Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sputum samples from 25 patients with bronchiectasis were assayed enzymatically for myeloperoxidase, neutrophil elastase and cathepsin B, and immunologically for cystatin A, cystatin B, cystatin C, cystatin S and kininogen. High myeloperoxidase and neutrophil elastase levels were found in those sputum samples that were assessed visually to be purulent. These samples were also found to contain high levels of cathepsin B activity and cystatin A, but low levels of cystatin S and of the most effective cathepsin B inhibitor, cystatin C. In contrast, sputum samples that were low in myeloperoxidase and neutrophil elastase activities had low levels of cathepsin B and cystatin A, but high cystatin C and S levels. It is concluded that cathepsin B activity in sputum is positively correlated with the degree of inflammation and neutrophil recruitment. Although this may be due in part to reduced amounts of cathepsin B inhibitors, particularly cystatin C, theoretical considerations suggest that factors other than the gross level of inhibitors must be involved in the control of cathepsin B activity.
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PMID:Levels of neutrophil elastase and cathepsin B activities, and cystatins in human sputum: relationship to inflammation. 223 63

The regional distribution and cellular localization of cystatin C in neurons of human postmortem hypothalamic was studied by use of peroxidase-anti-peroxidase technique. Cystatin C (earlier named gamma-trace) was found to be present in multiple nerve cells belonging to nuclei supraopticus, paraventricularis and arcuatus. We speculate that the occurrence of cystatin C in human cerebrospinal fluid is the result of a release of the protein from these neurons into the ventricular system.
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PMID:Cystatin C containing neurons in human postmortem hypothalamus. 338 Mar 52

gamma-Trace was demonstrated by the immunohistochemical peroxidase/anti-peroxidase technique to occur in normal chromaffin cells of the adrenal medulla from African green monkey, capuchin monkey and beagle dog and in the cells of a norepinephrine-producing human phaeochromocytoma. The presence of gamma-trace in the endocrine epithelial cells of the adrenal medulla suggests that gamma-trace might be related to the neuroendocrine system.
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PMID:Demonstration of gamma-trace in normal endocrine cells of the adrenal medulla and in phaeochromocytoma. An immunohistochemical study in monkey, dog and man. 675 Oct 8

We developed a sandwich enzyme immunoassay for determining cystatin C in serum by using commercially available antibodies. We optimized each assay step (e.g., concentrations of coating rabbit anti-human cystatin C antibodies and horseradish peroxidase-conjugated antibodies) and studied the binding kinetics of antigen and antibodies. The within-assay CV was < 5%, the between-assay CV was 8.8%, the detection limit was 0.9 microgram/L, and the assay can be performed within 2 h. Cystatin C concentrations in sera from men were significantly higher than in women (mean and SD: 2.14 +/- 0.31 vs 1.78 +/- 0.26 mg/L). We studied the cystatin C concentrations in sera of 31 outpatients with suspected kidney damages to characterize the behavior of this low-M(r) protein as a possible indicator for estimating the glomerular filtration rate. The correlation with the values obtained by a standard isotopic method involving 99mTc-diethylenetriaminopentaacetic acid was rs = -0.89. The diagnostic sensitivity of cystatin C was 88.2% of that of the standard isotope clearance method and better than those of the conventional serum indicators of reduced kidney function, beta 2-microglobulin (64.7%) and creatinine (52.9%).
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PMID:Sandwich enzyme immunoassay of cystatin C in serum with commercially available antibodies. 837 65

