Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In freshly collected urine from a patient with glomerulotubular proteinuria there were two bands which contained retinol-binding proteins. The cathodal band showed fluorescence in the ultraviolet. After extraction with organic solvents only the anodal non-fluorescent band remained. After addition of an excess retinol only one band remained which by mobility corresponded to the cathodal band. The anodal of the two bands was therefore probably the apo form and the cathodal the holo form of the same retinol-binding protein. Their proportions, determined by densitometric scanning were approximately 4/1 (anodal/cathodal band). More than 85% of the retinol-binding protein in the urine bound to prealbumin-Sephrose. The apo retinol-binding protein from urine had the same electrophoretic mobility on agarose gel el-ctrophoresis and the same pattern on isoelectric focusing as an retinol-binding protein prepared from serum. The carboxy-terminal amino acid sequence of the retinol-binding protein from freshly collected urine that bound to prealbumin-Sepharose, was -Arg-Leu. The amino-terminal sequence was Glu-Arg-Asp-Cys-Arg-Val-Ser-X-Phe-Arg-Val-Lys-Glu-Asn-Phe-Asp-Lys-Ala-Arg-Phe-X-Gly-Thr-Trp-Tyr-. This sequence and the amino acid composition are compatible with the view that the retinol-binding protein in urine is the same as in plasma.
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PMID:Retinol-binding protein from human urine and its interaction with retinol and prealbumin. 57 35

The light- and electron microscopic changes in the glomeruli of the rat's kidney have been investigated in the course of ageing and after subtotal nephrectomy, constriction of the renal vein, and intoxication by N-nitrosomorpholine. In spite of the fact that four different experimental models have been used, identical changes were always found in the glomeruli. Morphologically they consisted of a diffuse thickening of the glomerular basement membrane and of an increase in the mesangial matrix without a proliferation of the glomerular cells. Despite this thickening of the glomerular basement membrane, functionally an increased permeability of the glomerular capillaries for macroproteins could be observed, shown by a moderate proteinuria. For these morphological changes the term "glomerulosclerosis" is suggested; they are interpreted as a non-specific, non-inflammatory reaction of the glomerulus to an impairment caused by a number of varied influences. From the study of the formal pathogenesis of the glomerulosclerosis presented here one can conclude that in the individual experimental models the same result has been achieved in different ways. One possibility in the development of glomerulosclerosis is an increased production of the components of the basement membrane and of the mesangial matrix. This is the pathway which appears to be followed after nephrectomy. Another possibility is a slowing down of the breakdown of both the matrix and the membrane. This seems to be the case in the glomerulosclerosis occuring in the course of ageing, and after hypoxic and toxic changes. It could be accounted for by a functional disturbance of, presumably, the mesangial cells responsible for the breakdown of the basement membrane and of the matrix. On the other hand, one may have to consider a primary alteration of the macromolecules of these structures, as is already known from studies of the, chemically closely related, collagen. The light- and electron microscopic studies of the normal and of the altered glomeruli have led to certain conclusions concerning the origin and the fomation of the glomerular basement membrane and the mesangial matrix. In order to widen the scope of the studies, additional autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin and semithin sections of the rat's glomeruli. The results of the studies presented here suggest that of the three cell types of the glomerulus the visceral epithelial cells (podocytes, "Deckzellen") may participate on the formation of the glomerular basement membrane, whereas the mesangial cells appear to be responsible for the synthesis of the mesangial matrix.
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PMID:[On the pathogenesis of the glomerulosclerosis ultrastructural and autoradiographic investigations on the rat kidney (author's transl)]. 79 Aug 31

Intraperitoneal injection of bovine albumin in rats readily induces proteinuria. It is already known that this proteinuria is accompanied by ultrastructural and enzyme changes in the glomeruli. The purpose of the present study is to investigate whether these phenomena were associated with an increased glomerular protein synthesis or, more specifically, with an increased glomerular basement membrane (GBM) synthesis. Young rats were made proteinuric by the injection of bovine albumin. Their glomeruli were isolated by the sieve technique and incubater either with [U-14C]proline or with [U-14C]leucine and [U-14C]tyrosine. Control incubations were run with normal glomeruli. Glomerular proteins were hydrolyzed and analyzed for amino acid composition and radioactivity. Specific activities of all three amino acids were always higher in proteinuric glomeruli, but there was no difference in the ratio 14C-hydroxyproline/14C-proline. The similar increase in incorporation of the three amino acids must result from an increased synthesis of different cellular proteins and cannot be considered as a preferential increase in GBM synthesis.
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PMID:Glomerular protein synthesis in proteinuric rats. 83 65

