[Distal radius fracture in the elderly: fixation with Kirchner wire or with gypsum only? Comparative study].
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Biomedical subjects
Publications and source records attributed to H B Burch.
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Glycerol metabolism in 9 defined parts of rat nephron was studied by measurement of glycerol kinase and observation of effects of large glycerol loads on related metabolites and on ATP and total adenylate. Glycerol kinase with glycerol as substrate was highest in the proximal convoluted tubule, slightly lower in straight portions, 20 to 25 times lower in distal segments, and almost indetectable elsewhere. With dihydroxyacetone as substrate, enzyme distribution differed little except for 30% lower activity in proximal convoluted segments. Methods of measurement with 10-40 ng of freeze-dried tissue are described. Glycerol loads produced large accumulations of glycerol 3-phosphate in proximal segments and in distal convoluted tubules. In the control nephron, fructose bisphosphate plus triose phosphates was 1 times higher in distal straight and convoluted segments than in proximal segments. Increases with glycerol loads were limited to proximal straight tubules (2-fold) and the thin limb area (60%). Glucose-6-P increased 3-fold in the late portion of the proximal straight tubule but not elsewhere. ATP and total adenylate were markedly depleted no phosphorylated intermediates accumulated. Levels of Pi were decreased in whole cortex and medullar following glycerol loads.
In a previous study of discrete segments of rat nephron, we reported the levels of high-energy adenylate and guanylate phosphates to be highest in the distal straight and convoluted tubules. Those findings stimulated the study of the distribution of seven enzymes involved in the following metabolic pathways of these nucleotides [Formula: see text]. The patterns of distribution of enzymes in each pathway differed greatly. The phosphodiesterases, 1 and 2, were high in glomeruli and distal tubular segments and low in proximal segments. Adenylate kinase, 3, in contrast, was high in glomeruli, proximal segments, thick ascending limb of Henle, and distal convoluted tubules. Guanylate kinase levels, 4, however, were similar in all segments. The pattern of nucleosidediphosphate kinase, 5, was high in proximal convoluted, thick ascending limb, and distal convoluted tubules. The pattern of the degradative enzyme, 5'-nucleotidase, 6, whose levels were highest in proximal segments, was opposite from that of AMP deaminase, 7, highest in the distal nephrons. These dissimilar patterns underscore the extent of nephron heterogeneity.
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Rats were given large parenteral loads of fructose and the different segments of single nephrons then analyzed for fructose metabolites, fructose metabolizing enzymes, and nucleotide high energy phosphates. Fructokinase and fructose-1-P aldolase activities, and all the major metabolite and nucleotide effects, were confined to the proximal tubule. The proximal straight segment had the highest fructokinase and suffered the greatest changes. In this segment, fructose-1-P rose to 60 mmol/kg (dry weight basis) and glycerol-3-P and glucose-6-P reached 8 and 12 mmol/kg, respectively. ATP fell 80% and GTP (judging from the changes in GTP plus GDP) fell by the same percentage, but UTP was less affected. Total adenylate decreased 50%. In the proximal convoluted tubule, where fructokinase was lower and fructose-1-P aldolase higher than in the straight segment, fructose-1-P rose ony one-fourth as much and glucose-6-P was almost unchanged. In contrast, glycerol-3-P rose more, reaching 16 mmol/kg. Other substances measured along the nephron were glycerol-3-P dehydrogenase, fructose-1,6-bisphosphate aldolase, fructose, glucose, fructose bisphosphate, triose phosphate, and 6-P-gluconate. Control ATP levels were found to be highest in the distal tubule.
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In the adult rat kidney, alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.1) and D-amino acid oxidase (EC 1.4.3.3) were measured in glomeruli, 4 parts of the proximal tubule, 2 parts of the distal tubule and in patches from the thin limb area and the papilla. These enzymes were measured in more limited parts of the nephron during postnatal development. Adult aspartate aminotransferase activities (percentage of the highest) ranged from 100 in the distal straight segment to 25 in the late part of the proximal straight segment to 10 in the thin limb and papillary area. Alanine aminotransferase (lower by a factor of 100 in absolute terms) was distributed as the mirror image of aspartate aminotransferase within proximal and distal tubules. D-Amino acid oxidase was 850-fold higher in proximal straight segments than in medullary structures. During development alanine aminotransferase increased 6-fold and D-amino acid oxidase, 4.5-fold in proximal straight tubules but aspartate aminotransferase increased in distal straight tubles 8-fold.
