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

Increased plasma lipoprotein (a) (Lp(a)) levels are strongly associated with premature cardiovascular disease and stroke. Recently we, as well as other groups, found that apolipoprotein (a) (apo(a)) fragments appear in the urine of healthy individuals, and that renal transplant patients with impaired renal function excrete fewer apo(a) fragments into their urine compared with controls. As the excretion mode of apo(a) is presently unknown, we determined plasma Lp(a) levels and urinary apo(a) excretion in relation to kidney function in 58 proteinuric patients and 58 healthy controls. For the first time, urinary apo(a) excretion was related to apo(a) isoforms. Plasma Lp(a) values were higher in the proteinuric patients compared with the controls, independent of their renal function. The patients with low-molecular-weight apo(a) isoforms had higher Lp(a) plasma levels, whereas the patients with high-molecular-weight apo(a) isoforms had lower Lp(a) plasma levels. Urinary apo(a) showed a very similar pattern to that of plasma Lp(a), being significantly higher in patients with low-molecular-weight isoforms as compared with patients with high-molecular-weight isoforms. Urinary apo(a) excretion was significantly decreased in the patient group when compared with healthy controls. There was a close correlation (P < 0.001) between the plasma Lp(a) and urinary apo(a) excretion in both the patient group and the control group. Urinary apo(a) excretion did not correlate with protein excretion, creatinine clearance or plasma creatinine levels. We conclude that urinary apo(a) excretion correlates with plasma Lp(a) and Lp(a) isoforms, and that proteinuric patients excrete significantly less apo(a) into their urine than healthy controls, a factor that might contribute to increased plasma Lp(a) levels in these patients.
 ...
PMID:Urinary apolipoprotein (a) excretion in patients with proteinuria. 981 37

Several factors that increase the likelihood of developing Alzheimer's disease (AD) have already been identified. A correct evaluation of these may contribute to a better understanding of the etiology of the disease. The risk of developing AD definitely increases with (a) age, (b) head injuries, (c) family history of AD or Down syndrome, (d) sex (higher prevalence of AD in women), (e) vascular disease, (f) exposure to environmental toxins, (g) infectious processes, or (h) changes in immune function, and recent advances in molecular genetics have suggested that genetic predisposition (i) can be considered one of the most important risk factors in the development of AD. A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (ApoE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of ApoE. A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with amyloid plaques. It has become evident that a dysregulation of cytokine release appears within lesions of many types of brain disorders including infection, trauma, stroke, and neurodegenerative diseases. Many studies have shown that microglia secrete both cytokines and cytotoxins and since reactive microglia appears in nearly every type of brain damage, it is likely that their secreted products ultimately help to determine the rate of damaged brain tissue. In this study, in vitro cell cultures were established to investigate the effect of different concentrations of human sera (2.5% and 10%) with specific ApoE genotypes from Alzheimer's and non-Alzheimer's subjects on ameboid and flat microglial cells obtained from neonatal rat hippocampi. Results show that a modulation in the proliferation and activation of microglial cells was obtained and that AD sera, mainly in the ApoE 3/4 and 4/4 genotype contain factor(s) which are able to induce morphological changes, as measured by an increase in the ameboid cell type. In addition, major histocompatibility complex (MHC) class II antigen expression, as measured by flow cytometric analysis, and interleukin-1beta (IL-1beta) release as measured by enzyme linked immunoadsorbent assay (ELISA), in comparison with control groups and lipopolysaccharide (LPS)-treated cells, clearly demonstrate a direct effect of ApoE 3/4 and 4/4 and/or an indirect effect mediated by the release of IL-1beta on microglia activation. These results strongly suggest that primary in vitro microglial cell cultures can be used as a screening model to test human sera as well as the effect of new potential drugs aimed at down-regulating microglia activation.
 ...
PMID:Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes. 982 64

The purpose of this study was to investigate the role of genetic polymorphisms associated with venous and arterial thrombosis in patients with retinal vein occlusion (RVO). One-hundred and two consecutive patients with RVO were examined for factor V G1691A and factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and apolipoprotein E4 by amplification of specific DNA fragments and restriction analysis. The risks exerted by these polymorphisms and by the conventional risk factors of RVO were evaluated by comparing their frequencies among patients and controls and by estimating the respective odds ratios. We found that the prevalences of the factor V G1691A, factor II G20210A, and apolipoprotein E4 polymorphisms were similar in the study and control groups. Logistic regression analysis involving the parameters for which significant differences were detected disclosed an odds ratio of 1.9 for MTHFR C677T homozygosity (95% confidence interval 0.95-3.81), an odds ratio of 2.12 for hypertension (95% confidence interval 1.16-3.73) and an odds ratio of 3.25 for a family history of stroke (95% confidence interval 1.07-9.51). Our data suggests that homozygosity for the MTHFR C677T polymorphism is a risk factor of RVO in addition to arterial hypertension and a family history of stroke.
 ...
PMID:Analysis of genetic polymorphisms related to thrombosis and other risk factors in patients with retinal vein occlusion. 986 10

