Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated.
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PMID:Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. 1 Jul 36

Hereditary cerebral amyloid angiopathy has been described in Icelandic and Dutch families. Although the clinical manifestations show similarities, biochemical characterization revealed that amyloid in the Icelandic patients consists of cystatin C and in the Dutch patients of beta-protein. Both diseases are caused by a single base mutation leading to the same amino acid (viz. glutamine). Furthermore, both cystatin C and the beta-protein precursor are protease inhibitors. Therefore, the mechanism of amyloidogenesis may be similar in both diseases. A comparison of clinical, pathological, genetic, and biochemical aspects of these two types of hereditary cerebral amyloid angiopathy is presented.
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PMID:Comparison between the Icelandic and Dutch forms of hereditary cerebral amyloid angiopathy. 132 May 29

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

An amyloid protein that precipitates in the cerebral vessel walls of Dutch patients with hereditary cerebral hemorrhage with amyloidosis is similar to the amyloid protein in vessel walls and senile plaques in brains of patients with Alzheimer's disease, Down syndrome, and sporadic cerebral amyloid angiopathy. Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the amyloid protein. The mutation may account for the deposition of this amyloid protein in the cerebral vessel walls of these patients, leading to cerebral hemorrhages and premature death.
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PMID:Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. 211 84

Amyloid fibrils deposited in cerebral vessel walls in Dutch patients with hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) are formed by polymerization of a 39-residue peptide similar to the beta-protein of Alzheimer's disease, Down syndrome, sporadic cerebral amyloid angiopathy and normal aging. Sequence analysis of genomic DNA in HCHWA-D patients demonstrated a point mutation, cytosine for guanine at position 1852 of the precursor beta-protein gene, which causes a single amino acid substitution (glutamine for glutamic acid) corresponding to position 22 of the amyloid protein. The normal allele was also present in these patients. To examine the expression of normal and variant beta-protein alleles in HCHWA-D we analyzed all the tryptic peptides obtained from several amyloid fractions from leptomeningeal vascular walls. Amino acid sequence of two peptides (T3a and T3b) with identical amino acid composition revealed that T3a had glutamine and T3b had glutamic acid at position 22. Thus both the normal and variant Alzheimer's beta-protein alleles are expressed in vascular amyloid in HCHWA-D and may be detected by tryptic peptide mapping. Moreover, we have developed a diagnostic assay for high risk populations and prenatal evaluation that is based on the existence of the mutation.
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PMID:Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. 219 78

Consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients. In this study the direct effects of glutamate and its metabolite, glutamine, on arterial contractility were examined using rings of rabbit aorta. In a high concentration glutamate caused significant concentration-dependent contractions (EC50, 10(-1)M; maximum tension, 188.4 +/- 33.3 mg wt tension/mg tissue). Agonists and antagonists for alpha-adrenergic, histaminergic, serotonergic, cholinergic, and GABA-nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions. At high concentrations (10(-5)M) the calcium channel blocker, verapamil, inhibited the glutamate response. Glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine (NE), phenylephrine (PE), histamine, serotonin (5-HT), and prostaglandin F2 alpha (PGF2 alpha)-induced contractions. Kainic acid (10(-4)M), an agonist of one subpopulation of central glutamate receptor, potentiated glutamate-induced vasoconstriction; a higher concentration (10(-3)M) produced an irreversible inhibition of glutamate contractility. Only the central glutamate receptor antagonist, ketamine (10(-4)-10(-2)M), induced a reversible, concentration dependent inhibition of glutamate-induced contractions. Glutamate contractility was not dependent on extracellular calcium, an intact endothelium or neuronal function. These results demonstrate a direct effect of glutamate on peripheral arterial tone. Dietary consumption of large quantities of MSG may represent a serious health hazard to certain individuals with pre-existing vascular disease.
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PMID:Vasospasm contributes to monosodium glutamate-induced headache. 226 10

