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)

Heymann nephritis developed in rats immunized with brush border membrane fractions isolated from rat kidney tubules. Glomerular autoantibodies eluted from cryostat sections of nephritic kidneys reacted in immunoelectron microscopy with the outer surface of isolated brush border membrane vesicles. This indicates that the autoantigens are plasma membrane components. To characterize further the chemical nature of the nephritogenic autoantigens, we treated the brush border membranes with trypsin and sodium deoxycholate, and the solubilized membranes were then fractionated by lectin affinity chromatography. The polypeptide composition of the fractions was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The capacity of the membrane fractions to induce Heymann nephritis was assessed by observing the development of typical renal lesions, antibrush border autoantibodies, and proteinuria in rats immunized with these fractions. The results suggest that the nephritogenic autoantigen is an integral component of the brush border membrane of kidney proximal tubules and has an affinity for Lens culinaris agglutinin. This indicates that it is a glycoprotein and has mannosyl and/or glycosyl groups exposed in its oligosaccharide side chains.
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PMID:Heymann nephritis induced by kidney brush border glycoproteins. 744 31

Autoantibodies from many patients with systemic lupus erythematosus bind the Sm autoantigen B/B' polypeptide. The binding of serial serum specimens to the 233 overlapping octapeptides of Sm B/B' have shown that of the B/B'-derived octapeptides, PPPGMRPP and PPPGIRGP are early targets of the autoimmune response in some lupus patients. Rabbits immunized with PPPGMRPP and PPPGIRGP develop antibodies which not only bind these octapeptides, but also subsequently bind many other octapeptides of Sm B/B'. Eventually, the rabbits immunized with one octapeptide develop autoantibodies that bind other spliceosomal proteins including D, 70K, A, and C. Any mechanisms that operate to maintain tolerance or anergy for the spliceosome are thus overcome. Features considered typical of human systemic lupus erythematosus are also found in these peptide-immunized animals, such as antinuclear antibodies, anti-Sm precipitins, anti-double-stranded DNA, thrombocytopenia, seizures, and proteinuria. This disease model provides access to a mechanism for the development of humoral autoimmunity and may provide a basis to explain the immunopathogenesis of lupus in humans.
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PMID:Immunoglobulin epitope spreading and autoimmune disease after peptide immunization: Sm B/B'-derived PPPGMRPP and PPPGIRGP induce spliceosome autoimmunity. 753 Jul 56

Lecithin:cholesterol acyltransferase (LCAT) deficiency is a genetic disorder associated with low levels of serum HDL cholesterol. The proband of the Finnish LCAT-deficient family had corneal opacities, proteinuria, anemia with stomatocytosis, low serum HDL cholesterol (0.27 mmol/L), and low LCAT activity. Sequence analysis of his LCAT gene revealed compound heterozygosity for two different mutations: a C insertion in exon 1 between nucleotides 932 and 937 and a C-to-T point mutation in exon 6 at position 4976. The C insertion in exon 1 is predicted to result in premature termination and a truncated polypeptide containing only 16 amino acids. The C-to-T point mutation in exon 6 substitutes cysteine for arginine at residue 399. The functional significance of the Arg399-->Cys mutation was examined by expressing the mutated and wild-type LCAT cDNAs in COS cells. COS cells transfected with mutated and wild-type cDNAs showed comparable levels of mature LCAT mRNA. However, LCAT activity in the cell media of COS cells transfected with the mutant LCAT cDNA was significantly lower than that of COS cells transfected with the wild-type cDNA (1.4% versus 12.0% cholesterol esterified, respectively). A polymerase chain reaction-based duplex assay, in which both mutations can be detected simultaneously, was used for preliminary screening of Finnish subjects with serum HDL levels below 0.9 mmol/L; two additional individuals heterozygous for the Arg399-->Cys mutation were identified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two different allelic mutations in a Finnish family with lecithin:cholesterol acyltransferase deficiency. 774 57