Biotin-labelled peptidyl diazomethane inhibitors of cysteine proteinases, based on the N-terminal substrate-like segment of human cystatin C, a natural inhibitor of cysteine proteinases, were synthesized. These synthetic derivatives were tested as irreversible inhibitors of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, to compare the kinetics of the inhibition of the parasite proteinase with that of the mammalian cathepsins B and L. The accessibility of the active sites of these proteinases to these probes was also investigated. The inhibition of cruzipain by Biot-LVG-CHN2 (where Biot represents biotinyl and L,V and G are single-letter amino acid residue abbreviations) and Biot-Ahx-LVG-CHN2 (where Ahx represents 6-aminohexanoic acid) was similar to that of unlabelled inhibitor. Biotin labelling of the inhibitor slowed the inhibition of both cathepsin B and cathepsin L. Adding a spacer arm (Ahx) between the biotin and the peptide moiety of the derivative increased the inhibition of cathepsin B but not that of cathepsin L. The discrimination provided by this spacer is probably due to differences in the topologies of the binding sites of proteinases, a feature that can be exploited to improve targeting of individual cysteine proteinases. Analysis of the blotted proteinases revealed marked differences in the accessibility of extravidin-peroxidase conjugate to the proteinase-bound biotinylated inhibitor. Cruzipain molecules exposed to Biot-LVG-CHN2 or Biot-Ahx-LVG-CHN2 were readily identified, but the reaction was much stronger when the enzyme was treated with the spacer-containing inhibitor. In contrast with the parasite enzyme, rat cathepsin B and cathepsin L treated with either Biot-LVG-CHN2 or Biot-Ahx-LVG-CHN2 produced no detectable bands. Papain, the archetype of this family of proteinases, was poorly labelled with Biot-LVG-CHN2, but strong staining was obtained with Biot-Ahx-LVG-CHN2. These findings suggest that optimized biotinylated diazomethanes might considerably improve their selectivity for the T. cruzi target enzyme.
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PMID:Biotin-labelled peptidyl diazomethane inhibitors derived from the substrate-like sequence of cystatin: targeting of the active site of cruzipain, the major cysteine proteinase of Trypanosoma cruzi. 880 25

The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
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PMID:Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes. 1058 30

Cystatin C is the best known extracellular endogenous cysteine proteinase inhibitor and has been studied as a possible index of tumor growth and as a marker of the effectiveness of antitumor therapy. The aim of this study was to evaluate cystatin C concentrations in murine tumor tissues (compared with other organs not directly involved with tumor development, such as the liver and spleen) during treatment with several antitumor drugs (Ukrain and/or cyclophosphane). Cystatin C concentrations in murine tissues and biological fluids was determined by enzyme-linked immunosorbent (ELISA) assay. The cystatin C ELISA test is a sandwich immunoassay, which uses immobilized rabbit antihuman cystatin C Pab and mouse antihuman cystatin C Mab-HRP (monoclonal antibodies, conjugated with horseradish peroxidase). We observed decreased serum cystatin C concentrations compared with controls in all nontreated tumor models: HA-1 hepatoma (solid and ascitic forms), lung adenocarcinoma (solid and ascitic forms) and LS lymphosarcoma. In the ascitic fluid of mice with HA-1 hepatoma the cystatin C concentration was much lower than in the serum of the same mice (about 20-fold lower). In the HA-1 model of hepatoma cells cystatin C concentration decreased about 2-3-fold compared with the control (intact liver) and Ukrain significantly increased the cystatin C concentration. Cyclophosphane treatment of LS lymphosarcoma significantly increased the cystatin C concentration in serum. Cyclophosphane treatment (50 mg/kg, single injection) increased cystatin C by up to 8-fold more in tumor issue. Ukrain treatment of LS lymphosarcoma was also followed by increased levels of cystatin C in tumor tissue (4-fold); cyclophosphane plus Ukrain had a similar positive effect. In the group with LS lymphosarcoma Ukrain or cyclophosphane plus Ukrain treatment induced a significant increase in cystatin C concentration in liver. Liver cystatin C concentration decreased in the HA-1 hepatoma group and treatment with Ukrain or carboxymethylated beta-1, 3-glucan (CMG) increased this index in both groups. Spleen cystatin C concentrations decreased about 5-fold in LS lymphosarcoma compared with controls and combined treatment with cyclophosphane plus Ukrain restored the index to the normal value. We can conclude that both murine tumors studied were characterized by low cystatin C concentrations in tumor tissues and decreased cystatin C concentrations (to a lesser degree) were also observed in liver and spleen as a result of the "toxic" effect of tumor bearing. Effective treatment in all cases (especially with Ukrain or a combination of cyclophosphane plus Ukrain) induced a significant increase in cystatin C. Obviously, the decrease in cystatin C concentration predominantly in tumor tissue was connected with tumor development and restoration of cystatin C level may be used as a marker of efficacy of antitumor therapy.
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PMID:Cysteine proteinase inhibitor level in tumor and normal tissues in control and cured mice. 1134 42

