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)

Two hundred and twelve cases of carotid surgery performed on patients presenting ipsilateral ischemic monophthalmic symptoms were retrospectively studied (OPH group). Among these, 125 had presented isolated ophthalmic pre-operative symptoms (OPHEX group) and 87 both ophthalmic and encephalic ischemic symptoms (OPHNEX group). During the same period, 702 cases of isolated carotid surgery were performed upon atherosclerotic patients without ipsilateral ischemic monophthalmic pre-operative symptoms (NOPH group). Among the cases of this latter group, 147 were performed upon asymptomatic patients (ASY group). 514 had presented isolated encephalic pre-operative symptoms (ENC group) and 41 had presented contralateral ischemic symptoms. The OPHNEX group presented a significantly increased peri-operative mortality and morbidity rate compared to the OPHNEX group (peri-operative deaths, lethal strokes, cardiac peri-operative morbidity) and compared to the ENC group than in the ASY group. The OPHNEX group presented a significantly increased long term mortality and morbidity rate compared to the OPHEX group (lethal strokes, all deaths). In the follow up, the OPH group presented, compared to the NOPH group, lower rates of non lethal stroke but higher rates of ophthalmic ischemic events (ipsi or contralateral) and higher rates of cardiac deaths. OPHEX, OPHNEX, ASY, ENC and NOPH groups presented significant differences as regards the general cardio-vascular and metabolic context, the macroscopy of carotid lesions operated upon, the topography and diffusion of other atherosclerotic lesions.
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PMID:[Carotid surgery for ophthalmic manifestations. Early and late results]. 248 50

Although controversial, data on the genetic polymorphism of apoprotein E (APOE), methylenetetrahydrofolate (MTHFR) and paraoxonase (PON1) genes implicate their role in the development of cerebrovascular disease. The aim of this study was to assess the association of polymorphism of APOE, MTHFR and PON1 genes in 56 stroke and 36 carotid stenosis patients, and in 124 control subjects by PCR-restriction fragment length polymorphism analysis. In the stroke group a significantly different MTHFR genotype distribution (p=0.004, odds ratio for T/T of 17.571), but no significant difference in APOE and PON1 allele and genotype distribution compared to the control was found. The carotid stenosis group exhibited a significantly different APOE allele and genotype distribution (p=0.023, odds ratio APOEepsilon3epsilon4 of 4.24), but no significant difference in the MTHFR and PON1 allele and genotype distribution from the control group. The preliminary results obtained in this study revealed an association of the MTHFR and APOE gene polymorphism with cerebrovascular disease, suggesting a significant risk for stroke in subjects who are homozygous for the T allele and for carotid stenosis in subjects having APOEepsilon3epsilon4 genotype. Additional studies in larger patient groups are needed to confirm these observations.
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PMID:Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. 2463 86

A 3-year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors and cognitive consequences of MRI white matter lesions (WML) in elderly individuals without neuropsychiatric disease. Lesion progression was found in 17.9% of individuals over a time period of 3 years. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline were the only significant predictors of white matter hyperintensity progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study provide first evidence for genetic susceptibility factors for progression of WML. We observed associations with the paraoxonase Leu-->Met 54 polymorphism and with the M235T polymorphism of the angiotensinogen gene. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period, but the statistical power of this analysis was low.
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PMID:Evolution of white matter lesions. 1190 Dec 38