As a comparison to previous analyses of purified amyloid plaque cores from Alzheimer's disease (AD) brain, we performed protein chemical and immunocytochemical studies on amyloid filaments extracted from meningeal blood vessels of patients with Alzheimer's disease. Results were compared with those obtained from identically prepared fractions of aged normals without cerebral amyloid angiopathy or other microscopic findings of AD. The amyloid isolation method of Glenner and Wong was modified, including an extraction with sodium dodecyl sulfate (SDS). Gel electrophoresis of purified amyloid from AD meninges yielded bands centered at 4.2 kDa. Sequencing of the HPLC-purified amyloid protein from AD meninges confirmed the published beta-protein sequence for residues 1-30 and 35-40, with the exception of glutamic acid rather than glutamine at position 11. N-terminal heterogeneity was not prominent. No sequence beyond residue 40 was obtained. Proteins of similar but not identical mol. wt. were present in HPLC-purified fractions of normal meninges; neither the beta-protein sequence nor any other interpretable sequence was detected in such fractions. Two antisera raised against the purified AD meningovascular amyloid protein identified the 4.2 kDa band on Western blots of AD preparations; no protein band in this region was labeled in control preparations. The 4.2 kDa band in AD meningeal preparations was also lableled by an antiserum to synthetic beta-peptide but not by an antiserum to the carboxyl terminus of the beta-protein precursor. Both the AD meningovascular amyloid antisera selectively labeled amyloid in cortical and meningeal vessels and plaque cores; tangles, plaque neurites, and cells of normal CNS and numerous non-neural tissues were unstained. The antisera also labeled the occasional deposits of vascular amyloid and less frequent plaque core amyloid found in some aged individuals without AD. We conclude that (1) the meningovascular amyloid beta-protein of AD, whose sequence has been confirmed and extended to residue 40, was not immunocytochemically detectable in neurofibrillary tangles; (2) beta-protein could not be detected in meningeal preparations from aged controls who lack light microscopically visible meningovascular amyloid; and (3) the vascular and plaque core amyloid present in aged normals is antigenically cross-reactive with AD meningovascular amyloid.
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PMID:Protein chemical and immunocytochemical studies of meningovascular beta-amyloid protein in Alzheimer's disease and normal aging. 321 3

Hereditary CNS amyloid angiopathy occurring in Icelanders is the first human disorder known to be caused by deposition of cystatin C amyloid fibrils in the walls of the brain arteries leading to single or or multiple strokes with fatal outcome. One or more affected members have been verified by histological examination in 8 families containing 127 affected. These originated from the same geographic area. Abnormally low value of cystatin C found in the cerebrospinal fluid of those affected can be used to support or make diagnosis of this disease, also in asymptomatic relatives. By amino acid sequence analysis the amyloid fibrils in the patients are found to be a variant of cystatin C (gamma-trace), a major cysteine proteinase inhibitor. The variant protein has an amino acid substitution (glutamine for leucine) at position 58 in the amyloid molecule. It is postulated that a point mutation has occurred leading to production of amyloidogenic protein causing the disorder.
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PMID:Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage. 367 96

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.
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PMID:Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. 375 14

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder characterized by the deposition of amyloid in most investigated tissues. The main component of the amyloid deposits is a variant of the cysteine proteinase inhibitor cystatin C, and the most serious consequence of the disease is that amyloid deposition in the cerebral arteries leads to a massive brain hemorrhage and death before 40 years of age. HCCAA has been shown to be caused by a T-->A point mutation in the codon for leucine at position 68 in exon 2 of the cystatin C gene, which results in a leucine-->glutamine amino acid substitution in the cystatin C molecule. Since the HCCAA-causing mutation abolishes an AluI restriction site in the cystatin C gene, analysis of this AluI restriction fragment-length polymorphism (RFLP) enables simple and accurate molecular diagnosis of HCCAA. One hundred ninety-one individuals have now been screened for the HCCAA causing mutation, including a fetus for prenatal diagnosis. Thirty-six individuals belonging to nine Icelandic families have been found to have the mutation and it is highly probable that these families descend from a common ancestor.
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PMID:Molecular diagnosis of hereditary cystatin C amyloid angiopathy. 809 19


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