A sandwich-type ELISA has been developed for quantification of the complex between the cysteine proteinase cathepsin B (CB) and its reversible tight-binding inhibitor cystatin C (CC) in normal and pathological sera. The assay is based on a combination of catching Ab (3E1), raised against CB, and a horseradish peroxidase-labelled detection Ab (1A2), raised against CC. Only the CB/CC complex is able to evoke a signal in this assay. The detection limit of the assay was 15.5 nM and the working range between 31.3-200 nM. The within and between-run coefficients of variance (CV) varied from 4.7% to 9.4% and 11% to 12.8%, respectively, demonstrating satisfactory reproducibility of the method. The concentration of the CB/CC complex was determined in sera from 90 healthy controls, 32 patients with non-cancerous lung diseases, 148 patients with lung and 32 patients with colorectal cancer. The CB/CC complex was significantly less abundant in sera of patients bearing malignant lung tumours than in those with non-cancerous lung diseases or healthy controls (p<0.001). In colorectal cancer sera its level was significantly lower in advanced stages C and D than in early Dukes' stages A and B (p=0.02). Our results show that the increased levels of CB in malignant sera are not impaired effectively by CC and support the hypothesis of hindered inhibitory capability during cancer progression.
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PMID:Cathepsin B/cystatin C complex levels in sera from patients with lung and colorectal cancer. 1151 34

In systemic small vessel vasculitides, patients form autoantibodies against neutrophil granular proteins, anti-neutrophilic cytoplasmic autoantibodies (ANCA). Some correlation is seen between ANCA titre and disease activity, but whether this is cause or effect is still unknown. It has been reported that levels of proteinase 3 (PR3), one of the main ANCA antigens, are increased in patients with active disease. An increased level of circulating antigen could mean a predisposition to autoimmunity. In order to explore this we measured PR3 levels in patients with stable disease. In addition we measured neutrophil gelatinase-associated lipocalin (NGAL) as a specific marker of neutrophil degranulation, cystatin C as a marker of renal function as well as C-reactive protein (CRP), IL-6 and sTNFr1 as markers of inflammation. PR3, NGAL, IL-6 and sTNFr1 were measured in plasma by the ELISA technique. In the PR3 ELISA, we used anti-PR3 monoclonal antibodies as capture-antibodies and affinity-purified rabbit-anti-PR3 antibodies for detection. PR3-ANCA, myeloperoxidase (MPO)-ANCA, CRP and cystatin C were measured by routine methods. PR3 was significantly raised (P < 0.0001) in vasculitis patients (median 560 micro g/l, range 110-3,940, n = 59) compared with healthy blood donors (350 micro g/l, 110-580, n = 30) as well as disease controls (360, 110-580, n = 46). No correlation was seen with disease activity, inflammation or renal function. The raised NGAL levels correlated strongly with decreased renal function (r = 0.8, P < 0.001). After correcting for this, slightly increased levels (110, 42-340, n = 59) were observed compared with healthy blood donors (81, 38-130, n = 25), but not compared with the disease controls (120, 57-260, n = 48). In the disease controls, there was a significant correlation between NGAL and proteinase 3 (r = 0.3, p < 0.05), but this was not the case in the vasculitis patients. Whether patients had PR3-ANCA or MPO-ANCA was of no significance. In our measurements, we found significantly raised levels of PR3 in plasma from patients with small vessel vasculitis, regardless of ANCA specificity. This was not due to decreased renal function, ongoing inflammation or neutrophil activation. Plausible mechanisms for this include defects in the reticuloendothelial system, genetic factors and selective neutrophil degranulation or leakage.
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PMID:Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. 1260 7

We studied the relation between the antipapain activity of cysteine proteinase inhibitors (CPI) and immunohistochemical staining for cystatin C, using anti-chicken cystatin antibodies, in the colorectal cancer tissues. In primary tumour tissues immuno-peroxidase reactivity was present in the cytoplasm and on the cell surface membranes. Sections of non malignant tissues showed no staining. The percentages of positive staining were greater for adenocarcinoma than carcinoma,100% and 77% respectively. Antipapain activity which was increased in malignant tissues in comparison to control, rose successively from well differentiated carcinomas through moderately to poor differentiated. Invasive adenocarcinomas had higher antipapain activity than noninvasive ones. The results indicated that immunohistochemical detection of cystatin using anti-chicken cystatin antibodies could be useful in studying the prognostic significance of cystatin C expression in colorectal cancer.
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PMID:Expression of cystatin C in clinical human colorectal cancer tissues. 1641 1


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