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

Cerebral amyloid angiopathies are defined by the presence of amyloid substance in the walls of cerebral vessels. All amyloid substances have a particular physico-chemical structure, which imparts certain specific staining properties, but the biochemical composition of different amyloid types varies. Different forms of cerebral amyloid angiopathy have been identified, based on the biochemical nature of the protein deposited (e.g. beta-amyloid, cystatin C, transthyretin, gelsolin, amyloid protein Bri, prion protein). Some cerebral amyloid angiopathies are familial; these prompted genetic studies which in turn led to a better understanding of the genes coding for different amyloid proteins. As a group, cerebral amyloid angiopathies have certain neuropathological lesions in common. Infiltration by amyloid substance results in weakening of the small vessel walls and secondary complications responsible for changes such as microinfarcts and miliary haemorrhages in the cerebral cortex, lobar haemorrhages and/or leucoencephalopathy. These changes form the basis of the neurological complications: meningeal and cerebral haemorrhages, transient ischaemic episodes, vascular dementia. However each type of hereditary cerebral amyloid angiopathy has individual clinical and histopathological features reflecting the severity of arterial involvement, the extent of amyloid deposition within or outside the central nervous system, and the association with other neurodegenarative changes.
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PMID:[Hereditary cerebral amyloid angiopathies]. 1188 14

Cerebral amyloid angiopathy (CAA) is the term used to describe deposition of amyloid in the walls of arteries, arterioles and, less often, capillaries and veins of the central nervous system. CAAs are an important cause of cerebral hemorrhage and may also result in ischemic lesions and dementia. A number of amyloid proteins are known to cause CAA. The most common sporadic CAA, caused by A beta deposition, is associated with aging and is a common feature of Alzheimer disease (AD). CAA occurs in several familial conditions, including hereditary cerebral hemorrhage with amyloidosis of Icelandic type caused by deposition of mutant cystatin C, hereditary cerebral hemorrhage with amyloidosis Dutch type and familial AD with deposition of either A beta variants or wild-type A beta, the transthyretin-related meningo-vascular amyloidoses, gelsolin as well as familial prion disease-related CAAs and the recently described BRI2 gene-related CAAs in familial British dementia and familial Danish dementia. This review focuses on the morphological, biochemical, and genetic aspects as well as the clinical significance of CAAs with special emphasis on the BRI2 gene-related cerebrovascular amyloidoses. We also discuss data relevant to the pathomechanism of the different forms of CAA with an emphasis on the most common A beta-related types.
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PMID:Sporadic and familial cerebral amyloid angiopathies. 1214 3

The feasibility of multi-affinity ligand surfaces in biomolecular interaction analysis-mass spectrometry (BIA/MS) was explored in this work. Multi-protein affinity surfaces were constructed by utilizing antibodies to beta-2-microglobulin, cystatin C, retinol binding protein, transthyretin, serum amyloid P and C-reactive protein. In the initial experiments, all six antibodies were immobilized on a single site (flow cell) on the sensor chip surface, followed by verification of the surface activity via separate injections of purified proteins. After an injection of diluted human plasma aliquot over the antibodies-derivatized surfaces, and subsequent MALDI-TOF MS analysis, signals representing five out of the six targeted proteins were observed in the mass spectra. Further, to avoid the complexity of the spectra, the six proteins were divided into two groups (according to their molecular weight) and immobilized on two separate surfaces on a single sensor chip, followed by an injection of human plasma aliquot. The resulting mass spectra showed signals from all proteins. Also, the convolution resulting from the multiply charged ion species was eliminated. The ability to create such multi-affinity surfaces indicates that smaller-size ligand areas/spots can be employed in the BIA/MS protein interaction screening experiments, and opens up the possibilities for construction of novel multi-arrayed SPR-MS platforms and methods for high-throughput parallel protein interaction investigations.
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PMID:Design and use of multi-affinity surfaces in biomolecular interaction analysis-mass spectrometry (BIA/MS): a step toward the design of SPR/MS arrays. 1255 34

