The Journal of clinical investigation
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Patients with chronic uremia develop neurologic defects which are similar to the demyelinating lesions seen in thiamine deficiency. The present study describes inhibitory effects of uremic material on nervous tissue transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway which has been reported to have functional importance in the metabolism of myelinated nervous structures. Transketolase activity (TKA) of normal human brain and spinal cord was measured by the conversion of ribose-5-phosphate (R5P) to sedoheptulose-7-phosphate (S7P). ⋯ Hemodialysis markedly reduced the inhibitory effects of the patients' plasma and the data indicate that uremic patients who received effective long-term dialysis treatment show a parallel decline of transketolase inhibition and uremic neuropathy. The findings demonstrate that in patients with chronic renal failure, low molecular weight factors accumulate and inhibit nervous tissue transketolase. This biochemical defect-uncorrectable by thiamine but reversible by dialysis-may interfere with the metabolism of myelin-supporting cells, and/or of the axonal metabolism of medullated structures, and may thus contribute to the degeneration of myelinated nerves seen with uremic neuropathy.
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The mechanism of cholestasis (decreased bile flow) induced by taurolithocholate in the isolated perfused hamster liver was investigated. Taurocholate was infused to maintain bile acid output, and sulfobromophthalein (BSP) was administered to establish a BSP transport maximum in bile. The effects of taurolithocholate on bile flow and on the biliary secretion of BSP and bile acid anions were determined. ⋯ A substantial fraction (75%) of basal bile flow in the isolated hamster liver was estimated to be independent of bile acid secretion. Cholestasis occurred after taurolithocholate, whereas bile acid secretion was maintained. The results indicate that the most likely mechanism for acute cholestasis induced by taurolithocholate in isolated hamster liver was interference with the bile acid-independent fraction of canalicular or ductular bile flow or both.
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Deposition and clearance of inhaled particles of iron oxide labeled with (198)Au were studied in 19 normal subjects (10 nonsmokers and 9 smokers). For this purpose, monodisperse aerosols of particles with a 2 mu diameter were produced in a spinning disc atomizer. Thoracic counts and images with a scintillation camera were begun immediately after inhalation of the aerosol and continued for 6 hr. ⋯ In smokers, tracheobronchial clearance was delayed for periods of 1-4 hr after inhalation. Furthermore, in contrast with the findings in nonsmokers, significant clearance was still occurring in many of the smokers in the 5th and 6th hr after inhalation. Also, photoscintigrams showed an abnormal accumulation of particles in the large airways several hours after inhalation of the aerosol.
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Plasma lipoprotein alterations in nine insulin-dependent diabetics with hyperlipemia have been related to the lipid accumulating in eruptive xanthomas evolving in these patients. Histochemical and electron microscopic examination of xanthomas have been correlated with the lipid analyses in order to obtain additional evidence regarding the lipoprotein origin of lipids accumulating in the lesions. Both analytical and morphologic evidence suggested that circulating chylomicrons significantly contribute to the xanthoma lipids. ⋯ Initiation of appropriate therapy resulted in clearance of the chylomicronemia and a concomitant resolution of the xanthomas as reflected by a decrease in total xanthoma lipid. Sequential studies of resolving xanthomas in five patients revealed that xanthoma triglyceride was mobilized more rapidly than cholesterol, resulting in a redistribution of the xanthoma lipids, so that the resolving lesions were cholesterol rich. Consistent with this change in lipid composition, correlative electron microscopy revealed loss of amorphous material from many of the foam cell vacuoles.
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Dilute whole blood clots were prepared by addition of thrombin to blood diluted 1:10 in phosphate buffer. The pH of this buffer was 7.4 and the ionic strength was 0.084. Though the ionic strength was low, there was no hemolysis of red corpuscles due to the contribution to the osmotic gradient by plasma salts and proteins. ⋯ Reconstitution of inactivated serum with purified C4, 3, and 5 and thrombin restored its capacity to induce aggregation and retraction of platelets. Therefore, we postulated that platelet aggregation and retraction were necessary for clot retraction and that platelet aggregation and clot retraction facilitated clot lysis. More specifically we postulated that thrombin, in addition to catalyzing clot formation, also modified the platelet membrane such that gammaM globulin (cold agglutinin) and complement components can act on the platelet membrane leading to (a) aggregation and retraction of the platelets, (b) retraction of the clot, and (c) to the activation of plasminogen either on the surface of the platelet by C8i and (or) by release of platelet activators of plasminogen.