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)

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.
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PMID:Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis. 161 71

An abnormally low level of cystatin C in the cerebrospinal fluid is a diagnostic marker for the hereditary form of brain hemorrhage associated with amyloidosis that was first identified in Iceland. We developed an assay for cystatin C to use in the diagnosis of patients with cerebral amyloid angiopathy and brain hemorrhage. This test consists of a sandwich enzyme-linked immunosorbent assay using monoclonal mouse anticystatin C and polyclonal rabbit anticystatin C antibodies. The cystatin C level was assayed in cerebrospinal fluid samples from 29 patients with brain hemorrhage and 45 control patients with other neurological diseases. Fifteen patients with brain hemorrhage showed low cystatin C levels (less than or equal to 70 ng/ml) in a clinical setting in which the positive and negative findings were compatible with a diagnosis of cerebral amyloid angiopathy. Immunohistological examination of brain tissue obtained by biopsy from two of the 15 patients confirmed the diagnosis of cerebral amyloid angiopathy and identified the deposition of cystatin C and beta-protein. This enzyme-linked immunosorbent assay is simple to perform and may be useful for investigating patients suspected of having cerebral amyloid angiopathy with brain hemorrhage and the deposition of cystatin C.
Stroke 1991 Jul
PMID:Diagnosis of cerebral amyloid angiopathy by enzyme-linked immunosorbent assay of cystatin C in cerebrospinal fluid. 185 5

Brain tissue from 11 patients with cerebral amyloid angiopathy, changes of Alzheimer's disease, and variable degrees of subcortical leukoencephalopathy was examined by immunohistochemical methods, using primary antibodies to peptide segments representing portions of the Alzheimer A4 (beta-) peptide or gamma-trace peptide (seen most commonly in Icelandic patients with cerebral hemorrhage (hereditary cerebral hemorrhage with amyloidosis [HCHWA-I]). Variable A4 immunostaining was seen within cortical (and rarely white matter) parenchyma in the form of senile plaques (with or without central cores), and within capillary and arteriolar walls. Within individual patients, A4 deposits were often primarily parenchymal or vascular, and when they were vascular they tended to be more prominent in arteriolar than in capillary wall segments. Perivascular A4 deposits were often detected around strongly immunoreactive microvessels. Gamma-trace immunoreactivity was noted in many A4-positive microvessel walls, but staining was always less intense than with the anti-A4 antibody. We conclude that patients with severe cerebral amyloid angiopathy may show wide variation in the severity and topography of A4 deposits within brain parenchyma. A4 may colocalize with gamma-trace peptide, suggesting that A4 and gamma-trace forms of cerebral amyloid angiopathy may not be as biochemically distinctive as has been suggested. Other proteases or protease inhibitors may contribute to the pathogenesis of cerebral amyloid angiopathy or cerebral amyloid angiopathy-related stroke syndromes.
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PMID:Immunohistochemical study of cerebral amyloid angiopathy. III. Widespread Alzheimer A4 peptide in cerebral microvessel walls colocalizes with gamma trace in patients with leukoencephalopathy. 204 52

Cerebral amyloid angiopathy is a pathologic condition characterized by the deposition of amyloid in the walls of small vessels in the cerebral cortex and meninges. Intracerebral hemorrhage is common in persons with this condition, but pure subarachnoid or subdural hemorrhage is rarely seen. Recently, the existence of two types of amyloid proteins related to cerebral amyloid angiopathy, beta protein and cystatin C, has been reported, and immunohistochemical methods using antisera to these proteins have become available. We describe a patient with fatal subarachnoid hemorrhage presumably caused by beta protein-type cerebral amyloid angiopathy, which was demonstrated immunohistochemically by using a monoclonal antibody to a synthetic peptide corresponding to residues 8-17 of beta protein. We suggest that beta protein-type cerebral amyloid angiopathy is a possible etiologic factor in subarachnoid hemorrhage of unknown cause.
Stroke 1990 Mar
PMID:Cerebral amyloid angiopathy as a cause of subarachnoid hemorrhage. 230 74