The utility of biomolecular interaction analysis-mass spectrometry (BIA/MS) in screening for protein-protein interactions was explored in this work. Experiments were performed in which proteins served as ligands for screening of possible interactions with other proteins from human plasma and urine. The proteins utilized were beta-2-microglobulin, cystatin C (cysC), retinol binding protein (RBP), transthyretin (TTR), alpha-1-microglobulin, C-reactive protein, transferrin and papain. The immobilization of functionally active proteins was confirmed via interactions with antibodies to the corresponding proteins. Various dilutions of human urine and plasma were injected over the protein-derivatized surfaces. It was observed that the urine injections generally yielded smaller SPR responses than those observed after the plasma injections. The BIA/MS experiments did not reveal novel protein-protein interactions, although several established interactions (such as those between RBP and TTR, and cysC and papain) were validated. Few protein ligand deficiencies (such as truncations) leading to false negative and false positive BIA/MS results were also discovered.
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PMID:Delineating protein-protein interactions via biomolecular interaction analysis-mass spectrometry. 1255 33

Reported here, human urine samples were analyzed for beta-2-microglobulin (beta2m), transthyretin (TTR), cystatin C, urine protein 1 (UP1), retinol binding protein (RBP), albumin, transferrin, and human neutrophil defensin peptides (HNP) using mass spectrometric immunoassay (MSIA). MSIA is a unique analytical technique, which allows for the generation of distinct protein profiles of specific target proteins from each subject, which may be subsequently used in comparative protein expression profiling between all subjects. Comparative profiling allows for the rapid identification of variations within individual protein expression profiles. Although the majority of analyses performed in this study revealed homology between study participants, roughly one-quarter showed variation in the protein profiles. Some of these observed variants included a point mutation in TTR, absence of wild-type RBP, monomeric forms UP1, a novel beta2m glycated end product and altered HNP ratios. MSIA has been previously used in the analysis of blood proteins, but this study shows how MSIA easily transitions to the analysis, of urine samples. This study displays how qualitative urine protein differentiation is readily achievable with MSIA and is useful in identifying proteomic differences between subjects that might be otherwise overlooked with other analytical techniques due to complexity of the resulting data or insufficient sensitivity.
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PMID:Comparative urine protein phenotyping using mass spectrometric immunoassay. 1271 33

We investigated the relationship between the levels of serum albumin (ALB), serum transthyretin (TTR) or retinol binding protein (RBP) and those of serum cystatin C or clinical gradings in patients with diabetic nephropathy. Serum samples were obtained from 85 patients with type 2 diabetic nephropathy in our hospital. The levels of serum ALB, TTR, RBP and cystatin C were measured by the Dade Behring assay system using the automated Dade Behring Nephelometer II (BN II). The grades of diabetic nephropathy were classified into five groups according to Report of the Ministry of Health and Welfare, Japan. The serum levels of RBP showed a significant correlation between the serum levels of cystatin C and the grades of diabetic nephropathy. However, the serum levels of TTR were not significantly correlated with those of serum cystatin C or the grades of diabetic nephropathy. In this study, the serum levels of TTR were not influenced by renal function although those of RBP and ALB were influenced by renal function. In spite of clinical usefulness in the nutritional assessment of healthy controls and hemodialysis patients, RBP and ALB are not suitable nutrition marker in patients with chronic renal failure. However, TTR is suitable marker in patients with chronic renal failure.
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PMID:[Effective usage of nutrition assessment proteins in patients with diabetic nephropathy]. 1505 7

