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)

In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear.
 ...
PMID:Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis. 161 71

In this work 42 patients with active Schistosoma mansoni infection and renal involvement were examined. Of these, 16 had asymptomatic proteinuria (group I) and 26 had the nephrotic syndrome (group II). Fifteen nonschistosomal patients with idiopathic nephrotic syndrome were included as control cases (group III). Renal biopsy specimens were obtained from all patients and controls. These were examined by light microscopy (LM), by direct immunofluorescence microscopy using antisera against human IgG, IgM, IgA, C3, C4, C1q, and fibrinogen, and by indirect immunofluorescence microscopy using monoclonal antibodies directed against the circulating schistosome antigens, circulating anodic antigen (CCA) and circulating cathodic antigen (CCA). Schistosomal-specific deposits were seen in the renal glomeruli in 24 of the 42 schistosomal patients but in none of the 15 control patients. Although schistosomal-specific deposits were seen in seven of the 16 patients presenting with asymptomatic proteinuria, no morphological changes could be seen by LM. On the other hand, schistosomal-specific deposits could be seen in the kidneys of 17 of the 26 patients presenting with the nephrotic syndrome. All but one specimen showed morphological changes when examined by LM. These were consistent with mesangioproliferative glomerulonephritis in seven, focal segmental glomerulosclerosis in five, mesangiocapillary glomerulonephritis in two, membranous glomerulonephritis in one, and focal segmental hyalinosis in one patient. The present study clearly suggests that (a) schistosomal-specific nephropathy does exist in human settings, (b) it is an immune complex disease, and (c) CAA and CCA are major responsible antigens.
 ...
PMID:Characterisation of kidney lesions in early schistosomal-specific nephropathy. 314 Jan 23

The structural abnormalities and functional characteristics of dysfunctional prothrombin variants in two new kindreds have been determined. Prothrombin Corpus Christi (family 1) was purified and found to have markedly reduced fibrinogen clotting activity, yet normal amidolytic and near-normal platelet aggregating activity. A transition (C to T) at nucleotide position 8885, present in the heterozygous form in affected family members, resulted in the substitution of Cys for Arg 382. This substitution results in the loss of a positive charge within the fibrinogen-binding exosite of thrombin, thus accounting for the observed functional defect. A heterozygous C to T transition was also present at position 19994 in other family members with a hypoprothrombinemic phenotype. This mutation results in the replacement of Gln 541 (CAA) by a premature stop codon (TAA). Prothrombin Dhahran (family 2) was found to have markedly reduced fibrinogen clotting activity, but normal amidolytic activity. Affected family members were found to have a G to A transition at nucleotide position 7312 resulting in the substitution of His for Arg 271. This substitution results in the abolition of a factor Xa cleavage site, yielding meizothrombin rather than thrombin, on activation of prothrombin Dhahran by factor Xa. All but one of the above mutations occur at CpG dinucleotides, thus further supporting the observation of a high incidence of CpG transitions in hereditary dysprothrombinemia. The significant bleeding tendencies of individuals homozygous for prothrombin Dhahran (prothrombin clotting activity 5% to 7%) contrast sharply with the absence of significant chronic bleeding in the proband expressing prothrombin Corpus Christi (prothrombin clotting activity 2%). Our findings underscore the capacity of thrombin to contribute to clinical hemostasis by mechanisms other than its fibrinogen clotting activity.
 ...
PMID:Genetic analysis and functional characterization of prothrombins Corpus Christi (Arg382-Cys), Dhahran (Arg271-His), and hypoprothrombinemia. 883 54

Gelsolin-related amyloidosis (familial amyloidosis, Finnish type) is a rare disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene mutation. Facial palsy, mild peripheral neuropathy, and corneal lattice dystrophy are characteristic, but atrophic bulbar palsy, ataxia of gait, and minor cognitive impairment may occur. In histological and immunohistochemical studies of the central nervous system in 4 patients with a G654A gelsolin mutation, we found widespread spinal, cerebral, and meningeal amyloid angiopathy, with deposition of gelsolin-related amyloid (AGel). Marked extravascular deposits occurred in the dura, spinal nerve roots, and sensory ganglia. The amyloid deposits were also variably immunoreactive for apolipoprotein E (ApoE), alpha1-antichymotrypsin (alpha1-ACT), and cystatin C (Cys C). Cerebral perivascular fibrinogen immunoreactivity was occasionally noted. The patients showed posterior column degeneration and diffuse loss of myelin in the centrum semiovale with perivascular accentuation. Postmortem magnetic resonance imaging, performed on 1 patient, showed white matter lesions, colocalizing with the histological abnormalities. Our study shows that deposition of AGel in the spinal and cerebral blood vessel walls, meninges, as well as spinal nerve roots and sensory ganglia is an essential feature of this form of systemic amyloidosis and may contribute to the central nervous system symptoms.
 ...
PMID:Gelsolin-related spinal and cerebral amyloid angiopathy. 1007 44

