Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane-bound nitrate reductase of Escherichia coli consists of three subunits designated as A, B, and C, with subunit C being the apoprotein of cytochrome b, A hemA mutant that cannot synthesize delta-aminolevulinic acid (ALA) produces a normal, stable, membrane-bound enzyme when grown with ALA. When grown without ALA, this mutant makes a reduced amount of membrane-bound enzyme that is unstable and contains no C subunit. Under the same growth conditions, this mutant accumulates a large amount of a soluble form of the enzyme in the cytoplasm. Accumulation of this cytoplasmic form begins immediately upon induction of the enzyme with nitrate. The cytoplasmic form is very similar to the soluble form of the enzyme obtained by alkaline heat extraction. It is a high-molecular-weight complex with a Strokes radius of 8.0 nm and consists of intact A and B subunits. When ALA is added to a culture growing without ALA, the cytoplasmic form of the enzyme is incorporated into the membrane in a stable form, coincident with the formation of functional cytochrome b. Reconstitution experiments indicate that subunit C is present in cultures grown without ALA but is reduced in amount or unstable. These results indicate that membrane-bound nitrate reductase is synthesized via a soluble precursor containing subunits A and B, which then binds to the membrane upon interaction with the third subunit, cytochrome b.
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PMID:Biosynthesis of membrane-bound nitrate reductase in Escherichia coli: evidence for a soluble precursor. 77 Apr 17

Strokes due to atherosclerosis are the most prominent neurological disease affecting adults, and efforts to reduce stroke occurrence, in addition to stroke-risk reduction, will require insights into molecular mechanisms. Our studies showing abnormal metabolism of low and high density lipoproteins (LDL and HDL) in vivo and of RFLP in apoprotein AI, the major protein of HDL, in stroke-prone subjects suggest that greater exploration of fundamental mechanisms of atherothrombotic brain infarction (ABI) should yield preventative strategies, the ultimate treatment for strokes.
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PMID:Molecular biological studies in atherothrombotic brain infarction. 135 86

After heart disease, cancer and stroke, Alzheimer's disease (AD) is the fourth major cause of death in the developed countries. Due to demographic changes, this situation will further worsen in the future. With the use of molecular biology techniques, important progress has recently been made in the understanding of the molecular changes leading to some forms of this disabling illness. The first step was the partial sequencing of the amyloid protein accumulating in the senile plaques and vascular deposits characteristic of AD. This allowed the cloning of a cDNA coding for a long amyloid precursor protein (APP). During the last few years, independent reports have described the presence of several reproducible point mutations in specific codons of APP in early onset familial Alzheimer patients. These mutations are responsible for an abnormal processing of APP, leading to the formation of pathological beta/A4 amyloid deposits. beta/A4 has been shown to possess neurotrophic properties in embryonic neurones and to be a potent neurotoxic agent in differentiated hippocampal neurones. More recently, modifications of intracellular calcium, activation of kinases, free radical generation and anomalies in potassium channels have been described as possible mechanisms of beta/A4 toxicity. Some forms of Apo-E lipoprotein may be an additional risk factor. Hence, it now seems possible to elaborate a coherent theory to explain the cascade of events leading to the development of AD. Genetically induced point mutations or environmental factors may produce a modification of the APP metabolism and processing. As a consequence, abnormal deposits of beta/A4 are formed. They may exert direct or indirect neurotoxic actions. A degeneration of cholinergic, catecholaminergic and other neurones follows, leading to the well known cognitive and behavioural changes of AD.
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PMID:Towards a pharmacological approach of Alzheimer's disease based on the molecular biology of the amyloid precursor protein (APP). 799 77

