Induction of tolerance to allogeneic kidney grafts in irradiated reconstituted adult rats.
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Biomedical subjects
Publications and source records attributed to T Moran.
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A proliferation-competent adult rat liver cell monolayer system has been analyzed for tissue-specific functions during its growth cycle. High levels of the adult (L type) form of pyruvate kinase (EC 2.7.1.40) and glutathione S-transferase B ("ligand," EC 2.5.1.18) are observed during the early lag phase; they decline markedly during the logarithmic phase and reappear during the stationary phase. By contrast, elevated levels of the fetal (K type) form of pyruvate kinase and alpha1-fetoprotein production appear only after proliferation begins; this pattern diminishes slightly during stationary phase as the adult phenotype is restored. Albumin production continues throughout the entire growth cycle. These in vitro findings simulate those observed during hepatoproliferative transitions in the intact animal and, as such, constitute a developmental program for normal epithelial cells in primary culture.
Primary monolayer fetal and adult rat hepatocyte culture systems, which are being used to help analyze in vivo mechanisms controlling liver regeneration, proliferation, and differentiation are described. With results from animal studies of normal or genetically altered rats subjected to partial hepatectomy, to chemical infusions, or to specific dietary deficiency regimens, an apparently complex growth regulatory pattern has emerged. The data suggest a working hypothesis postulating interactions among hormone, nutritional, lipoprotein, and novel nucleotide factors at multiple regulatory sites. These findings may provide some conceptual and experimental basis for future research regarding the development of hepatic cancer, as it may arise spontaneously or from exposure to environmental carcinogens.
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In rhesus monkeys with knife cuts which disconnected the ventromedial hypothalamus and produced hypothalamic hyperphagia, we have studied a variety of stimuli known to reduce food intake: weight gain, emotionally arousing stimuli, bitter-tasting food, amphetamine, and pre-prandial intragastric infusion of nutrient. We demonstrate that these animals are similar to animals with ventromedial lesions in passing through a "dynamic" phase of overeating and weight gain and then stabilizing their body weight at a new level by reducing their feeding in a "static" phase. These animals are also more sensitive to the inhibitory effects of noise and bad taste in food. They, however, are less sensitive to the anorexic action of amphetamine. These results suggest that the ventromedial region is not crucial for the inhibitions produced by emotional arousal under our experimental conditions, but plays some role in amphetamine anorexia. Amphetamine is likely to have some specific anorexic action beyond its potential for arousal, since the same animals which are sensitive to the inhibitory effects of arousal are also resistant to amphetamine. Finally these hyperphagic animals do not differ from intact controls in the reduction of food intake produced by preloading with intragastric nutrient. This result is not consistent with the concepts that hypothalamic hyperphagia is caused by a disruption of satiety and that the ventromedial hypothalmic region is a crucial "satiety" centre.
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Idiotypic vaccines are discussed in relation to those produced conventionally or those which are genetically engineered. The potential value of antiidiotypic antibodies as vaccines has been demonstrated in various animal models of infectious agents. These antibodies represent a heterogenous population: those which bear an internal image of the antigen and those which do not. These groups are discussed in terms of their immunochemical properties, relative frequencies and efficacy as vaccines. The infectious diseases in which antiidiotypic vaccines would be most useful are discussed, as well as problems which may be encountered in the use of such vaccines in humans. Some solutions to these problems are envisaged and an ideal idiotype vaccine is described.