A database was established from human hemofiltrate (HF) that consisted of a mass database and a sequence database, with the aim of analyzing the composition of the peptide fraction in human blood. To establish a mass database, all 480 fractions of a peptide bank generated from HF were analyzed by MALDI-TOF mass spectrometry. Using this method, over 20000 molecular masses representing native, circulating peptides were detected. Estimation of repeatedly detected masses suggests that approximately 5000 different peptides were recorded. More than 95% of the detected masses are smaller than 15000, indicating that HF predominantly contains peptides. The sequence database contains over 340 entries from 75 different protein and peptide precursors. 55% of the entries are fragments from plasma proteins (fibrinogen A 13%, albumin 10%, beta2-microglobulin 8.5%, cystatin C 7%, and fibrinogen B 6%). Seven percent of the entries represent peptide hormones, growth factors and cytokines. Thirty-three percent belong to protein families such as complement factors, enzymes, enzyme inhibitors and transport proteins. Five percent represent novel peptides of which some show homology to known peptide and protein families. The coexistence of processed peptide fragments, biologically active peptides and peptide precursors suggests that HF reflects the peptide composition of plasma. Interestingly, protein modules such as EGF domains (meprin Aalpha-fragments), somatomedin-B domains (vitronectin fragments), thyroglobulin domains (insulin like growth factor-binding proteins), and Kazal-type inhibitor domains were identified. Alignment of sequenced fragments to their precursor proteins and the analysis of their cleavage sites revealed that there are different processing pathways of plasma proteins in vivo.
 ...
PMID:Composition of the peptide fraction in human blood plasma: database of circulating human peptides. 1034 67

Two siblings with hypofibrinogenemia have lifelong trauma-related bleeding. Recently, the brother experienced recurrent thrombosis after cryoprecipitate infusions following surgery. The sister had 6 miscarriages. Plasma clots in each were resistant to compression and fibrinolysis and were soluble in 5 M urea. Examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed only the presence of crosslinked gamma-gamma fibrin chain dimers without high polymers of alpha n. Fibrin clots contained an abnormal 35-kDa constituent recognized by an antibody to the mature fibrinogen Aalpha-chain residues 241-476 but not by antibodies to Aalpha219-348 or Aalpha349-406. DNA analysis revealed a heterozygous CAA-->TAA mutation at the codon for amino acid 328 of the Aalpha gene in these siblings and 2 asymptomatic family members. The Gln328stop mutation (fibrinogen Keokuk) predicted a 46% truncation and the production of a 35-kDa Aalpha chain. Analysis of purified fibrinogen revealed expression of the abnormal Aalpha chain in 4 family members but found no normal fibrinogen in the 2 hypofibrinogenemic patients. This paradox was resolved when they and their asymptomatic mother were found to be heterozygous for a second Aalpha mutation, a GT-->TT splice site mutation in intron 4 (IVS4 + 1 G> T). However, compound heterozygosity for both mutations was required for the expression of severe hypodysfibrinogenemia and for clinical symptoms.
 ...
PMID:Severe hypodysfibrinogenemia in compound heterozygotes of the fibrinogen AalphaIVS4 + 1G>T mutation and an AalphaGln328 truncation (fibrinogen Keokuk). 1461 74

The pathogenesis of ischemic coronary events involves degradation of the extracellular matrix in atherosclerotic lesions. The cysteine protease inhibitor cystatin-C may be involved in this phenomenon. The association of plasma cystatin-C with the incidence of myocardial infarction-coronary death and angina, was examined in a nested case-control (two controls per case) design within the prospective cohort study (Prospective Epidemiological Study of Myocardial Infarction (PRIME Study)) which included 9,758 men aged 50-59 years who were free of coronary heart disease (CHD) on entry and followed for a 5-year period. Three hundred and thirteen participants suffered myocardial infarction or coronary death (n = 159) or angina pectoris (n = 154) during follow-up. Cystatin-C was positively correlated with body mass index (BMI), low-density lipoprotein (LDL)-cholesterol, triglycerides and several inflammatory markers such as fibrinogen (r = 0.18), C-reactive protein (CRP) (r = 0.24), interleukin-6 (= 0.20), tumor necrosis factor-alpha (TNFalpha) (r = 0.27) and two TNFalpha receptors: TNFR1A (r = 0.43) and TNFR1B (r = 0.41); and negatively with high-density lipoprotein (HDL)-cholesterol (r = -0.25). After adjustment for traditional risk factors (age, diabetes, smoking, hypertension, BMI, triglycerides, LDL- and HDL-cholesterol), cystatin-C was significantly associated with the occurrence of the first ischemic coronary event. However, this association was no longer significant when CRP was included in the analysis. A decrease in glomerular filtration rate did not explain higher cystatin-C in cases than in controls. Cystatin-C appears to participate in the inflammatory phenomenon observed in the atherosclerotic process. Cystatin-C is not a more predictive risk marker of CHD than CRP or interleukin-6, but could be useful in detecting moderate chronic renal disease.
 ...
PMID:Plasma cystatin-C and development of coronary heart disease: The PRIME Study. 1604 22

