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)

Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of young adults. A method for rapid and simple diagnosis of HCCAA is described. It is based upon oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. Loss of an AluI recognition site in the amplified DNA segment from HCCAA patients results in a deviating band-pattern at agarose gel electrophoresis, compared with that obtained from normal subjects or unaffected HCCAA family members. In a population of 9 patients with manifest HCCAA, 14 patients with other causes of brain hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single T----A substitution in the codon for amino acid residue 68 of cystatin C.
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PMID:Hereditary cystatin C amyloid angiopathy: identification of the disease-causing mutation and specific diagnosis by polymerase chain reaction based analysis. 135 69

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) (or familial cerebral amyloid angiopathy) and familial Alzheimer's disease (FAD) share several properties. Both are autosomal dominant forms of cerebral amyloidosis characterized by beta-amyloid (A beta) deposition. In HCHWA-D the A beta is predominantly found in blood vessels and in early parenchymal plaques, whereas in AD parenchymal A beta deposits in the form of senile plaques and neurofibrillary tangles are a more prominent finding. Point mutations in the amyloid precursor protein (APP) have recently been described, in both conditions. A G to C transversion at codon 618 (extracellular portion of APP695), producing a single amino acid substitution of glutamine instead of glutamine acid, occurs in HCHWA-D; whereas mutations at codon 642 in the intramembrane region of APP695 (phenylalanine, isoleucine, or glycine instead of valine) are associated with early onset FAD. This suggests that the site of particular mutations in the APP gene and the type of amino acid substitution in the APP holoprotein are more important in determining clinicopathological phenotype and age at which A beta is deposited. Thus FAD and HCHWA-D can be regarded as two sides of the same coin.
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PMID:Molecular biology of Alzheimer's amyloid--Dutch variant. 146 89

We studied the presence and morphology of plaque-like lesions in the frontal cortex of six patients, aged 40 to 76 years, with hereditary cerebral hemorrhage with amyloidosis--Dutch type (HCHWA-D), using beta/A4 immuno-, silver, Congo red and thioflavin S staining. Two types of beta/A4 immunoreactive and Congo red-negative plaques were detected. The first type was composed of argyrophilic fibrous material in periodic acid-methenamine silver (PAM) and modified Bielschowsky staining and lacked silver-stained degenerating neurites. Therefore, this type of plaque has the same staining properties as the diffuse plaque described in Alzheimer's disease, Down's syndrome and nondemented elderly. The second type of plaque, occurring only in the three oldest patients and numerically increasing with age, consisted of a spherical non-argyrophilic area of granular texture with a rim of PAM-positive material. The PAM-positive fibrous material of both types of plaques was mingled with coarser and compact, irregular-shaped argyrophilic structures in the oldest patient. The described plaques did not show bright fluorescence with thioflavin S staining. These results indicate, that the morphology of plaques, encountered in HCHWA-D, is diverse and changes with age.
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PMID:Morphology of cerebral plaque-like lesions in hereditary cerebral hemorrhage with amyloidosis (Dutch). 147 74

The amyloid beta-protein is a 39-42 amino acid peptide that is deposited in senile plaques and in cerebral vessel walls in individuals with Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), and, to a much lesser extent, normal aging. It is derived from abnormal proteolytic processing of its parent protein, the amyloid beta-protein precursor. Here we show that individuals with the HCHWA-D mutation and clinically manifesting the disease have markedly decreased cerebrospinal fluid levels of soluble amyloid beta-protein precursor (0.7 +/- 0.4 micrograms/ml) compared with age-matched normal subjects (3.0 +/- 0.2 micrograms/ml) as determined by quantitative immunoblotting and enzyme-linked immunosorbent assays. Similarly, age-matched patients diagnosed with probable Alzheimer's disease also have decreased cerebrospinal fluid levels of soluble amyloid beta-protein precursor (1.0 +/- 0.3 micrograms/ml). These parallel findings suggest a common biochemical marker for these two diseases and further establish the pathogenic relatedness of HCHWA-D and Alzheimer's disease.
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PMID:Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type share a decrease in cerebrospinal fluid levels of amyloid beta-protein precursor. 151 Mar 61