Primary or AL amyloidosis occurs in patients with monoclonal plasma cell-related disorders and is typically associated with the systemic deposition as amyloid fibrils of the light-chain portion of the immunoglobulin molecule. Recently, the discovery that heavy chains could be involved in amyloid formation led to the designation of this type of disease process as AH amyloidosis. We have now identified a second example of heavy chain-associated amyloidosis in a patient (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. In this case, the renal and splenic amyloid deposits consisted solely of the VH-D-encoded portion of the heavy polypeptide chain, in contrast to the first case, where the amyloid contained an immunoglobulin component composed of the entire heavy-chain variable and third constant domains. In this respect, the chemical composition of the amyloid protein MAD differed not only from that of the first reported case of AH amyloidosis but from all other structurally abnormal components found in patients with heavy chain-associated disease. The discovery that certain forms of heavy chains, as well as light chains, can form amyloid provides further information on the chemical basis of amyloidogenicity and the diverse nature of this disease.
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PMID:Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis). 814 Nov 23

Cadmium is widely used in industry, causing exposure of workers and environmental pollution because of its persistence in the biosystems. Its very long half-life in the human organism causes its accumulation over the lifetime in liver and kidneys. Cadmium ions have a high affinity for tissue thiols, induce the synthesis of a carrier cysteine-rich polypeptide called metallothionein, and impair proteoglycan metabolism. Significant renal effects include tubular nephropathy manifested by proteinuria, amino aciduria, glucosuria, phosphaturia, and calcium wastage. Chronic sequels include decrease in the glomerular filtration rate and increased risk of kidney stone disease. Biological monitoring of cadmium absorption includes determination of urinary cadmium and of low molecular weight marker proteins, such as beta2-microglobulin or retinol binding protein, the tubular reabsorption of which is impaired before a frank proteinuria.
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PMID:Cadmium-associated renal disease. 857 Aug 61

Beta2-Microglobulin (beta2-m) is a polypeptide that is freely filtered and then mostly reabsorbed and degraded in the proximal renal tubule. Beta2-m is a marker of glomerular filtration (GFR) in renal failure, whereas urinary beta2-m is a marker of proximal renal tubular dysfunction. Preeclampsia (PE) (ie, de novo hypertension in pregnancy with accompanying renal, cerebral, or liver disease or thrombocytopenia) often has renal involvement characterized by proteinuria, decreasing glomerular filtration, or renal tubular dysfunction. The aim of this study was to determine whether serum beta2-m concentration or urinary beta2-m excretion were greater in women with PE than in women with gestational hypertension (GH) (ie, isolated de novo hypertension in the second half of pregnancy) and normal pregnant women. Seventy-five pregnant women (35 with PE, 22 with GH, and 18 normotensives) were studied prospectively. Serum creatinine and beta2-m concentrations, 24-hour proteinuria, and fractional excretion (FE) of beta2-m were measured. Preeclamptics had similar serum creatinine but higher serum beta2-m (3.26+/-0.99 mg/L) than gestational hypertensives (2.44+/-0.77 mg/L; P = 0.016), and both groups had higher serum beta2-m than controls (1.62+/-0.54 mg/L; P = 0.001). FE of beta2-m was similar amongst groups (PE: 0.27%; interquartile range [IQR]: 0.20-0.86; GH: 0.21%; IQR: 0.11-0.40; controls: 0.26%, IQR: 0.12-0.69). PE is characterized by higher serum beta2-m but similar serum creatinine to GH. Because FE beta2-m is similar in these groups, this implies reduced filtering of beta2-m in PE rather than altered tubular handling of beta2-m. Further studies are now necessary to assess whether measurement of serum beta2-m is helpful in the clinical management of the hypertensive disorders of pregnancy.
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PMID:Beta2-microglobulin in hypertensive pregnancies. 946 2

Diabetic nephropathy (DN) is characterized structurally by progressive mesangial deposition of extracellular matrix (ECM). Transforming growth factor-ss (TGF-ss) is considered to be one of the major cytokines involved in the regulation of ECM synthesis and degradation. Several studies suggest that an increase in urinary TGF-ss levels may reflect an enhanced production of this polypeptide by the kidney cells. We evaluated TGF-ss in occasional urine samples from 14 normal individuals and 23 patients with type 2 diabetes (13 with persistent proteinuria >500 mg/24 h, DN, 6 with microalbuminuria, DMMA, and 4 with normal urinary albumin excretion, DMN) by enzyme immunoassay. An increase in the rate of urinary TGF-ss excretion (pg/mg U Creat.) was observed in patients with DN (296.07 +/- 330.77) (P<0.001) compared to normal individuals (17.04 +/- 18.56) (Kruskal-Wallis nonparametric analysis of variance); however, this increase was not observed in patients with DMMA (25.13 +/- 11.30) or in DMN (18.16 +/- 11.82). There was a positive correlation between the rate of urinary TGF-ss excretion and proteinuria (r = 0.70, alpha = 0.05) (Pearson's analysis), one of the parameters of disease progression.
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PMID:Transforming growth factor beta activity in urine of patients with type 2 diabetes and diabetic nephropathy. 1058 34