Using immunohistochemical staining methods with antibodies to amyloid beta protein and human cystatin C, we examined cerebrovascular amyloid protein in the brains from 46 cases with cerebral amyloid angiopathy (seven with Alzheimer's disease, one with Down's syndrome, 18 with intracranial hemorrhage, 10 with cerebral infarction, and 10 elderly patients without any neurologic disorder). All cerebrovascular amyloid deposits in these 46 cases were consistently immunoreactive to anti-beta protein antibody. However, in nine cases some vascular walls with strong beta protein immunoreactivity also reacted less intensely with the anti-cystatin C antiserum. Of these nine cases, seven showed relatively heavy cerebrovascular amyloid deposition, and all seven had suffered a fatal subcortical hemorrhage presumably caused by cerebral amyloid angiopathy. Previous limited studies have suggested that the amyloid protein seen in elderly individuals with cerebral amyloid angiopathy is composed of beta protein. However, subcortical hemorrhage rarely occurs in such individuals. Our study shows that aged patients with different brain disorders commonly suffer from beta protein-type cerebral amyloid angiopathy, and we also suggest that the severity of beta protein-type cerebrovascular amyloid deposition is a fundamental factor in cerebral amyloid angiopathy-induced brain hemorrhage in the elderly. The nature of the cystatin C-immunoreactive substance in some of these vascular lesions is uncertain, but it might conceivably play an additional important role in the pathogenesis of brain hemorrhage in these cases.
Stroke 1990 Mar
PMID:Immunohistochemical characterization of cerebrovascular amyloid in 46 autopsied cases using antibodies to beta protein and cystatin C. 221 20

Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in the birefringent amyloid deposits of the small arteries in the cerebrum, cerebellum, and leptomeninges of 10 Icelandic individuals with hereditary cerebral hemorrhage with amyloidosis. Specimens from other organs were investigated in one of the patients, and amyloid angiopathy characterized by an immunoreactivity of cystatin C was found in a submandibular lymph node. No immunoreactivity of amyloid fibril protein AA, kappa or lambda immunoglobulin light chain, or prealbumin was observed. Significantly low cerebrospinal fluid concentrations of cystatin C were found in all 9 investigated individuals with hereditary cerebral hemorrhage with amyloidosis. The concentrations of beta 2-microglobulin, albumin, and IgG in the cerebrospinal fluid were within normal limits. Isoelectric focusing showed that cystatin C from the cerebrospinal fluid of 9 patients with hereditary cerebral hemorrhage with amyloidosis had an isoelectric point identical to that of normal individuals. This investigation demonstrates that hereditary cerebral hemorrhage with amyloidosis may be diagnosed by two laboratory methods: immunohistochemical investigation of cystatin C in brain tissue specimens and quantitation of cystatin C in cerebrospinal fluid.
Stroke
PMID:Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis. 243 60

Cerebral amyloid angiopathy (CAA) refers to a group of hereditary (hereditary cerebral hemorrhage with amyloidosis, HCHWA and sporadic (SCAA) disorders characterized by amyloid fibril deposition restricted to the leptomeningeal and cortical vasculature leading to recurrent hemorrhagic and/or ischemic accidents. On clinical and biochemical grounds, two forms of HCHWA can be distinguished. The amyloid subunit of the HCHWA of Icelandic origin is related to Cystatin C, while amyloid from patients of Dutch origin (HCHWA-D) is related to the beta-protein (or A4), the main component of vascular and plaque core amyloid in Alzheimer's disease (AD) and Down's syndrome (DS) [corrected]. SCAA is an increasingly recognized cause of stroke in normotensive individual amounting to 5-10% of all cerebrovascular accidents. We now report the isolation and partial amino acid sequence of the amyloid subunit from a case of SCAA and a new case of HCHWA-D. The recognition that a heterogeneous group of diseases are linked by similar pathological and chemical features suggests that diversity of etiological factors may promote a common pathogenetic mechanism leading to amyloid-beta (A beta) deposition, and open new ways of research in AD and CAA as they are related to dementia and stroke.
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PMID:Beta-protein deposition: a pathogenetic link between Alzheimer's disease and cerebral amyloid angiopathies. 305 68

Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.
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PMID:An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). 765 71

We describe a novel transthyretin mutation at codon 18 where Asp is replaced by Gly (D18G) in a Hungarian kindred. This mutation is associated with meningocerebrovascular amyloidosis, producing dementia, ataxia, and spasticity. Fifty different transthyretin mutations are related to amyloid deposition, typically producing a peripheral neuropathy or cardiac dysfunction. These symptoms are absent in this family. Up to now, amyloid-beta (A beta), cystatin C, and prion proteins have been known to be deposited as amyloid in the brain, leading to stroke or dementia. With this report we establish that transthyretin amyloid deposition can also produce central nervous system dysfunction as the major clinical symptom.
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PMID:Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G) 857 96

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of beta-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma. The disease is due to a point mutation at codon 693 of the amyloid precursor protein (beta PP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke. The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article.
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PMID:Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I--A review of clinical, radiologic and genetic aspects. 873 26


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