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)

The effect of corticosteroids and cytotoxic chemotherapeutic agents on the excretion of Bence Jones protein was determined for periods of 1 - 62 mo in 29 patients with multiple myeloma and Bence Jones proteinuria. The amount of protein present in 24-h urine specimens collected before treatment and at frequent intervals during monthly treatment cycles was determined. Striking variations occurred in the amount of Bence Jones protein excretion; these changes were especially evident when 75 mg of prednisone were given daily for 7 days as part of a monthly chemotherapeutic regimen. Within the 7-day period seven patients showed essentially no decrease (<25%), whereas 13 and 9 patients had a moderate decrease (25-75%) or a marked decrease (>75%), respectively, in Bence Jones proteinuria as compared to pre-treatment values. The decrease in excretion of Bence Jones protein during this period was attributed mainly to corticosteroid therapy because of the transient nature of the response in most patients and the lack of such response in three patients when the hormone was omitted. Biosynthetic studies were performed to determine in vitro the effect of corticosteroids on Bence Jones protein synthesis. Plasma cells obtained from the bone marrow of 13 patients were incubated in a growth medium containing (14)C-labeled lysine and isoleucine and prednisone in concentrations up to 240 mug/ml, and the amount of Bence Jones protein synthesized was determined immunochemically. No differences in viability were apparent between untreated and prednisone-treated cells. The type of response exhibited by an individual patient in the percent decrease of Bence Jones protein excreted after 7 days of prednisone treatment was comparable to the percent decrease in newly-synthesized Bence Jones protein secreted by tumor cells when cultured in the presence of prednisone at a concentration of 120 mug/ml. The marked differences in the capacity of corticosteroids to affect Bence Jones protein synthesis appear to reflect a biochemical heterogeneity among plasma cell neoplasms.
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PMID:Bence Jones proteins and light chains of immunoglobulins. XV. Effect of corticosteroids on synthesis and excretion of Bence Jones protein. 61 16

The effects of indomethacin and lysine acetylsalicylate (L-ASA) were compared in rats in which autologous nephrotoxic serum nephritis had been induced. The aim of this study was to offer support to the hypothesis that indomethacin might reduce proteinuria through increased synthesis of glomerular basement membrane by the podocytes. Both drugs were injected intraperitoneally at the dosage of 4 mg/kg body weight daily during a 6-day period into 40 rats rendered nephritic by rabbit nephrotoxic serum injection. Rats treated with indomethacin showed a marked decrease of proteinuria (tested by the 3% sulfosalicylic aicd method) and a clear ultrastructural picture of hyperplasia and hypertrophy of podocytes. Rats given L-ASA showed only a slight correction of proteinuria and less specific ultrastructural modification. These observations suggest that indomethacin decreases proteinuria in nephritic rats not only through its anti-inflammatory activity, but possible also by a peculiar mechanism, namely an increase in podocytic basement membrane synthesis.
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PMID:Indomethacin and lysine acetylsalicylate in rats with autologous nephrotoxic serum nephritis. Biochemical and morphological studies. 74 Jan 8

1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for the renal tubular turnover of small filtered proteins in man. Lysine potently inhibits tubular peptide uptake, and may thus depress the uptake and metabolism of aprotinin. This was investigated in 14 glomerulonephritic patients with normal renal function and variable proteinuria and in one healthy subject. 2. 99mTc-labelled aprotinin was given intravenously alone, and again 3 days later, immediately after the intravenous administration of 3-6 g of lysine, followed by an infusion over 1 h of 0.3-1.9 g of lysine/kg in individual patients. Activity over kidneys and in urine was measured over 24 h and chromatography was used to separate the undegraded peptide from free isotope. 3. At the low dosage of lysine (< 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake) was unchanged, but early urine samples contained some undegraded aprotinin. Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6 +/- 0.2% of dose/h with no lysine to 0.9 +/- 0.1% of dose/h in the 24 h after lysine, suggesting suppression of tubular aprotinin degradation. Corrected fractional degradation was calculated from the mean urinary excretion of free isotope over a given interval, determined by chromatography, divided by the mean cumulative kidney counts over this same interval, and this also fell after lysine from 0.06 +/- 0.006 to 0.03 +/- 0.006 h-1 (P < 0.005) between 3.75 and 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in man. 138 15

Glomerulopathy and nephrotic syndrome were induced in rats by intravenous puromycin aminonucleoside. Ten days after the injection of puromycin, the animals have developed heavy proteinuria. During this phase, glomerular epithelial cell endocytosis was studied by injecting a conjugate of horseradish peroxidase and poly-L-lysine. This conjugate has been shown to be endocytosed by glomerular epithelial cells. The rats were serially sacrificed from 1 min to 24 h after this injection. Peroxidase was localised cytochemically and observed at light and electron microscopy. The early events of endocytosis in glomerulopathy (namely the binding to the plasma membrane, the membrane invagination and the formation of the early vesicles) were qualitatively similar to those in the normal. The later events (the fusion of the vesicles and their movement within the cells) were inhibited. The results show that puromycin aminonucleoside damages epithelial cell endocytotic activity and affects the later processing of the conjugate within the cells.
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PMID:Glomerular epithelial cell endocytosis in puromycin-induced glomerulopathy. 143 98