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

beta-Amyloid (A beta) deposition in fibril form is the central event in a number of diseases, including Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D). A beta is produced by degradation of a larger amyloid precursor protein (APP). Recently a mutation in the APP gene has been found in HCHWA-D causing a glutamine for glutamic acid substitution at residue 22 of A beta. The influence of this mutation on fibrillogenesis is not known, although it is clear that affected patients have accelerated cerebrovascular amyloid deposition, with disease symptoms early in life. We report the in vitro demonstration of accelerated fibril formation in a 28 residue synthetic peptide homologous to the Dutch variant A beta. Furthermore, in eight residue peptides homologous to A beta the presence of the mutation is necessary for fibril formation. These findings provide a mechanism for accelerated amyloid formation in the Dutch variant of APP.
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PMID:Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation. 195 95

Clinical, radiological, and immunohistochemical findings in brain biopsy specimens from six patients with cerebral amyloid angiopathy-associated intracerebral hemorrhage were reviewed. Acute clinical presentations included headache, nausea and vomiting, loss of consciousness, and focal neurological deficits such as hemiplegia and blindness. Transient ischemic attacks experienced by one patient and referable to one hemisphere did not indicate impending hemorrhage in that region. Computed tomographic scans revealed acute, irregular, superficial, lobar hemorrhage with occasional ring enhancement. Immunohistochemical studies were performed on biopsy specimens using primary antibodies against portions of the Alzheimer A4 (beta-) peptide or gamma-trace peptide (the vascular amyloid protein in patients with hereditary cerebral hemorrhage with amyloidosis-Icelandic type). In all patients, anti-A4 and anti-gamma-trace labeled cerebral microvessels. Immunoreactive senile plaques were few compared with the numbers of stained microvessels. Reactive astrocytes in some patients were labeled by both antiserum samples, suggesting uptake or production of these proteins by the astrocytes. This study demonstrates the heterogeneous clinical and radiological features of cerebral amyloid angiopathy-related brain hemorrhage and the value of anti-A4 and anti-gamma-trace immunohistochemical study of biopsy material from patients with suspected cerebral amyloid angiopathy-related intraparenchymal bleeding.
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PMID:Cerebral hemorrhage with biopsy-proved amyloid angiopathy. 172 64

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.
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PMID:Diagnosis of cerebral amyloid angiopathy by enzyme-linked immunosorbent assay of cystatin C in cerebrospinal fluid. 185 5

Human hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), an autosomal dominant form of cerebral amyloid angiopathy (CAA), is characterized by extensive amyloid deposition in the small leptomeningeal arteries and cortical arterioles, which lead to an early death of those afflicted in their fifth or sixth decade. Immunohistochemical and biochemical studies have indicated that the amyloid subunit in HCHWA-D is antigenically related to and homologous in sequence with the amyloid beta protein isolated from brains of patients with Alzheimer's disease and Down syndrome. The amyloid beta protein is encoded by the amyloid beta protein precursor (APP) gene located on chromosome 21. Restriction fragment length polymorphisms detected by the APP gene were used to examine whether this gene is a candidate for the genetic defect in HCHWA-D. The data indicate that the APP gene is tightly linked to HCHWA-D and therefore, in contrast to familial Alzheimer's disease, cannot be excluded as the site of mutation in HCHWA-D.
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PMID:Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). 197 58

Amyloidosis is a disease involving the fibrillar deposition of proteins in a manner that uniformly leads to the presence of green birefringence on polarization microscopy after staining the involved tissues with Congo red. In the year summarized, a wide range of new information has accumulated about this disease. In this article, attention has been paid to several newly described proteins now known to precipitate into amyloid deposits, including the proteins transthyretin, apolipoprotein A-1, cystatin C, gelsolin, amyloid beta protein, beta 2-microglobulin, scrapie protein, and islet amyloid polypeptide. The number of these amyloid-related proteins has resulted in the need for a revised nomenclature and classification scheme. The results of a recent international symposium addressing this issue are summarized in table form. The varied clinical manifestations of amyloidosis are described according to organ system, with unusual or unique areas of involvement noted. Finally, the treatment of amyloidosis and its prognosis are addressed, and new areas of possible intervention suggested.
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PMID:Amyloidosis. 204 38


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