Spontaneous plaque-forming cells in renal transplant patients: possible correlation with antibody-mediated rejection.
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Biomedical subjects
Publications and source records attributed to T Horsburgh.
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Very small amounts (0.5 to 2 microliters) of H-2-incompatible blood given 16 days before skin grafting led to the induction of a long-lived unresponsiveness when the mice were given a short postoperative course of alternating doses of procarbazine hydrochloride and antilymphocyte serum. This unresponsiveness, which was specific for the blood donor strain, was wholly attributable to the white cell moiety, plasma and red blood cells having proved to be ineffective. The optimal dose range of white blood cells was fairly narrow (7 x 10(3) to 1.4 x 10(4)). Of the various attempts made to demonstrate that the blood inoculum modified the response of normal mice, only direct skin grafting gave a positive result in that the survival of allogeneic skin grafts was curtailed. Mixtures of blood from several mouse strains injected into CBA recipients induced long-term unresponsiveness to skin grafts of the blood donor strains. However, although it was possible to create unresponsiveness to DBA/2, C57Bl, or strain A skin grafts in CBA mice pretreated with blood from a closed colony outbred strain (TO), this pretreatment had no beneficial effect to induce unresponsiveness to TO skin grafts in TO recipients. It is argued that these findings are no necessarily inconsistent with the observation that, in inbred animals, the induction of unresponsiveness was strain specific.
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Cyclosporin A (CS-A) is an unusual endecapeptide isolated from the fungi Cylindrocarpon lucidum Booth and Trichoderma polysporum. It is a potent immunosuppressive drug that prevents rejection of kidney and heart allografts whilst having a low myelotoxicity. Its mode of action is still unclear but its main target appears to be the T lymphocyte. The mixed lymphocyte reaction (MLR) and cell-mediated lymphocytoxicity (CML) used here are generally regarded as in vitro correlates of allograft rejection. Our data show that CS-A is a powerful inhibitor of MLR reactivity, regardless of whether the cells were obtained from normal or presensitized donors; that the CML of lymph node cells is likewise totally inhibited if the drug is added early during cell culture; and that, by contrast, the cytotoxic response of spleen cells from presensitized but not from normal mice is only partially inhibited, even with a tenfold increase in dose. It is therefore suggested that there exists a population of cytotoxic spleen cells that is relatively resistant to the action of this drug.
1. A newly developed biotin assay was used to monitor plasma and urinary biotin concentration after the oral administration of biotin. 2. In two normal subjects, leucocyte propionyl-CoA carboxylase and beta-methylcrotonyl-CoA carboxylase were markedly stimulated after the administration of biotin.
An attempt was made to increase the in vivo immunosuppressive powers of antilymphocyte globulin (ALG) by conjugating it with malphalan (MEL), an alkylating agent, via an inert intermediate carrier (polyglutamic acid). Careful controls to distinguish between increased activity attributable to the conjugate per se, as opposed to synergy between the components of the complex, were included. Conjugation did not destroy the alkylating properties of the drug nor the cytotoxic activity of the antibody. The effect of MEL-ALG complexes on skin allograft survival in both inbred and outbred strains were appraised. In neither system did the immunosuppressive powers of the conjugate exceed those of ALG alone, regardless of the dose used. We conclude that alkylating drugs are not suitable for this particular purpose.
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A sensitive and convenient protein-binding assay for biotin in physiological fluids is described. The method is based upon the binding of an iodinated biotin conjugate by avidin followed by separation of bound and free conjugate by charcoal absorption. Adult plasma biotin levels averaged 1.26 pmol/ml, a value comparable to that determined by microbiological assays for biotin.
1. The synthesis of gamma-glutamylhydroxamate from glutamate and hydroxylamine has been utilized as an approximation of glutamine synthetase activity in kidneys of rabbit, rat, dog, monkey and man. 2. Kidneys of rabbit contain glutamine synthetase in high activity; those of rat, in intermediate activity; and those of dog, monkey and man, in negligible activity. 3. No more enzyme is present in kidneys of the latter two species than in those of the dog, in which the enzyme is generally considered to be absent.
In accord with results of others, we have observed that the infusion of phlorizin at low rates (2.16-117 microgram-kg-1-min-1) progressively increases fractional excretion of glucose from 0.47 to 0.85. Further increasing the rate of infusion to 2.19 mg-kg-1-min-1 increases fractional excretion to 1.0. The relationship appears to describe a single function having characteristics of an adsorption isotherm. The metabolism of the kidney, expressed as rate of total CO2 production from all substrates, is modestly and variably reduced by infusion of phlorizin at both high and low rates. The metabolism of glucose, expressed as rate of CO2 production, is variably but not consistently altered by infusion of phlorizin. The oxidation of [14C]lactate derived from [14C]glucose is negligible and introduces no significant error into measurement of 14CO2 from [14C]glucose. The percent of total CO2 derived from glucose does not differe significantly in control periods from the mean of all periods following phlorizin. Accordingly interaction of phlorizin with peritubular membranes at high rates of infusion, in the sense of blocking penetration of glucose, does not occur. Our methods do not rule out nor do they prove adsorption of phlorizin to these membranes.
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