Apolipoprotein (apo) A-I is the major protein constituent of plasma high-density lipoproteins (HDL). HDL consist of two major classes of apoA-I-containing lipoproteins: LpA-I and LpA-I:A-II. LpA-I includes heterogeneous lipoprotein particles that differ in size and hydrated density. LpA-I was isolated by immunoaffinity chromatography from the fasting plasma of 24 normal human subjects and separated by gel filtration chromatography. Three major subclasses of LpA-I were eluted: large (Lg-LpA-I), medium (Md-LpA-I), and small LpA-I (Sm-LpA-I). By nondenaturing gradient PAGE, Lg-LpA-I, Md-LpA-I, and Sm-LpA-I had mean Strokes diameters of 10.8 +/- 0.5, 8.9 +/- 0.5, and 7.5 +/- 0.3 nm, respectively. The lipid/protein ratios were 1.25 +/- 0.12 for Lg-LpA-I, 0.75 +/- 0.10 for Md-LpA-I, and 0.38 +/- 0.08 for Sm-LpA-I. Lg-LpA-I was relatively lipid and cholesteryl ester rich compared with Md-LpA-I and Sm-LpA-I. Sm-LpA-I contained phospholipids as the major lipid component. ApoA-I was the major apolipoprotein in all LpA-I subfractions, whereas apoE was present only in Lg-LpA-I and apoA-IV was associated with both Md-LpA-I and Sm-LpA-I. All three LpA-I subclasses exhibited predominantly alpha mobility on agarose electrophoresis. Lg-LpA-I migrated as a diffuse band in the fast alpha position, whereas Md-LpA-I and Sm-LpA-I migrated to the slow alpha position.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical characterization of the three major subclasses of lipoprotein A-I preparatively isolated from human plasma. 824 Nov 25

Apolipoprotein E type 4 allele (apoE epsilon4) is associated with Alzheimer's disease (AD) in the late-onset familial form and in sporadic cases, but the age-associated risk in a randomly sampled elderly population is not established. We examined the association of apoE epsilon4 with AD and other dementias (mainly multi-infarct or dementia following stroke) in 1,030 persons aged 71 to 100 years in the population-based Framingham Study cohort. Kaplan-Meier survival analysis revealed that 55% of the apoE epsilon4/epsilon4 homozygotes developed AD by age 80, whereas 27% of apoE epsilon3/epsilon4 heterozygotes developed AD by age 85, and 9% of those without a 4 allele developed AD by age 85 years. In comparison with persons without a 4 allele, the risk ration for AD was 3.7 (95% CI = 1.9 to 7.5) for apoE epsilon3/epsilon4 heterozygotes and 30.1 (95% CI = 10.7 to 84.4) for apoE epsilon4 homozygotes. ApoE epsilon2 (2/2, 2/3, or 2/4 genotypes) was associated with an absence of AD. One-half (n=21) of the 43 AD patients were either homozygous or heterozygous for apoE epsilon4. We found evidence for an association of apoE epsilon4 with other dementia, primarily multi-infarct dementia and stroke. The risk ratio was 2.3 (95% CI = 0.9 to 6.1) for non-AD dementias among persons with apoE epsilon3/epsilon4. Although the apoE epsilon4 allele is a potent risk factor for AD and may be associated with other forms of dementia, most apoE epsilon4 carriers do not develop dementia, and about one-half of AD is not apoE epsilon4 associated. The low positive predictive value of this marker (0.10) suggest that use of apoE genotyping as a screening test for AD is not supported.
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PMID:Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study. 861 65

The authors report their experience regarding the identification of Apo-E alleles on atheroma carotid plaques in 20 patients of both sexes diagnosed as suffering from severe carotid stenosis using Doppler tests. A DNA hybridization and amplification method was used to identify Apo E-2, Apo E-3 and Apo E-4 alleles and their various phenotypical combinations. The following results were obtained in the 20 plaques examined: Apo E-3/E-4 in 114 patients (70%), 2 diabetic patients Apo E-4/E-3, one vascular demented patient Apo E-2/E-3, and 3 plaques defined as severely calcified Apo E-2/E-2. It can therefore be seen that the majority of plaques (70%), considered a risk for future stroke due to altered carotid Doppler tests, does not differ greatly by the homozygote allele Apo E-3/E-3 commonly found in the blood of the so-called "normal" population. It is difficult to draw any conclusions from the alleles found in the other 5 patients due to their scarce statistical value and the limited number of carotid plaques examined, but there appears to be some sort of correlation between calcified plaque, hyperlipidemia and the allele Apo E-2/E-2, with an interchange of position between cysteine arginine amino acids in the Apo E sequences.
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PMID:[Atheroma plaque and Apo E alleles]. 876 17