This paper reviews aspects of existing knowledge and recent concepts related to the development of vascular dementia which, after Alzheimer's disease, is the most frequent type of dementia. The disorder may result from cerebrovascular disorders, including multi-infarct dementia due to thromboembolic disease, other less common vasculopathies and ischemic brain damage secondary to systemic hypotension. Characteristic clinical features are stepwise cognitive deterioration resulting from repeated strokes and the presence of focal signs and symptoms. The clinical distinction between Alzheimer's disease and vascular dementia may be difficult and strict criteria (NINDS/ AIREN) have recently been adopted as standard guidelines for research studies. Vascular dementia and Alzheimer's disease can co-exist, so-called "mixed dementia", and the presence of cerebrovascular disease may worsen Alzheimer dementia. Indeed, there is often a vascular component in the pathogenesis of dementia. The pathogenesis of vascular dementia is complex. Post-stroke patients are at increased risk; some predisposing or risk factors are the volume, number and site (whether strategic or not) of cerebral injuries, distal field vascular injury with reduced cerebral blood flow, white matter ischemia due to small vessel disease, the co-existence of vascular disease and Alzheimer's dementia, and the presence of cognitive decline prior to stroke. There is increasing evidence of a complex relationship between vascular dementia and Alzheimer's disease. When post-stroke dementia is progressive this may reflect associated Alzheimer's disease either unrecognized or asymptomatic prior to the stroke. The apolipoprotein E4 genotype is a risk factor for ischemic stroke, vascular dementia and Alzheimer dementia. Although dementia is usually irreversible, it is now accepted that cognitive impairment may be delayed, stabilized or sometimes reversed. The treatment of vascular dementia consists of two approaches: preventive measures, including attempts to control risk factors for stroke and the use of antiplatelet agents and/or surgery, and the treatment of cognitive symptoms. Nootropic and vasodilator agents have been reported to improve cognitive impairment from various causes. Ongoing research is attempting to show their specific benefit in vascular dementia.
 ...
PMID:From neuronal and vascular impairment to dementia. 1033 4

Apolipoprotein E fulfills fundamental functions in lipid transport and neural tissue repair after injury.(6,8) Its three most common isoforms (E2, E3, and E4) are critical determinants of diverse human diseases, including major cardiovascular and neurodegenerative disorders.(8,14) Apolipoprotein E4 is associated with an increased risk for Alzheimer's disease(3,5) and poor clinical outcome after head injury or stroke.(11,16) The precise role of apolipoprotein E4 in these conditions remains unknown. To characterize the effects of human apolipoprotein E isoforms in vivo, we analysed transgenic Apoe knockout mice that express apolipoprotein E3 or E4 or both in the brain. Hemizygous and homozygous apolipoprotein E3 mice were protected against age-related and excitotoxin-induced neurodegeneration, whereas apolipoprotein E4 mice were not. Apolipoprotein E3/E4 bigenic mice were as susceptible to neurodegeneration as apolipoprotein E4 singly-transgenic mice. At eight months of age neurodegeneration was more severe in homozygous than in hemizygous apolipoprotein E4 mice consistent with a dose effect. Thus, apolipoprotein E4 is not only less neuroprotective than apolipoprotein E3 but also acts as a dominant negative factor that interferes with the beneficial function of apolipoprotein E3. The inhibition of this apolipoprotein E4 activity may be critical for the prevention and treatment of neurodegeneration in APOE varepsilon4 carriers.
 ...
PMID:Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. 1079 51

Patients with human immunodeficiency virus show increased atheroembolism and premature arterial events (stroke, myocardial infarction), but no increased venous thromboembolism. This paper describes an association of elevated lipoprotein(a), a decreased prostaglandin I(2)(PGI(2)) synthesis stimulating plasma factor, diminished PGI(2)-stability in plasma and decreased high-density lipoprotein-cholesterol and apolipoprotein A. It is unclear to what extent these biochemical findings represent an acute phase reaction only or a disturbance in the prostaglandin system. Definitely, they are resulting in severe hemostatic imbalance decreasing local PGI(2)-availability with a dramatic reduction in the cytoprotective capacity favouring the onset of premature arterial events seen in some of the patients.
 ...
PMID:Association of lipoprotein(a), prostaglandin I(2)--synthesis stimulating plasma factor, biological half-life of prostaglandin I(2)and high-density lipoproteins in HIV-1 infection of different stages. 1109 Feb 58

The human renin gene (REN) is a good candidate in studies aimed at unravelling the genetic basis of essential hypertension and stroke. We previously established that both a BglI and an MboI dimorphisms (located respectively in the first and ninth introns of the REN gene) were associated with essential hypertension in a population of hyperlipidaemic US subjects. In this association (retrospective case-control) study, we investigated the haplotype distribution of alleles defined by the combination of REN BglI and MboI dimorphic sites in 329 hyperlipidaemic US Caucasian subjects referred to UCSF Medical Center (140 hypertensives, 141 normotensives, and 48 hypertensive patients who had suffered a stroke). A statistically significant association was found between alleles determined by both (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) haplotypes and clinical diagnosis of EHT (combined odds ratios, OR = 3.35, corrected P < 10(-7)). Haplotypes (-,+) and (+,+) were also found to be associated with clinical diagnosis of stroke (OR = 4.31, P < 10(-7)). These associations do not occur through the effects of classical risk factors related to lipid, lipoprotein and apolipoprotein levels. We conclude that variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with REN (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) alleles could play a role in contributing to increased individual's genetic susceptibility to EHT and to stroke. Journal of Human Hypertension(2001) 15, 49-55
 ...
PMID:Haplotypes of the human renin gene associated with essential hypertension and stroke. 1122 2