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Glutamine accumulation in rat kidney was investigated by giving large loads of gluta, mate and aspartate and measuring glutamine changes in seven completely defined portions of the nephron and in small patches from the thin limb area and from the papilla. Both glutamate and aspartate (which is partly coverted to glutamate) caused increases up to sixfold in glutamine which were mainly confined to the proximal straight tubule. Plasma glutamine is minimally affected. In contrast, large glutamine loads doubled plasma glutamine and caused about a doubling of glutamine concentrations in all parts of the nephron, but resulted in no greater change in the proximal straight tubule than elsewhere. Simultaneous inulin and glutamine measurements make it seem likely that the proximal convoluted tubule is a major site of glutamine reabsorption. The low glutamine concentrations in these cells (only 40% higher than that in plasma) indicate a very small gradient at the antiluminal surface. We suggest that the proximal straight tubule is the major site of glutamine synthesis but that it may not be an important site of glutamine breakdown.
Methods were devised or modified which made it possible to measure phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase in seven defined parts of single nephrons and in patches from thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. All three enzymes were essentially confined to the proximal tubule. In normal kidneys, the levels were highest in the proximal convoluted tubule. Glucose-6-phosphatase was 20 times higher in the early part of the convoluted segment than in the late part of the straight segment. With one exception, in acidosis, only phosphoenolpyruvate carboxykinase increased (fourfold in the proximal convoluted segment but much less in the straight portion). In starvation, phosphoenolpyruvate carboxykinase increased about as much as in acidosis in the proximal straight tubule, but not as much in convoluted portions, whereas glucose-6-phosphatase rose modestly in both parts of the proximal tubule and fructose bisphosphatase rose only in the straight tubule, especially the early segment. It is suggested that ammoniagenesis can accompany gluconeogenesis in the proximal convoluted tubule but not in the straight segment.
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The effect of L-methionine-DL-sulfoximine (MSO) on renal glutathione concentration and aspartic acid transport has been studied by analyses of parts of individual freeze-dried glomeruli, early and late proximal convoluted, early and late proximal straight, and distal straight and convoluted tubules, and patches from thinlimb and papilla areas. Glutathione normally varies threefold along the kidney nephron, being highest in the convoluted and early straight proximal tubule, lowest in the distal straight tubule. Large loads of aspartate cause 20% diminution of glutathione in outer cortex, due entirely to changes in proximal tubule segments. MSO alone lowers glutathione 90% in all parts of the proximal tubule, with no change elsewhere. MSO does not affect the large increase in aspartate in proximal tubules caused by saturating aspartate loads, suggesting that glutathione is not directly involved in transport of this amino acid. Aspartate loads cause a large increase in renal glutamine, which is especially marked in the proximal straight tubule. MSO effectively blocks this increase and depresses tissue glutamine below normal levels.
A new approach to amino acid transport in kidney is described which may be useful for study of renal transport in general. The amino acid is given in threshold and above threshold loads along with inulin as a glomerular filtrate marker. The kidney is quickly frozen at --60 degrees. Frozen 16 mum sections are dried at --40 degrees, and identified parts of single nephrons are analyzed for amino acid given, certain metabolites and inulin. The relationship of amino acid to inulin along the tubule is used to indicate changes relative to the glomerular filtrate. With either aspartate or glutamate loads, both amino acids accumulate to high levels in segments in which transport is believed to take place (proximal convoluted and straight tubules). Glutamine also accumulates to a high degree, but only in the proximal straight tubule.
Renal transport was studied by direct analysis of specific segments of the nephron for the substance transported. Rats were given inulin plus loads of glutamate or aspartate. Glomeruli, six different identified segments, and patches from thin-limb and papillary areas were dissected from individual nephrons in freeze-dried sections. Large amounts of the amino acid (up to 35 mmol/kg) accumulated in segments in which transport is believed to occur. With subthreshold loads, large amino acid increments were confined to earlier proximal segments. With loads above threshold, increases occurred throughout the proximal tubule. The early convoluted tubule probably has less transport activity than the rest of the proximal tubule. Both dicarboxylic amino acids accumulate in large amount when one is given. Aspartate is probably formed within the tubule after a glutamate load. This new histochemical approach may have general applicability for more precise localization of transport cells, for assessing changes in those cells during transport, and for study of structures inaccessible to micropuncture.
The measurement of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity has been found to be a useful guide to lead exposure for screening purposes. The pH of the test should be well-controlled for adequate clinical interpretation. False-normal tests are rare even with iron-deficiency anemia or macrocytosis. Recent transfusion and recent bleeding or hemolysis with reticulocytosis tend to invalidate the test. ALA-D activity above 600 International Units effectively excludes significant lead exposure and eliminates the need for further testing. ALA-D activity is maximally depressed at a red cell lead concentration of 200 mug per 100 ml. When activity is moderately depressed, interpretation is difficult and the urinary excretion of lead after the administration of a chelating agent is usually required to differentiate the degree and significance of lead exposure.