We report a novel fibrinogen variant (fibrinogen Seoul II), which has a heterozygous point mutation from CAA to CCA leading to AalphaGln328Pro. The mutation site is among several glutamine residues that serve as alpha-chain cross-linking acceptor sites. Fibrinogen Seoul II was found in a 51-year-old male patient and his family in Seoul, Korea. The patient was diagnosed with myocardial infarction at age 43. Eight years later he was admitted to the emergency room due to recurrence of the disease, where he expired under treatment with tissue plasminogen activator (t-PA). Fibrin polymerization curves, made using purified fibrinogen from the patient's relatives, showed a decreased final turbidity, suggesting Seoul II fibrin clots are composed of thinner fibers. This supposition was verified using scanning electron microscopy. Alpha-polymer formation by the mutant fibrinogen upon thrombin treatment in the presence of factor XIII and calcium was distinctly impaired. This result confirms that the residue Aalpha328 plays a pivotal role in alpha-chain cross-linking.
 ...
PMID:A novel fibrinogen variant (fibrinogen Seoul II; AalphaGln328Pro) characterized by impaired fibrin alpha-chain cross-linking. 1673 2

Although metabolic anomalies are often seen in advanced chronic kidney disease (CKD), their presence in more mild states is unknown. We studied 6722 participants in the Third National Health and Nutrition Examination Survey, dividing them into three mutually exclusive groups consisting of those having a normal or mildly reduced estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease (MDRD) formula), those with normal or elevated serum cystatin C, and those with clinically relevant moderate or severely reduced eGFR (stage 3 or 4 of CKD). The prevalence of several metabolic abnormalities associated with moderate to advanced CKD was determined after standardization for age, race-ethnicity, and gender. In the absence of stage 3 or 4 CKD, patients with elevated serum cystatin C had a higher prevalence of low hemoglobin and elevated uric acid, homocysteine, phosphorus, fibrinogen, and C-reactive protein than patients with a normal serum cystatin C. Our results show that in adults with normal or mildly reduced eGFR, elevated serum cystatin C is associated with an increased prevalence of metabolic abnormalities traditionally found in moderate or severe CKD. Elevated serum cystatin C may identify patients with 'preclinical' kidney disease not detected by traditional serum creatinine measurements.
 ...
PMID:Metabolic abnormalities are present in adults with elevated serum cystatin C. 1929 2

Recent studies suggest that serum cystatin C level is not only a sensitive marker for renal dysfunction but also a predictive marker for cardiovascular disease (CVD). However, the mechanism of this connection is not fully understood. We aimed to determine whether insulin resistance or various biomarkers of cardiovascular risk have a role in the link between cystatin C and CVD in type 2 diabetes mellitus patients. Anthropometric measurements and biochemical studies including inflammatory biomarkers were performed in 478 patients with type 2 diabetes mellitus. The degree of insulin resistance was assessed by homeostasis model assessment (HOMA-IR) and indicators of metabolic syndrome. Estimated glomerular filtration rate (eGFR) was derived from the Modification of Diet in Renal Disease study equation. After adjusting for age, sex, body mass index, and eGFR, the cystatin C level increased significantly in proportion to the number of metabolic syndrome components present (1.08 +/- 0.06, 1.19 +/- 0.04, 1.20 +/- 0.04, 1.23 +/- 0.04, and 1.37 +/- 0.06 mg/L; P < .0001); and HOMA-IR increased significantly in proportion to cystatin C quartiles (1.16 +/- 0.15, 1.40 +/- 0.13, 1.49 +/- 0.13, and 2.00 +/- 0.17; P < .0001) (means +/- SE). Albumin-creatinine ratio, fibrinogen, uric acid, homocysteine, high-sensitivity C-reactive protein, and lipoprotein(a) all showed significant correlations with cystatin C that were generally higher than those with eGFR. Cystatin C level was independently associated with HOMA-IR (beta = 0.0380, P = .0082), albumin-creatinine ratio (beta = 0.0004, P < .0001), uric acid (beta = 0.0666, P < .0001), and homocysteine (beta = 0.0087, P = .0004). In conclusion, cystatin C level was significantly associated with insulin resistance and biomarkers reflecting inflammation independent of renal function. These components may have a role in addition to that of eGFR in explaining the link between cystatin C and CVD in type 2 diabetes mellitus patients.
 ...
PMID:Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients. 1976 73


1 2 3 Next >>