superior to the 1-X4 and 1-X8 in its ability to bind E. coli endotoxin, removing about 90% from solution in 15 min. Increasing mesh size seemed to offer more binding sites for each Dowex 1 resin. Activated charcoal adsorbed about 90% of the endotoxin also, but Amberlite XAD-2 showed little binding capacity. Injection of filtrate from unlabeled E. coli and S. typhosa resin-treated solution into rats, demonstrated that both Dowex 1-X2 and activated charcoal prevented the transaminase rise noted in animals injected with solutions not so treated. It is concluded that Dowex 1-X2 resin and activated charcoal efficiently remove endotoxin in vitro, and may offer a unique method for removing circulating endotoxin in vivo.
The Corning 940 Titrator, which measures total calcium concentration by titration with [ethylenebis(oxyethylenenitrilo)]tetraacetic acid, was evaluated for use in hospital laboratory. Calcium values for patients' sera were about 0.3 mg/dl lower as measured with the Titrator than with the Technicon SMA 12/60 continuous-flow analyzer. A similar bias was evident when the results with the Titrator were compared with those from atomic absorption spectrophotometry. Agreement was better in the low range and worse in the high range. Within-day and between-day coefficients of variation on the Titrator were about 1.5% and 2.5%, respectively. We saw no interference from magnesium, phosphorus, bilirubin, or in the presence of lipemia. At extremely increased hemoglobin concentrations (500 mg/dl), there is a 5% inhibition. Titrator results for patients' urine samples correlated closely (n = 0.999) with those obtained with the SMA 12/60.
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Human red cells were incubated at pH 8.2 and 30 mM phosphate concentration with glucose, glucose plus methylene blue, or inosine. In 16 normal subjects, the lactate production rate (LPR) from glucose alone was 92.2 +/- 7.5 mumoles per minute per liter red blood cell. With methylene blue added, the mean LPR was 118.5 +/- 7.4 per cent of control glucose values. With inosine as substrate the mean LPR was 68.5 +/- 6.0 per cent of that from glucose. Lactate/glucose ratios averaged 1.36, presumably because of accumulation of intermediates under conditions of high pH and Pi. Patients with various kinds of anemias had LPR's from glucose that were usually markedly higher than normal, but the LPR's from inosine were generally about 2/3 of those from glucose. The LPR's of the anemic patients correlated with their degree of reticulocytosis and several patients with pyruvate kinase (PK) deficiency showed normal LPR if the red cell population age was ignored, byt marked depression when compared to expected LPR for degree of reticulocytosis. The LPR from glucose of red cells of G6PD-deficient subjects was decreased (not increased) by methylene blue. Methylene blue, while stimulating the pentose phosphate pathway, also mediated some oxidation of NADH, thus complicating the stoichiometry of the overall system. In addition, the results suggested that the dye may have attacked -SH groups on some enzymes. In normal red cells, the lower LPR from inosine than from glucose was explained as due to consumption of ATP for hexose utilization (thus generating more ADP for the triose reactions). In confirmation, when red cells were incubated without substrate to deplete their ATP-, and enhance their ADP-, levels, the LPR from inosine exceeded that from glucose. Fluoride and iodoacetate affected LPR from glucose more than from inosine, suggesting the necessity of adequate ATP levels in hexose utilization. Overall glycolysis in the red cell is seen as the resultant of a network of metabolic reactions in which ADP and ATP levels are important control parameters.
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