As medicine moves into the 21st century, with added pressures of increasing costs and limited resources, successful reduction of the impact of stroke on the population will require shifting our emphasis away from treating end stages of generalized atherosclerosis and other underlying diseases to prevention of these diseases. However, before any potential interventions can be promoted with confidence, more needs to be known about the specific causes of stroke subtypes in various populations, especially potentially modifiable risk factors. In this selective review, we appraise current evidence on some markers of systemic inflammation (C-reactive protein), endothelial dysfunction (homocysteine, von Willebrand factor), dietary fatty acids and micronutrients as risk factors for stroke. Although a great deal of research into the role of these risk factors in cardiovascular diseases has been undertaken, little reliable information is available on their role in stroke, especially in the elderly. Evaluation of plasma fatty acids and specific antioxidants and micronutrients as well as markers of systemic inflammation, endothelial dysfunction (including C-reactive protein, homocysteine levels, von Willebrand factor, and paraoxonase activity) may prove to be valuable in the future determination of the risk of stroke.
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PMID:Systemic inflammation, endothelial dysfunction, dietary fatty acids and micronutrients as risk factors for stroke: a selective review. 1201 44

The past several years have been marked by significant progress in identifying genetic anomalies in stroke-prone probands. These advances have occurred in both highly penetrant single-gene disorders and in common stroke, which is influenced by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to diagnose because of the wide range of notch 3 mutations that can cause disease, but a new immunohistochemical technique using a skin biopsy sample appears to be highly sensitive and specific. In a landmark Icelandic study, linkage was established between stroke and a locus on chromosome 5q12 designated STRK1. Association studies continue to identify polymorphisms that predispose to stroke and to markers for cerebrovascular atherosclerosis, such as intima-media thickness. Intense interest now surrounds genes involved in inflammation, including genes that encode for the interleukin-1 receptor antagonist and paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment will incorporate genetic data to refine and individualize management of cerebrovascular disease.
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PMID:New advances in identifying genetic anomalies in stroke-prone probands. 1279 73

Arterial thrombosis is a complex disorder that involves multiple genetic and environmental factors interacting to produce the characteristic phenotype. In the past decades, investigators have focused on the molecular genetics of arterial vascular disorders and have identified numerous polymorphisms and mutations in genes related to the hemostatic system and to enzymes involved in the synthesis and bioavailability of nitric oxide (NO); however, the relation between most polymorphisms and the risk of coronary artery disease, ischemic stroke, and peripheral vascular disease remains highly controversial. In this review, we describe the most common genetic variations involved in the pathogenesis of arterial thrombosis, their functional implications, and their association with disease risk. Specifically, we consider polymorphisms in coagulation factors (fibrinogen, prothrombin, FV Leiden, FVII, and FXIII); fibrinolytic factors (tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor); platelet surface receptors; methylenetetrahydrofolate reductase; endothelial NO synthase; and the antioxidant enzymes paraoxonase and plasma glutathione peroxidase. Overall, there seems to be a modest contribution of individual genetic variants in the hemostatic and antioxidant systems to the risk of arterial thrombosis. Thus, future research ought to focus on identifying novel genetic determinants and on the interaction of these genetic risk factors with each other and the environment to understand better the pathobiology and susceptibility to arterial thrombotic disease.
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PMID:Genetic determinants of arterial thrombosis. 1461 95

The past several years have been marked by significant progress in identifying genetic anomalies in stroke-prone probands. These advances have occurred in both highly penetrant single-gene disorders and in common stroke, which is influenced by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to diagnose because of the wide range of notch 3 mutations that can cause disease, but a new immunohistochemical technique using a skin biopsy sample appears to be highly sensitive and specific. In a landmark Icelandic study, linkage was established between stroke and a locus on chromosome 5q12 designated STRK1. Association studies continue to identify polymorphisms that predispose to stroke and to markers for cerebrovascular atherosclerosis, such as intima-media thickness. Intense interest now surrounds genes involved in inflammation, including genes that encode for the interleukin-1 receptor antagonist and paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment will incorporate genetic data to refine and individualize management of cerebrovascular disease.
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PMID:New advances in identifying genetic anomalies in stroke-prone probands. 1532 9

