First implantation of a 16-channel electric stimulation device in the human body.
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Biomedical subjects
Publications and source records attributed to H Kern.
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The carboxylic ionophores monensin and nigericin, at concentrations higher than 10 and 6 muM, respectively, prevent the penetration of the Semliki Forest virus (SFV) genome into the cytosol of baby hamster kidney (BHK-21) cells and thereby inhibit viral replication. In the absence of inhibitors, the entry of SFV is known to proceed by adsorptive endocytosis in coated vesicles, followed by acid-triggered membrane fusion in intracellular vacuoles or lysosomes. The results show that binding of the virus to the cell surface, adsorptive endocytosis, and intracellular transport of viruses to the lysosomes are only marginally affected by the ionophores. No direct virucidal effect is observed, nor is the membrane fusion activity of the virus at low pH directly affected. Sequential addition of monensin and ammonium chloride (a non-related lysosomotropic inhibitor of SFV entry) indicates that both inhibitors affect the same step in the entry pathway. On the basis of these data and the known effects of carboxylic ionophores and lysosomotropic weak bases on cellular pH gradients, we conclude that monensin inhibits penetration by increasing the pH in endocytic vacuoles and lysosomes above pH 6, which is the pH threshold for the viral membrane fusion activity.
Using a combination of differential centrifugation and free flow electrophoresis (Harms, E., Kern, H., and Schneider, J. A. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 6139-6143) a single population of highly purified lysosomes was obtained from normal, I-cell disease type 1, and I-cell disease type 2 cultured fibroblasts. Our findings indicate that most of the residual acid hydrolase activities remaining within the I-cell fibroblasts are localized in the lysosomes, analogous to normal cells. Characterization of the carbohydrate-dependent properties of the lysosomal N-acetyl-beta-D-hexosaminidase revealed that the I-cell and normal enzymes do not contain a significant proportion of neuraminidase-susceptible sialic acid residues, interact poorly with the beta-galactose-specific lectin Ricinus communis and are highly sensitive to endohexosaminidase H treatment, indicating that the oligosaccharide units of both the I-cell and normal lysosomal N-acetyl-beta-D-hexosaminidase are predominantly of the high mannose type. The I-cell and normal lysosomal N-acetyl-beta-D-hexosaminidase, however, differed in their endocytotic properties. In contrast to the high rate of endocytosis of the normal lysosomal enzyme (7.8%/mg/h), the I-cell type 1 lysosomal enzyme failed to be endocytosed into Sandhoff cells indicating an absent or altered phosphohexyl recognition marker on the I-cell enzyme. Examination of the normal extracellular N-acetyl-beta-D-hexosaminidase revealed the presence of predominantly high mannose-type oligosaccharide units, similar to the corresponding lysosomal enzyme, although properties typical of complex-type oligosaccharide chains were also evident. In contrast, the secreted I-cell enzyme revealed the presence of oligosaccharide units predominantly of the complex type indicating that the I-cell N-acetyl-beta-D-hexosaminidase has had high mannose-type oligosaccharide chains modified to complex-type probably in the Golgi or GERL region prior to secretion from the cell.
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Human diploid fibroblasts underwent lysis when resuspended in isotonic sucrose. After preparation of a granular fraction by differential centrifugation, lysosomes were almost completely purified by free-flow electrophoresis. Electron micrographs of the final fraction of fibroblast lysosomes (about 25-fold purified) showed mostly secondary lysosomes having an appearance identical to those in intact cells. There was no indication that the purification steps selectd for any lysosomal subpopulation. The lysomal nature of the isolated organelles was confirmed by cytochemical staining for acid beta-glycerophosphatase. As judged by a 92% structure-linked latency of beta-N-acetylglucosaminidase in the final fraction, the structural integrity of the isolated lysosomes was unaffected by the purification procedure.
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In 817 patients who were subjected both to X-ray examination and endoscopy of the stomach, the diagnosis was verified histologically. The radiological findings were confirmed in 86% of the cases and the results of endoscopy were verified in 89% of cases. The diagnosis of gastric ulcer was confirmed by X-rays in 87% of cases, by endoscopy in 95%. 88% of the malignant tumours of the stomach were discovered on X-ray examination and 89% through endoscopy. The diagnostic results of X-ray examination to detect carcinoma of the gastric stump or of an anastomosis were somewhat poorer. With optimal technique the results of radiodiagnostic examination are hardly inferior to those of endoscopy. There are advantages and disadvantages inherent in both techniques but they are of a different nature so that the two methods are by no means competitive; indeed, they are complementary and a combination of both methods yields maximum results. X-ray examination offers considerable advantages if it is carried out before endoscopy.
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In contrary to the wild strain, a monocaryotic mutant of Coprinus cinereus (basidiomycete) does not contain hydrosoluble, complex-bound sterols. Under nystatine-treatment, however, the mutant is induced to produce this kind of stereols in abundance. Furthermore, nystatine highly increases sporulation of the mutant and decreases sporulation of the wild strain.
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