Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
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Ten male rhesus monkeys, each weighing 3.5 kg, were divided into four groups of 3, 3, 2, and 2, and were fed daily with 100 g pelleted food containing 300, 30, 3, and 0 ppm cadmium, respectively. Urine samples were collected every 2 weeks and blood samples every 4 weeks. One monkey each of the 300 and 30 ppm groups was autopsied for pathological examination and tissue cadmium determination at the week 24 of the experiment; the remaining 8 animals were killed after 55 weeks. The lowest exposed group (3 ppm) did not show any specific biological response to cadmium over a period of 55 weeks. In the 30 ppm group, no significant changes were observed for up to 24 weeks, although cadmium concentration in the renal cortex and urine at 24 weeks were 300 mug/g wet weight and 18 mug/l., respectively. Plasma urea nitrogen and urine protein (quantitative determination) increased after 30 and 36 weeks. At 55 weeks of the experiment, qualitative tests were negative for low molecular weight proteinuria and glycosuria, and the results remained normal for renal and liver function tests and blood analysis, although cadmium concentrations in the renal cortex of two monkeys were 460 and 730 mug/g wet weight and those in the liver were 110 and 160 mug/g wet weight, respectively. In the highest exposure group (300 ppm), urine cadmium increased to 250 mug/l. by 11 weeks, and urine retinol-binding protein, plasma GOT, GPT, and LDH increased after 12 weeks. Proteinuria (quantitative determination), glycosuria, aminoaciduria (panaminoaciduria), and erythrocytopenia were observed after 16 weeks, when urine cadmium was 500-900 mug/l. Hypohemoglobinopathy and proteinuria (qualitative determination) were observed after 20 and 24 weeks, while cadmium concentrations in the renal cortex and the liver were 760 and 430 mug/g wet weight at 24 weeks, respectively. Slightly depressed tubular reabsorption of phosphate, increased urine beta(2)-microglobulin, increased plasma urea nitrogen, and increased plasma alpha(2)-globulin fraction (electrophoresis) were observed between 28 and 30 weeks of the experiment. Creatinine clearance and plasma cholinesterase decreased after 47 and 54 weeks, respectively. Cadmium concentrations in the renal cortex and the liver of two monkeys at 55 weeks were 350 and 580 mug/g wet weight and 410 and 630 mug/g wet weight, respectively. Pathological examinations revealed denaturation, destruction, and regeneration of the epithelial cells in renal proximal tubules, but no pathological changes in osseous tissues. Critical cadmium concentration in the renal cortex was estimated to be 380 mug/g wet weight for low molecular weight proteinuria and 470 mug/g wet weight for proteinuria, glycosuria, and aminoaciduria. Critical concentration in the liver was also estimated to be 210 mug/g wet weight. The apparent biological half-time of cadmium in monkeys at autopsied stage was calculated to be 0.66, 6.4, 5.2, and 22.4 years for the 300, 30, 3, and 0 ppm groups, respectively.
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PMID:Effects of dietary cadmium on rhesus monkeys. 11 86

During the initial 50 days following transplantation of a cadaver kidney into 8 patients, determinations of 7 individual protein clearances were performed twice a week. This, the first posttransplantation investigation of single protein clearances utilizing unconcentrated urine, was made possible by the highly sensitive electroimmunodiffusion method of LAURELL [24]. The following results were obtained: 1. Kidney implantation was immediately followed by glomerulo-tubular proteinuria. In patients exhibiting good transplant tolerance the tubular proteins disappeared from the urine by the 43rd day at the latest; on the other hand, excretion of the glomerular proteins transferrin and albumin continued. In patients without complications the proteinuria was already highly selective by the 7th day (70 degrees). 2. In 5 of 8 patients there was a change in the proteinuria pattern during the rejection crisis: glomerulo-tubular proteinuria occurred three times and glomerular proteinuria twice. In two of these cases there was a change in the selectivity. 3. Patients with good tolerance showed plasma prealbumin levels which increased as a function of the time lapse since transplantation. 4. The plasma concentration of retinol-binding protein did not vary following transplantation and remained at 16.8 +/- 2.8 mg% in patients with uneventful course and at 18.5 +/- 4.9 mg% in patients with transplant rejection reactions, both values being markedly above the norm (4.7 +/- 1.1 mg%, [1 SD]).
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PMID:[Proteinuria and kidney transplantation. A quantitative immunochemical study of 7 protein clearances during the first 50 days following implantation of cadaver kidney]. 33 96

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

Mental retardation in combination with proteinuria and a slight hyperlipoproteinemia was found in three brothers. The increased urinary protein excretion was dominated by albumin and the low molecular weight proteins retinol-binding protein (RBP) and beta2-microglobulin, indicating the presence of proximal tubular dysfunction. However, there was no glucosuria, phosphaturia or amino aciduria and the renal concentrating and acidification capacities were normal. A kidney biopsy in one of the patients revealed morphologic evidence of glomerular damage but a normal tubular structure. A mild hyper-beta-lipoproteinemia was found in the patients but not in their healthy siblings. The cause of this syndrome, hitherto not described, is unknown.
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PMID:Low molecular weight proteinuria and slight hyperlipoproteinemia in three mentally retarded brothers. 93 5