We used stored plasma samples from 409 patients in the National Institute of Neurological Diseases and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Trial to examine the relationship between an apolipoprotein (Apo) E2 or an Apo E4 phenotype and a favorable outcome 3 months after stroke, the risk of intracerebral hemorrhage, and the response to intravenous t-PA therapy. For the 27 patients with an Apo E2 phenotype who were treated with t-PA, the odds ratio (OR) of a favorable outcome at 3 months was 6.4 [95% confidence interval (CI) 2.7-15.3%] compared to the 161 patients without an Apo E2 phenotype who were treated with placebo. The 190 patients treated with t-PA who did not have an Apo E2 phenotype also had a greater, though less pronounced, likelihood of a favorable outcome (OR 2.0, 95% CI 1.2-3.2%) than patients without an Apo E2 phenotype treated with placebo. For the 31 patients with an Apo E2 phenotype treated with placebo, the OR of a favorable 3 month outcome was 0.8 (95% CI 0.4-1.7%) compared to the 161 patients without an Apo E2 phenotype treated with placebo. This interaction between treatment and Apo E2 status persisted after adjustment for baseline variables previously associated with 3 month outcome, for differences in the baseline variables in the two treatment groups and in the Apo E2-positive and -negative groups, and for a previously reported time-to-treatment x treatment interaction (p = 0.03). Apo E4 phenotype, present in 111 (27%) of the 409 patients, was not related to a favorable 3 month outcome, response to t-PA, 3 month mortality, or risk of intracerebral hemorrhage. We conclude that the efficacy of intravenous t-PA in patients with acute ischemic stroke may be enhanced in patients who have an Apo E2 phenotype, whereas the Apo E2 phenotype alone is not associated with a detectable benefit on stroke outcome at 3 months in patients not given t-PA. In contrast to prior studies of head injury and stroke, we could not detect a relationship between Apo E4 phenotype and clinical outcome.
 ...
PMID:Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke. 1140 25

Elevated plasma levels of lipoprotein (a) [Lp(a)] constitutes an independent risk factor for coronary heart disease, stroke, and restenosis. Over the past years, our understanding of the genetics, metabolism and pathophysiology of Lp(a) have increased considerably. However, the precise mechanism(s) by which this atherogenic lipoprotein mediates the development of atherosclerosis remains unclear. This is partly due to the lack of appropriate animal models since apolipoprotein (a) [apo(a)], a distinct component of Lp(a) is found only in primates and humans. Development of transgenic mice expressing human apo(a) has provided an alternative means to investigate many aspects of Lp(a). However, human apo(a) in transgenic mice can not bind to murine apoB to form Lp(a) particles. In this aspect, we generated transgenic rabbits expressing human apo(a). In the plasma of transgenic rabbits, unlike the plasma of transgenic mice, about 80% of the apo(a) was associated with rabbit apo B and was contained in the fractions with density 1.02-1.10 g/ml, indicating the formation of Lp(a). Our study suggests that transgenic rabbits expressing human apo(a) exhibit efficient assembly of Lp(a) and can be used as an animal model for the study of human Lp(a).
 ...
PMID:Transgenic rabbits expressing human apolipoprotein (a). 1142 47

Stroke places a tremendous burden on health resources throughout the world. Improved detection and modification of risk factors could reduce the impact of this disease. Important non-modifiable risk factors for ischemic stroke include age, gender, ethnicity, and heredity. Modifiable risk factors include hypertension, cardiovascular disease, diabetes, hyperlipidemia, asymptomatic carotid stenosis, cigarette smoking, and alcohol abuse. Data from the Northern Manhattan Stroke Study provide new insights into these stroke risk factors. In this study, African-Americans and Hispanics had a greater incidence of stroke, with almost a twofold increase compared with Caucasians. The protective effect of physical activity and moderate alcohol consumption was confirmed and further established as modifiable risk factors. The independent effects of lipids, apolipoproteins, and lipoprotein were also clarified. High-density lipoprotein was shown to be protective against ischemic stroke (particularly atherosclerotic stroke subtypes). Conversely, lipoprotein-a increased the risk for stroke. The ratio of apolipoprotein b to apolipoprotein a-1 was shown to be associated with carotid atheroma. In addition, newer risk factors, including homocysteine and chronic infection (Chlamydia pneumoniae and periodontal disease), are being studied as predictors of ischemic stroke. With these recent advances in the understanding of risk factors, the ability to detect or modify the risk for ischemic stroke should lead to a substantial reduction in the number of people killed or disabled by stroke each year.
 ...
PMID:Newer risk factors for stroke. 1155 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>