An increased concentration of homocysteine is an important risk factor of atherosclerosis; however, the mechanism of the proatherogenic effect of this amino acid is not yet known. Studies performed during the last two decades suggest that the atherogenic effect of homocysteine may be accounted for by homocysteine thiolactone (HCTL). Homocysteine is nonspecifically activated by methionyl-tRNA synthetase; however, it is not transferred to tRNA and incorporated into proteins, but is transformed to a cyclic thioester, homocysteine thiolactone. HCTL is highly reactive and acylates free amino groups of protein lysine residues, the process referred to as protein N-homocysteinylation. Various plasma proteins are homocysteinylated in vitro and in vivo. Homocysteinylation results in the incorporation of additional thiol groups which may alter the physicochemical properties and biological activity of proteins. In particular, homocysteinylation of low-density lipoproteins (LDLs) increases their susceptibility to oxidation and accelerates their uptake by macrophages. In addition, homocysteinylated LDL elicit humoral immune response. Anti-homocysteinyllysine antibodies are detected in plasma of healthy humans and their titer is elevated in patients with ischemic heart disease or ischemic cerebral stroke. Homocysteine thiolactone is hydrolyzed to homocysteine by paraoxonase (PON), a calcium-dependent esterase synthesized in the liver and contained in plasma high-density lipoproteins (HDLs). Protein homocysteinylation may contribute to accelerated atherogenesis in individuals with hyperhomocysteinemia.
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PMID:Protein homocysteinylation: a new mechanism of atherogenesis? 1610 41

Leptin, a 167-amino acid peptide hormone produced by white adipose tissue, is primarily involved in the regulation of food intake and energy expenditure. Leptin receptors are expressed in many tissues including the cardiovascular system. Plasma leptin concentration is proportional to body adiposity and is markedly increased in obese individuals. Recent studies suggest that hyperleptinemia may play an important role in obesity-associated cardiovascular diseases including atherosclerosis. Leptin exerts many potentially atherogenic effects such as induction of endothelial dysfunction, stimulation of inflammatory reaction, oxidative stress, decrease in paraoxonase activity, platelet aggregation, migration, hypertrophy and proliferation of vascular smooth muscle cells. Leptin-deficient and leptin receptor-deficient mice are protected from arterial thrombosis and neointimal hyperplasia in response to arterial wall injury. Several clinical studies have demonstrated that high leptin level predicts acute cardiovascular events, restenosis after coronary angioplasty, and cerebral stroke independently of traditional risk factors. In addition, plasma leptin correlates with markers of subclinical atherosclerosis such as carotid artery intima-media thickness and coronary artery calcifications. Inhibition of leptin signaling may be a promising strategy to slow the progression of atherosclerosis in hyperleptinemic obese subjects.
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PMID:Leptin and atherosclerosis. 1658 Jun 76

Cell death is the basic neuropathological substrate in cerebral ischemia, and its non-invasive imaging may improve diagnosis and treatment for stroke patients. ApoSense is a novel family of low-molecular weight compounds for detection and imaging of cell death in vivo. We now report on imaging of cell death and monitoring of efficacy of neuroprotective treatment in vivo by intravenous administration of the ApoSense compound DDC (didansylcystine), in experimental stroke in rodents. Rats and mice were subjected to a short-term (2 h) or permanent occlusion of the middle cerebral artery (MCA) and injected with DDC or 3H-labeled DDC. Fluorescent and autoradiographic studies, respectively, were performed ex vivo, comprising assessment of DDC uptake in the infarct region, in correlation with tissue histopathology. Neuroprotection was induced by a caspase inhibitor (Q-VD-OPH), and its effect was monitored by DDC. Following its intravenous administration, DDC accumulated selectively in injured neurons within the region of infarct. Caspase inhibition exerted a 45% reduction in infarct volume, which was well reported by DDC. This is the first report on a small molecule probe for detection in vivo of cell death in cerebral stroke. DDC may potentially assist in addressing the current "neuroimaging/neurohistology gap", for molecular assessment of the extent of stroke-related cell death.
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PMID:Novel molecular imaging of cell death in experimental cerebral stroke. 1732 73


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