The clinical significance of the BJ-protein is quite variable: from an asymptomatic course of the light chain proteinuria for a long period of time to specific tissue deposits with serious organ damages and dysfunction. On the basis of literature data a classification of the light chain diseases is proposed: 1. Essential (bening) BJ-proteinuria; 2. Smoldering BJ-myeloma; 3. Light chain disease--BJ myeloma; 4. Light (and heavy) chain deposition disease: LC granular thick deposits mostly k type on electron microscopy, belonging to the constant region of the polypeptide chain and actively reacting with antiserums, not possessing tincturial properties; 5. LC cast nephropathy--LC coprecipitates in the tubular system; 6. LC crystaline deposition disease--specific crystaloid structures (in the Fanconi syndrome and experimental nephropathies); 7. AL-amyloidosis: LC precursor mostly lambda type from the variable region with specific fibrilar structure and typical tincturial properties. The suggested classification would resolve the diagnostic difficulties and determine the correct therapeutic management.
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PMID:[Light chain diseases--pathogenetic forms, diagnostic criteria. A suggestion for classification]. 1122 63

Edema, proteinuria, hypertension (EPH-gestosis), most commonly termed as pre-eclampsia, is the most common pregnancy-associated pathological syndrome. It is accompanied by a thorough remodelling of extracellular matrix in the umbilical cord tissues. It is commonly known that the presence of serum in culture medium strongly stimulates many functions of cells cultured in vitro. It was decided to check how the pre-eclamptic serum affects the fibroblast division in culture. Ki-67 is a protein present in proliferating cells and can be detected during all phases of the cell cycle (G1, S, G2/M) but not in resting (G0) cells. PCNA (proliferating cell nuclear antigen) is an intranuclear polypeptide whose synthesis rate is at its maximum during the S-phase of the cell cycle. The expression of Ki-67 and PCNA was measured by immunocytochemical methods and biosynthesis of DNA was evaluated by [14C]-thymidine incorporation. The activity of pre-eclamptic umbilical cord serum (UC-serum) was found to be distinctly lower in comparison to control one. The expression of Ki and PCNA in fibroblast cultures treated with pre-eclamptic serum was also distinctly lower. Also the incorporation of [14C]-thymidine to DNA was lower than in the cultures treated with control UC-serum. It may by concluded that pre-eclampsia reduces the mitogenic activity of the umbilical cord serum.
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PMID:The effect of pre-eclamptic umbilical cord serum on fibroblast division in culture. 1250 91

This study investigates proteomic analysis of urinary samples as a non-invasive method to detect acute rejection of renal allografts. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was used to analyze urinary samples in 19 patients with different grades of subclinical or clinical acute rejection (BANFF Ia to IIb), 10 patients with urinary tract infection and 29 patients without evidence of rejection or infection. A distinct urinary polypeptide pattern identified 16 out of 17 cases of acute tubolointerstitial rejection, but was absent in two cases of vascular rejection. Urinary tract infection resulted in a different polypeptide pattern that allowed to differentiate between infection and acute rejection in all cases. Potentially confounding variables such as acute tubular lesions, tubular atrophy, tubulointerstitial fibrosis, calcineurin inhibitor toxicity, proteinuria, hematuria, allograft function and different immunosuppressive regimens did not interfere with test results. Blinded analysis of samples with and without rejection showed correct diagnosis by CE-MS in the majority of cases. Detection of acute rejection by CE-MS offers a promising non-invasive tool for the surveillance of renal allograft recipients. Further investigation is needed to establish polypeptide patterns in vascular rejection and to explore whether changes in the urinary proteome occur before the onset of histologically discernible rejection.
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PMID:Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients. 1616 98


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