1. Effects of sesamin and episesamin (an epimer of sesamin) on lipid metabolism, in particular cholesterol metabolism, were examined in normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypertensive rats (SHRSP). 2. In normocholesterolaemic SHRSP fed a regular diet, both sesamin and episesamin significantly increased the concentration of serum total cholesterol, which was due to an increase of high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL). In addition, both substances effectively decreased serum very low density lipoprotein (VLDL). In the liver, only episesamin significantly decreased the activity of microsomal acyl-CoA:cholesterol acyltransferase. 3. In hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet), only episesamin improved serum lipoprotein metabolism with an increase in apoA-I and a decrease in apoB. In the liver, both sesamin and episesamin significantly suppressed cholesterol accumulation. Interestingly, only episesamin significantly increased the activity of microsomal cholesterol 7alpha-hydroxylase. 4. These results indicate that sesamin may be effective in preventing cholesterol accumulation in the liver. In comparison with sesamin, episesamin may be effective in the regulation of cholesterol metabolism in the serum and liver.
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PMID:Sesame lignans modulate cholesterol metabolism in the stroke-prone spontaneously hypertensive rat. 907 6

1. Gemfibrozil (Lopid) is extensively used as lipid-regulating agent in the Western World, and its beneficial effect is demonstrated in human studies such as the Helsinki Heart Study. However, the mechanism of its hypolipidaemic action is not fully understood. In the present paper, to elucidate the hypolipidaemic mechanism, we examined the effects of gemfibrozil on lipid metabolism in the normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypersensitive rat (SHRSP). 2. Gemfibrozil effectively increased high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL) and significantly decreased very low density lipoprotein (VLDL) in normocholesterolaemic SHRSP. In the liver of normocholesterolaemic SHRSP, gemfibrozil significantly reduced the activity of microsomal acyl-CoA:cholesterol acyltransferase. 3. Gemfibrozil markedly reduced atherogenic beta-very low density lipoprotein (beta-VLDL) and low density lipoprotein (LDL) in hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet). On the other hand, it significantly increased the contents of apoA-I, A-IV and E in the HDL fraction compared with the control group, suggesting that gemfibrozil effectively increases anti-atherogenic HDL subfractions rich in apoA-I, A-IV or E. In the liver of hypercholesterolaemic SHRSP, gemfibrozil markedly prevented lipid accumulation.
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PMID:Lipid-regulating action of gemfibrozil in the stroke-prone spontaneously hypertensive rat. 907 7

The Austrian Stroke Prevention Study recruited 1960 randomly selected subjects aged 50 to 75 years during a 3-year period of enrollment. The response rate of the study was 32.4%. A telephone interview with 200 randomly selected non-responders yielded no differences to responders regarding the frequency of major vascular risk factors known to the subjects. Besides demographics, the study assessed arterial hypertension, diabetes mellitus, cardiac disease, smoking, a complete lipid status including the apolipoprotein-E genotype, serum fibrinogen and anticardiolipin antibodies as well as various natural antioxidants such as vitamins A, C, E and beta-carotene. Arterial hypertension, diabetes mellitus, cardiac disease and hypercholesterolemia > 200 mg/dl were strikingly common and occurred in 38%, 7.6%, 32% and 76%, respectively. Suboptimal plasma concentrations of vitamin A, E, and beta-carotene were noted in 77.2%, 56.1% and in 53.2% of study participants. The rate of treatment of major risk factors known to the subjects prior to study entry were 60.3% and 70% for arterial hypertension and diabetes mellitus, but only 37.1% and 6.3% for cardiac disease and hypercholesterolemia > 250 mg/dl. Diet was commonly used to treat diabetes but was almost neglected in the treatment of other vascular risk factors. These data provide an orientation on the prevalence of risk factors and the use of primary preventive measures for stroke treatment in our community.
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PMID:[Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]. 913 70

Hypertension is more common among African Americans than Americans of European descent. However, the genetic etiology has not been defined. Similarly, lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is higher among African Americans. To explore the relationship between Lp (a) and hypertension, we measured the blood pressure of transgenic mice expressing apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we also determined blood pressure for apoE deficient mice, low density lipoprotein-receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression was not associated with hypertension. Surprisingly, LDL-R deficient mice exhibited male-associated hypertension. This observation could explain the higher incidence of atherosclerosis in male LDL-R deficient mice and human familial hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to photochemically induced cerebral stroke. However, this hypersensitivity was only modestly associated with sexual dimorphism. The presented data suggest that LDL-R deficiency results in hitherto unrecognized changes in the vascular tone.
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PMID:Male-associated hypertension in LDL-R deficient mice. 964 16


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