The protein synthesizing capacity of liver parenchymal cells isolated from 3-, 12-, 24-, 31- and 36-month-old rats was determined by the incorporation of 14C-leucine. Conditions for optimum protein synthesis included the use of an enriched medium (modified Waymouth's MB 752/1) and cell suspension concentrations ranging from 0.25 to 4 X 10(6) cells/ml medium. The cells were incubated with a dose of 6 micronmol leucine/ml medium for 2 h at 37 degrees C under an atmosphere of 95% O2 and 5% CO2. With parenchymal cells isolated from 3-month-old rats, a leucine incorporation rate of 14.4 nmol leucine/h/10(6) cells was found. The capacity of the parenchymal cells to synthesize protein decreased between 3 and 12 months, remained constant between 12 and 24 months and increased between 24 and 26 months. Degradation of newly synthesized proteins or reutilization of 14C-leucine did not occur during the incubation period. The ratio between albumin and total protein synthesis as a function of age was determined. This ratio did not change between 3 and 24 months but there was a significant increase between 24 and 36 months. The increase in total protein synthesis in late age may be due to a compensation by the liver for a more pronounced proteinuria, increased proteolysis or an accumulation of "altered" proteins.
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PMID:The effect of age on protein synthesis by isolated liver parenchymal cells. 87 90

Two-color flow cytometry was carried out to determine the correlation between cell-mediated immunity and the levels of proteinuria in 30 patients with membranous nephropathy. Lymphocyte subpopulations were measured by two-color flow cytometry using various monoclonal antibodies of the Leu series. Clinically, the patients were divided into four stages as follows: 1. untreated nephrotic stage, 2. prednisolone (PSL) treated nephrotic stage, 3. persistent proteinuric stage (incomplete remission, ICR) and 4. complete remission (CR). Two-color flow cytometry showed a significant decrease in Leu 2a+15+ (suppressor T) cells and relative increase in Leu 3a+8+ (suppressor inducer T) cells in the untreated nephrotic stage. The mean Leu 3a+8-/Leu 2a+15+ (helper/suppressor) cell ratio was normalized in the persistent proteinuric stage or complete remission after treatment with PSL. Patients with membranous nephropathy showed a significant elevation of Leu 2a+DR+ cells after treatment with PSL. The abnormalities of suppressor T cells and suppressor inducer T cells in the peripheral blood appear to reflect the levels of proteinuria in patients with membranous nephropathy. It was concluded that PSL might stimulate Leu 2a positive cells and then increase the number of Leu 2a+15+ cells in the peripheral blood of patients with membranous nephropathy.
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PMID:Two-color analysis of lymphocyte subpopulations in patients with nephrotic syndrome due to membranous nephropathy. 151 83

Protein restriction ameliorates proteinuria in acute adriamycin (ADR) nephrosis and decreases the renal levels of xanthine oxidase (XO), a putative mediator of ADR nephrotoxicity. Hypothetically, the effect of protein restriction on renal XO levels may be due to variations in plasma and tissue proteic amino acids (AA). To elucidate this point, the levels of AA in plasma and in renal homogenates were determined in rats with ADR nephrosis and fed diets with different protein contents: (a) high (35%) casein; (b) standard (21%) casein; (c) low (9%) casein; (d) low casein plus a synthetic mixture of Val, Leu and Ile. The protein content of the diet determined certain marked variations in plasma AA: high levels of Val, Leu and Ile were found in rats fed on a high protein diet, while the same AA were low, in rats on low protein regimen. Supplementation of the low protein diet with a synthetic mixture of branched-chain AA (Val, Leu and Ile) normalized the plasma levels of these AA. In spite of these changes, tissue AA were similar in all groups, regardless of the protein contents of the diets. Furthermore, the levels of renal XO and proteinuria were unrelated to variations in plasma AA, since both parameters were low in protein-restricted and protein-restricted AA-supplemented rats while high in rats fed a high or normoproteic diet. These data demonstrate that low protein diets induce marked alterations in plasma AA composition which are similar in may respects to those found in protein malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of proteinuria and renal xanthine oxidase activity by dietary proteins in acute adriamycin nephrosis in rats: lack of correlation with intra- and extracellular amino acids. 156 88

Leukotriene B4 (LTB4) is the major 5-lipoxgenase product released during early experimental glomerulonephritis. To test its functional relevance, its actions in the normal rat kidney and its influence on renal function in the heterologous phase of mild nephrotoxic serum-induced glomerular injury were examined. Intrarenal administration of leukotriene B4 resulted in mild vasorelaxant and natriuretic responses which were shared by 12(R)-hydroxyeicosatetraenoic acid but not 12(S)-leukotriene B4 or 12(S)-hydroxyeicosatetraenoic acid, suggesting activation of a common recognition site with a requirement for 12(R) stereochemistry. The polymorphonuclear cell-specific activator, N-formyl-Met-Leu-Phe, stimulated leukotriene B4 production from isolated perfused kidneys harvested from nephrotoxic serum-treated rats to a significantly greater degree than from control animals treated with nonimmune rabbit serum. The renal production of leukotriene B4 correlated directly and strongly (r = 0.79, P less than 0.01) with renal myeloperoxidase activity, suggesting interdependence of leukotriene B4 generation and polymorphonuclear cell infiltration. In vivo, intrarenal administration of leukotriene B4 to rats with mild nephrotoxic serum-induced injury was associated with an increase in polymorphonuclear cell infiltration, reduction in renal plasma flow rate, and marked exacerbation of the fall in glomerular filtration rate, the latter correlating strongly with the number of infiltrating polymorphonuclear cells/glomerulus, whereas inhibition of 5-lipoxygenase led to preservation of glomerular filtration rate and abrogation of proteinuria. Thus, although devoid of vasoconstrictor actions in the normal kidney, increased intrarenal generation of leukotriene B4 during early nephrotoxic serum-induced glomerular injury amplifies leukocyte-dependent reductions in glomerular perfusion and filtration rates, likely due to enhancement of polymorphonuclear cell recruitment/activation.
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PMID:Functional significance of leukotriene B4 in normal and glomerulonephritic kidneys. 165 93

