The Journal of clinical investigation
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Comparative Study
An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats.
For many years it has been thought that distal nephron hydrogen ion secretion can be importantly modulated by factors such as sodium delivery, sodium avidity, and potassium stores. Free flow micropuncture studies have also indicated that the rate of bicarbonate delivery may also alter the rate of bicarbonate reabsorption. The present studies were undertaken to examine possible luminal influences on total CO2 reabsorption in microperfused distal tubules in the rat in vivo. ⋯ Distal tubules of rats with normal acid-base status had JtCO2 values which were neither significantly different from zero nor correlated with changes in JK and JNa. Further, doubling the load from 250-500 pmol/min (by doubling the perfusion rate of 25-mM HCO3 solutions) did not stimulate JtCO2 in these normal animals. Accordingly, these acute in vivo microperfusion studies indicate for the first time that neither load nor potassium or sodium fluxes are important modulators of distal tubule bicarbonate reabsorption.
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Comparative Study
Enhanced alveolar macrophage-mediated antigen-induced T-lymphocyte proliferation in sarcoidosis.
Expansion of T-lymphocyte numbers is a characteristic feature of the alveolitis of pulmonary sarcoidosis. One mechanism that may influence the numbers of T-lymphocytes in the lung is the process of antigen presentation in which alveolar macrophages, in the presence of antigen, induce T-lymphocytes to replicate. To evaluate this process in sarcoidosis, alveolar macrophages were obtained by bronchoalveolar lavage, pulsed with tetanus toxoid, and co-cultured with purified autologous T cells. ⋯ One possible explanation for augmented antigen presentation seen in sarcoid is that an increased percentage of sarcoid alveolar macrophages express HLA-DR or HLA-DS surface antigens. However, most normal and sarcoid alveolar macrophages express HLA-DR and HLA-DS surface antigens, and the percentage of macrophages expressing these antigens was not significantly different in the two groups. Thus, while the mechanisms of the enhanced antigen presentation in the sarcoid lung are unknown, the process of antigen-driven, alveolar macrophage-modulated lung T cell proliferation may explain, at least in part, the expansion of lung T-lymphocyte numbers that characterizes this disease.
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Elastin is an extracellular matrix protein critical to the normal structure and function of human lung. Recently reported data indicate that live human alveolar macrophages can degrade purified elastin in vitro. In this study, we directly compared the elastolytic activity of alveolar macrophages with that of human neutrophils. ⋯ The function of the two pathways depends on the relative excess or deficiency of soluble inhibitors. At inflammatory sites rich in proteinase inhibitors, tissue macrophages may degrade more extracellular matrix elastin than neutrophils. In smokers without antiproteinase deficiency, pulmonary macrophages, which are known to be increased in number, may be the more important cause of elastin breakdown and emphysema.
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During renal ischemia, ATP is degraded to hypoxanthine. When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radical (O-2) is generated. We studied the role of O-2 and its reduction product OH X in mediating renal injury after ischemia. ⋯ In summary, the oxygen free radical scavengers SOD and DMTU, and allopurinol, which inhibits free radical generation, protected renal function after ischemia. Reperfusion after ischemia resulted in lipid peroxidation; SOD decreased lipid peroxidation in cortical mitochondria after renal ischemia and reflow. We concluded that restoration of oxygen supply to ischemic kidney results in the production of oxygen free radicals, which causes renal injury by lipid peroxidation.
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The effects of alternating cycle lengths (bigeminal rhythm) on His-Purkinje system refractoriness were studied in 14 patients using His bundle and right bundle recordings. Programmed atrial stimulation at constant cycle length (method I) was scanned using the atrial extrastimulus technique (A2) and compared with an atrial cycle length of identical duration coupled to A2 on alternate beats (method II). The results showed that (a) despite shorter cycle length of the His-Purkinje system with method II due to effect of A2 on atrioventricular nodal conduction (699 +/- 90 vs. 743 +/- 87 ms, P less than 0.001), the relative refractory period of the His-Purkinje system was always longer with method II (463 +/- 52 vs. 440 +/- 43 ms, P less than 0.001). ⋯ During method II this resulted in shortening of the subsequent right bundle cycle length relative to the subsequent His bundle (and of necessity left bundle) cycle length. The finding of increased His-Purkinje system refractoriness despite shorter preceding cycle length of the His-Purkinje system during atrial bigeminy has never been previously described and suggests that classical concepts of His-Purkinje system behavior may require revision in this setting. Secondly, during atrial bigeminy the occurrence of alternating functional bundle branch block cannot be accounted for solely by the degree of abbreviation of His-Purkinje system cycle length, but may be explained by a relative shortening of the next ipsilateral bundle branch cycle length in the bundle manifesting block.