The IFCC Committee on Plasma Proteins has been investigating regional differences for commonly assayed plasma proteins to determine whether universal reference intervals can be applied. As a part of this study, we launched an Asian project analyzing the concentrations of 13 serum proteins whose values are standardized to CRM470, and five newer analytes: retinol-binding protein (RBP), cystatin C (CysC), light-chain-kappa (L-kappa), and light-chain-lambda (L-lambda). In Tokyo, Seoul, Kuala Lumpur, Hong Kong, Taipei and Shanghai, serum samples were collected from 146 to 415 apparently healthy individuals with nearly equal gender ratios. All assays were performed in Tokyo on a Behring Nephelometer II (BN II). Seven chemical analytes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gammaGT), creatinine, total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)) were also measured. These results were used for excluding individuals with possible latent clinical disorders. Positive acute phase reactants were consistently lower, and negative ones were higher, in Tokyo than those in other cities. The most conspicuous difference was observed in C-reactive protein (CRP). There were no regional differences in transferrin, albumin, or CysC. Creatinine was much lower in Tokyo despite comparable CysC levels. ALT and gammaGT were higher in Shanghai, Taipei and Seoul; gammaGT and TG were higher in Shanghai; and HDL-C was higher in Tokyo. Gender-related differences in reference intervals were observed for immunoglobulin (Ig)M, haptoglobin, RBP, transferrin, alpha2-macroglobulin (A2M), transthyretin, alpha1-acid glycoprotein, CysC, and C4 in all cities. Slight age-related differences were observed, irrespective of the region, in IgA and ceruloplasmin (increase) and A2M (decrease). Environmental factors and lifestyle seem to have a great influence on many commonly measured analytes.
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PMID:Diagnostic and epidemiological implications of regional differences in serum concentrations of proteins observed in six Asian cities. 1532 16

Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid deposition, associated with intracerebral hemorrhage and other cerebrovascular disorders and dementia. Several types of CAA have been identified in association with various amyloid proteins including amyloid beta protein (Abeta), cystatin C, prion protein, ABri/ADan, transthyretin, and gelsolin. Hereditary forms of CAA are associated with mutations in the genes coding these proteins or their precursors. Sporadic CAA of Abeta type is most common in elderly individuals as well as patients with Alzheimer disease (AD). Several gene polymorphisms have been reported to be associated with sporadic CAA or CAA-related hemorrhage, including apolipoprotein E (APOE), presenilin 1 (PS1), and alpha1-antichymotrypsin (ACT). As for the APOE, which has been well studied for CAA as well as AD and Abeta deposition, the epsilon4 allele is found to be associated with CAA, and the epsilon2 with CAA-related hemorrhage. Recently, we investigated whether gene polymorphisms of neprilysin (NEP), an Abeta-degrading enzyme, and the transforming growth factor (TGF)-beta1 (TGF-beta1), a multifunctional cytokine implicated in Abeta deposition, are associated with sporadic CAA. Concerning a GT repeat polymorphism in the enhancer/promoter region of the NEP, the shorter repeat alleles were associated with the CAA severity. The T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was also associated with the severity of CAA. These data suggest that multiple gene polymorphisms, including molecules related to the Abeta cascade, could be associated with the risk of sporadic CAA.
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PMID:Cerebral amyloid angiopathy and gene polymorphisms. 1553 17

This investigation describes the discovery of novel possible cerebrospinal fluid (CSF) biomarkers for frontotemporal dementia (FTD) using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Sixteen clinically diagnosed FTD patients and 12 non-demented controls were included in the study. CSF was collected and analyzed for protein expression by SELDI-TOF MS. The samples were analyzed on four different array surfaces using two different energy-absorbing molecules as matrices. In total each sample was subjected to eight different surface/matrix conditions. About 2000 protein peaks (mass/charge ratios) were detected. Forty-two peaks were differentially expressed in FTD (P < 0.01). After exclusion of peaks with low signal-to-noise ratio and/or poor resolution and peaks representing differentially charged proteins, 10 peaks remained, five of which were increased and five decreased in FTD cases compared to controls. Using partial least square discriminant analysis (PLS-DA), the combination of these biomarkers discriminated FTD from non-demented controls with a sensitivity of 94%, a specificity of 83% and an accuracy of 89%. Five of the peaks were purified further and identified by tandem MS as a fragment of neurosecretory protein VGF, transthyretin, S-cysteinylated transthyretin, truncated cystatin C and a fragment of chromogranin B. With use of these potential biomarkers, FTD can be distinguished from control subjects with high accuracy in this pilot study.
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PMID:Identification of CSF biomarkers for frontotemporal dementia using SELDI-TOF. 1615 29

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS.
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PMID:Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. 1631 19


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