[Resistance of renal parenchyma to intermittent periods of ischemia. Experimental study].
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Biomedical subjects
Publications and source records attributed to M De Marchi.
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A case of true hermaphroditism with 46, XX/46, XY karyotype is reported. The propositus, reared as a male, showed ambiguous external genitalia with perineoscrotal hypospadias, and internal genitalia represented by bilateral ovotestes, normal uterus and tubes. Periodic menstrual bleedings appeared at puberty. The endocrinologic data demonstrated the secretory activity of both the ovarian and the testicular tissue. The analysis of red cell, lymphocyte and serum markers, done on the propositus and on his parents, failed to show any evidence of double fertilization. On this basis, the origin of the XX/XY condition (mosaicism versus chimerism) and its developmental consequences are discussed.
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Different classes of protease inhibitors and substrates were tested for their effect on the ability of human lymphocytes to mediate antibody-dependent cytotoxicity (Ab CMC). All the inhibitors tested (serine esterase inhibitors, chloromethyl ketone derivatives of tosyl-amino acids, synthetic protease substrates), except for the naturally occurring protease inhibitors (derived from soybean, lima bean, and porcine pancreas), were able to suppress, or to reduce insignificantly, the cytotoxicity. In the absence of a direct demonstration of an esterase activity, sensitive to the action of the inhibitors in the effector lymphocytes, careful controls were used to restrict the possibility that some nonspecific effect of the drugs was being interpreted. Particularly, the dependence of the inhibition of cytotoxicity as an effect of drugs on membrane transport mechanisms or on energy metabolism was excluded. The similarity between results obtained with compounds of different chemical characteristics and different molecular mechanisms of action supports a specific effect of the inhibitor on cellular esterase(s) or possibly protease(s). The fully reversible inhibition obtained with serine esterase inhibitors suggests that the relevant enzymes are activated only after effector-target cell interaction; the irreversible effect of chloromethyl ketone derivatives, however, does not allow the participation of already activated enzymes to be excluded. The results presented in this study on the probable role of cellular esterases, on cation requirement and on the sequence of biochemical steps in Ab CMC add a new element to the analogy between this cellular phenomenon and different types of cytotoxicity or other immunologically induced cellular reactions, suggesting that the biochemical mechanisms of cytotoxicity may partly reflect a common pattern of cellular response to external stimuli.
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Antibody-dependent cytotoxicity mediated by human peripheral lymphocytes is an active energy-requiring phenomenon. In this study the relative importance of glycolysis and respiration was analyzed, by measuring the effect of various metabolic inhibitors (sodium azide, antimycin A, 2-deoxy-D-glucose, iodoacetate), alone or in combination, on effector cell efficiency and intracellular ATP level. The inhibition of both aerobic and anaerobic energy production in the effector cells completely abolished cytotoxicity. An inhibition of 50% was observed when the intracellular ATP concentration was decreased to levels corresponding to 30 to 50% of those in the untreated controls.
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