Cross-linking glomerular basement membrane (GBM) has been shown to render it more permeable to protein. Isolated pig GBM was cross-linked with dimethylmalonimidate which reacts selectively with lysine epsilon-NH2 groups or with glutaraldehyde, a less selective cross-linking agent. Studies of the ultrafiltration properties of these materials in vitro using cytochrome c, myoglobin, bovine serum albumin and immunoglobulin showed that cross-linking had markedly increased solvent and protein fluxes as compared with native membranes particularly at higher pressures. Filtration studies with serum demonstrated that the cross-linked membranes were more permeable to serum proteins. Thickness measurements under pressure indicated that cross-linked membrane was less compressed than native membrane as pressure was increased. Pore theory did not provide a suitable model for analysis of the results, but analysis of the results using the fibre-matrix hypothesis indicated that cross-linking had the effect of bundling together the fibres (type IV collagen) in the GBM matrix. The effect of cross-linking on filtration could be explained by a combination of contraction of the membrane, fibre bundling and increased rigidity compared with native membrane. Cross-linking of GBM might lead to long-term damage of the glomerular capillary wall in nephritis, so promoting proteinuria.
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PMID:Studies of the permeation properties of glomerular basement membrane: cross-linking renders glomerular basement membrane permeable to protein. 154 78

1. In minimal change nephrotic syndrome the occurrence of heavy proteinuria can be explained on the basis of a reduction in charge selectivity of the glomerular filtration barrier, and it has been proposed that this might be caused by the neutralization of anionic groups by a circulating polycationic factor. 2. The effects of two polycations, protamine and poly-L-lysine, on the function of the isolated perfused rat kidney have been examined. 3. Poly-L-lysine polymers of relatively high molecular weight (8800 and 17,800) induced heavy proteinuria, while simultaneously causing a marked increase in renal vascular resistance and a fall in filtration rate. Protamine (approximate molecular weight 7000) at relatively high concentration induced modest proteinuria in the absence of effects on vascular resistance or filtration rate. 4. A poly-L-lysine polymer of lower molecular weight (3800) did not induce proteinuria. Protamine at a concentration of 40 micrograms/ml and below did not affect protein excretion either. Both provoked substantial natriuresis. This appeared to be largely due to an effect on the tubular handling of sodium since the filtration rate remained steady while fractional sodium excretion rose markedly. 5. The natriuretic effect of protamine was blocked by heparin, but not by indomethacin or verapamil, suggesting that the mechanism of natriuresis did not depend upon either prostaglandin production or entry of calcium through verapamil-sensitive channels.
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PMID:Effect of polycations on the function of the isolated perfused rat kidney. 217 45

Effects of cadmium intoxication on renal transport systems for various amino acids were studied. Subcutaneous injections of CdCl2, at a dose of 2 mg Cd/kg.day for 2 weeks, resulted in polyuria, proteinuria, glycosuria, phosphaturia, and aminoaciduria, as observed in chronic cadmium-intoxicated humans and experimental animals. The nature of aminoaciduria was nonspecific, including iminoacid as well as almost all species of neutral, acidic, and basic amino acids. In renal cortical brush border membrane vesicles isolated from cadmium-intoxicated rats, Na(+)-dependent transport of L-proline, L-alanine, and L-lysine was markedly attenuated, whereas the amino acid transport in the basolateral membrane vesicle was not significantly affected. Similar results were obtained in the normal membrane vesicles directly exposed to inorganic cadmium. These results indicate that cadmium intoxication impairs various Na(+)-amino acid cotransport systems in the renal brush border membrane, which leads to panaminoaciduria.
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PMID:Alteration of renal amino acid transport system in cadmium-intoxicated rats. 225 75

The glomerular polyanion comprises all anionic sites of glomerular cell surfaces, basement membranes and extracellular matrix. Charged structures may play a critical pathophysiologic role within the glomerular microcirculation, as loss of charges results in altered permselectivity of the filtration barrier and proteinuria. Neutralization of cell surface negative charges of cultured glomerular epithelial and mesangial cells by the polycation poly-L-lysine (PL) is accompanied by increased prostanoid synthesis. Recent studies have shown that PL enhances mesangial cell proliferation in culture. Conversely, the polyanion heparin prevents the effect of PL, and inhibits the growth-stimulatory effect of serum. Thus, our data suggest that the glomerular polyanion, in addition to maintaining the integrity of the filtration barrier, regulates key cell functions such as eicosanoid biosynthesis and proliferation.
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PMID:Glomerular polyanion and control of cell function. 225 71

Rats were treated with a single intravenous injection of aminonucleoside of puromycin and were sacrificed between 1 and 21 days after injection. The conjugate of horseradish peroxidase with a poly-L-lysine (HRP.PL) was used to reveal endocytotic activity in glomerular epithelial cells (GEC). This conjugate was injected intravenously 2 h before each sacrifice. Renal tissue was taken and treated cytochemically with a conventional DAB technique and observed by light and electron microscopy. The assessment of endocytosis by glomerular epithelial cells was performed on 1-micron sections by counting HRP.PL grains in the GEC and expressing this in terms of the area of glomerulus examined. The results were compared to those found in normal rats. Our results show that GEC endocytotic function was reduced during the whole period of the experiment. It fell quickly from 1 day after puromycin injection and reached the most marked reduction on the 4th day, preceding the peak of proteinuria which was between 7 and 12 days. From the 5th day onward the endocytotic function gradually recovered, but was still abnormal at the end of the experiment.
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PMID:Endocytosis of cationized horseradish peroxidase by glomerular epithelial cells is reduced in puromycin glomerulopathy. 227 26

Urinary protein excretion was measured before and after the intravenous infusion of lysine in 14 normal subjects after 4-6 days' acclimatization at 4846 m. Urinary albumin excretion before lysine was elevated in 11 subjects but alpha 1-microglobulin was detected in only four. After lysine a large increase in albumin excretion occurred in all subjects. Together with the absence of alpha 1-microglobulin before lysine this implies that increased glomerular capillary permeability is the major cause of proteinuria after acclimatization to high altitude. The estimated minimum glomerular fluid albumin concentration was increased two to three fold above the published values in normal controls.
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PMID:The origin of proteinuria at high altitude. 244 62


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