Heparan sulfate proteoglycan (HSPG) has been identified as an important determinant of glomerular permselectivity. We have previously reported that glomerular epithelial cells in culture synthesize HSPG, suggesting that in vivo these cells contribute to the HSPG present in the glomerular basement membrane. In this study we examined the effects of dexamethasone on the metabolism of HSPG core protein in cultured glomerular epithelial cells. Dexamethasone caused a dose-dependent and time-dependent increase in the HSPG core protein content of the cells. This effect was not seen with an equimolar concentration of aldosterone, indicating it was selective for dexamethasone. Dexamethasone caused a significant inhibition in 3H-leucine incorporation into de novo synthesized proteins at concentrations that caused maximum increment in the HSPG core protein content. These findings support the interpretation that HSPG core protein is a selective target for dexamethasone. Actinomycin-D completely abrogated the dexamethasone effect on HSPG core protein content, implying that enhanced transcription may be the major mechanism underlying the dexamethasone-induced increment in HSPG core protein content. Our findings suggest that glucocorticoids have important effects on the metabolism of the core protein moiety of heparan sulfate proteoglycan. Furthermore, these data imply that the glucocorticoid-induced amelioration of proteinuria could involve metabolic effects on the local determinants of glomerular permselectivity (e.g., HSPG) in addition to their well-known systemic anti-inflammatory effects.
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PMID:Dexamethasone increases heparan sulfate proteoglycan core protein content of glomerular epithelial cells. 213 58

Two-color flow cytometry was carried out to determine the correlation between cell mediated immunity and the development of the nephrotic stage in patients with membranous nephropathy (MN) and minimal change nephrotic syndrome (MCNS). In this study, lymphocyte subpopulations were measured by two-color flow cytometry using various monoclonal antibodies of the Leu series. Thirty patients with MN and 25 patients with MCNS were examined. Clinically, those patients were divided into four stages as follows: (1) untreated nephrotic stage, (2) prednisolone (PSL) treated nephrotic stage, (3) persistent proteinuria stage (incomplete remission, ICR), and (4) complete remission (CR). Pathologically, the patients with MN also divided into four stages I-IV, according to Churg's classification. The values of the Leu 3a/Leu 2a ratio in patients in the untreated nephrotic stage of MN and MCNS were significantly higher than those in the remission stage in both diseases (P less than 0.01, P less than 0.05, respectively). Two-color flow cytometry showed that the reduction of Leu2a positive cells was mainly due to a decrease of Leu 2a+15+ subsets (suppressor T cells) in the untreated nephrotic stage and relative increase of Leu 3a+8+ subsets (suppressor inducer T cells). There was no significant difference in these findings among the histopathological stages in patients with MN. Patients with MN and MCNS showed a significant elevation of Leu 2a+DR+ cells after the treatment of PSL. The abnormalities of suppressor T cells and suppressor inducer T cells in the peripheral blood appear to be correlated with clinical activities of the nephrotic syndrome due to MN or MCNS, but not to be related to the pathogenesis of either disease. It is postulated that PSL might stimulate Leu 2a positive cells and Leu 3a positive cells, and then increase the number of Leu 2a+15+ cells in the peripheral blood of patients with MN and MCNS.
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PMID:[Two-color analysis of lymphocyte subpopulations in membranous nephropathy and minimal change nephrotic syndrome]. 259 16

The nephrotoxic potential of alpha-interferon (IFN alpha-2b) was analysed in 21 patients with chronic myeloid leukemia. As particularly sensitive parameters in the detection of subclinical renal injury we measured the excretion of the following urinary enzymes: lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), leucine arylaminidase (LAP), beta-galactosidase (GAL) and N-acetyl-beta-glucosaminidase (NAG). Additionally, protein excretion and urinary sediment were analysed. In 18 of 21 patients a significant increase in the excretion of LDH, LAP, GGT and NAG was found, in 6 patients there was an additional rise in the output of GAL. Eleven patients developed proteinuria up to 2 g/l, one patient excreted up to 9 g/l. Enzymuria and protein excretion decreased in all patients after reduction of the IFN alpha-2b dosage and disappeared in two patients following cessation of therapy. The high incidence of nephrotoxic events in patients with CML during IFN alpha-2b therapy might be mostly due to immunological or substance-specific effects.
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PMID:[Detection of nephrotoxicity of human alpha 2b interferon with special reference to the analysis of urine enzymes in patients with chronic myeloid leukemia]. 347 5


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