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified Zn-alpha2-glycoprotein (Zn-alpha2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39 +/- 7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn-alpha2 was measurable in the urine and was found to be 1.0 +/- 1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various renal diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol-binding protein (RBP, mol wt 21,000). A close correlation was found between the urine-to-plasma (U/P) ratios of Zn-alpha2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn-alpha2 and RBP were correlated. No significant renal arteriovenous difference in Zn-alpha2 could be demonstrated. The Zn-alpha2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn-alpha2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn-alpha2, substantially exceeding that of albumin, but notably lower than that of smaller low-molecular-weight proteins. An increased excretion of Zn-alpha2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.
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PMID:Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein. 98 27

To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), alpha 2 mu-globulin (alpha 2 mu) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was observed, together with transient increases in alpha 2 mu and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed alpha 2 mu accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with "glomerular" proteinuria, the alpha 2 mu cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary alpha 2 mu reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with alpha 2 mu for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of alpha 2 mu, caution should be exercised in extrapolating these findings to man.
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PMID:Rat model of perchloroethylene-induced renal dysfunctions. 128 47

Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.
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PMID:Low molecular weight proteins in children with renal disease. 128 25

The critical levels for monitoring cadmium health effects in 358 workers engaged in ore crushing/roasting (cadmium concentration in the workplace air 2.5-6.5 mg/m3), dry smelting (10.8-23.3 mg/m3), cadmium melting (0.01-0.16 mg/m3), and ingot making (2.8-4.7 mg/m3), were investigated. Exposure parameters such as blood and urinary cadmium were determined, together with biological parameters such as proteinuria, amino acids, glucose, beta 2-microglobulin, retinol-binding protein, albumin, plasma beta 2-microglobulin, creatinine clearance, tubular reabsorption of beta 2-microglobulin and phosphate, and blood and urinary levels of zinc, copper and lead. Factor analysis and stepwise regression analysis were then applied to the data to classify parameters and to find the main contributing parameter. Blood and urinary cadmium, urinary beta 2-microglobulin, retinol-binding protein and the ratio of urinary beta 2-microglobulin to albumin were also subjected to multiple correlation analysis, multiple regression analysis and the Chi-square test was applied to contingency tables. It is concluded, based on the data, that cadmium health effects may be assessed by using the following critical levels: blood cadmium: 10 micrograms/l, urinary cadmium: 10 micrograms/g creatinine; urinary beta 2-microglobulin: 2000 micrograms/g creatinine, urinary retinol-binding protein: 200 micrograms/g creatinine and a ratio of urinary beta 2-microglobulin to albumin of 0.001.
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PMID:Critical levels of blood and urinary cadmium, urinary beta 2-microglobulin and retinol-binding protein for monitoring cadmium health effects. 130 59

Statutory health surveillance of occupational exposure to cadmium exists in most Western countries. For biological monitoring, both indicators of internal dose and indicators of effect are available. Cadmium in urine is an indicator of chronic exposure and essentially reflects the body burden under low-exposure conditions and in the absence of renal damage. Whole blood cadmium is primarily a useful indicator for use in evaluations of recent exposures. Biological threshold limit values for cadmium in urine and blood are based on the correlation of biological levels with thresholds for renal dysfunction. The use of markers of high and low molecular weight proteinuria should be integrated into the health surveillance of cadmium-exposed workers. Priority should be given to the determination of albumin and of proteins such as beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin. Interpretation of biological monitoring data in terms of the threshold values requires a programme of periodic biological, medical and environmental monitoring.
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PMID:Biological monitoring in the occupational setting--relationship to cadmium exposure. 130 73

This study was designed to evaluate the occurrence and the type of proteinuria in 82 children with vesico-ureteric reflux (VUR) with or without renal scars. The urinary excretion of the high molecular weight protein albumin was taken as an index of glomerular alterations and the excretion of retinol-binding protein (RBP), beta 2-microglobulin and brush border antigens (BBA) (measured by monoclonal antibody-based enzyme-linked immunosorbent assay) was taken as an index of tubular alterations. All such markers were increased in children with VUR and were related to the degree of renal function. Patients showing reduced creatinine clearance had very high levels of albuminuria, microproteinuria and BBA, with all these variables reciprocally correlated. In children with normal renal function however, only microproteins (not albumin or BBA) were slightly increased, thus indicating an isolated tubular defect without involvement of the proximal segment of the tubule. However, microprotein excretion did not correlate with the grade of scarring (99mtechnetium-dimercaptosuccinic acid scan), both RBP and beta 2-microglobulin excretion being normal in 75% of children with radioisotopic signs of renal lesions but increased in 17% of children without scars. Therefore, tubular proteinuria identifies different groups of children with VUR but is not related to renal scarring. Prospective studies will define the usefulness of proteinuria as a reliable indicator of renal outcome.
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PMID:Urinary excretion of brush border antigens and other proteins in children with vesico-ureteric reflux. 131 Nov 86


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