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)

In this study, the authors examined relations between coronary and carotid atherosclerosis and between coronary atherosclerosis and silent cerebral infarction. They ascertained the risk factors for carotid atherosclerosis and silent cerebral infarction complicating coronary heart disease (CHD) in 77 Japanese subjects. As coronary atherosclerosis progressed, the carotid ultrasonographic score and the brain computed tomographic score increased. Multivariate analyses showed that the significant and independent risk factors for carotid atherosclerosis in patients with CHD were age (p < 0.01) and apolipoprotein (apo) B (p < 0.05) and the factors for silent cerebral infarction were age (p < 0.05) and hypertension (p < 0.05). Their study confirms a positive relation between coronary atherosclerosis and carotid atherosclerosis and between coronary atherosclerosis and silent cerebral infarction in patients with CHD. Their data suggest that carotid atherosclerosis should be looked for in patients with CHD who are old and have a high value of apo B, and silent cerebral infarction should be looked for in those who are old and have hypertension, to prevent complicating symptomatic cerebral vascular disease (CVD). If severe carotid atherosclerosis or silent cerebral infarction are detected, antithrombotic medication should be given.
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PMID:Risk factors for carotid atherosclerosis and silent cerebral infarction in patients with coronary heart disease. 850 8

Dyslipidemia is an important risk factor for atherosclerotic vascular disease. Serum lipoprotein (a) [Lp(a)] has been implicated as an independent atherogenic risk factor. We measured serum (Lp(a) levels in our patients and studied its correlations with other lipoproteins and clinical parameters. All stable patients on continuous ambulatory peritoneal dialysis (CAPD) for more than one month were enrolled in the study. Fasting serum Lp(a), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, apolipoprotein-A and apolipoprotein-B levels were measured on entering the CAPD program and at 3 monthly intervals. One hundred and nine patients (M/F: 65/44, mean age +/- SD: 59.5 +/- 12.0 years) were studied. Fifty-two patients had diabetes mellitus. Age- and sex-matched normals were used as controls. Serum Lp(a) levels were raised in 54.5% of CAPD patients compared to 18.6% of controls (p < 0.01). There was no significant change in Lp(a) levels over time. Serum Lp(a) levels showed positive and negative correlations with LDL-cholesterol and triglycerides, respectively, but not with age, sex, diabetic status, and serum total cholesterol and albumin levels. Thirty-six of 54 (66.7%) patients with serum Lp(a) levels greater than 30 mg/dL had either coronary, cerebral, and/or peripheral vascular disease compared to 30/55 (54.5%) of patients with serum Lp(a) levels less than 30 mg/dL (p = NS). In conclusion, serum Lp(a) levels were raised in a significant proportion of CAPD patients, but there was no significant association with vascular disease.
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PMID:Lipoprotein (a) levels and clinical correlations in CAPD patients. 853 86

The goal of this study was to compare the structural and biological characteristics of apolipoprotein (apo) B-100-containing particle subfractions isolated from poorly controlled diabetic patients with insulin-dependent diabetes (IDDM), and healthy controls matched for sex, age and body mass index (BMI). Different apo B-containing particles were isolated by sequential immunochromatography and were free of apo A-I, apo A-II, apo A-IV and apo(a). Particles lipoprotein (Lp) B/C-III contained apo B and apo C-III. They were free of apo E. Particles Lp B/E contained apo B and apo E. They were free of apo C-III. Particles Lp B were devoided of apo C-III and apo E. All these particles could contain other known apolipoproteins not cited here, as for example apo C-II and/or apo C-I. The plasma levels of cholesterol, triglycerides, phospholipids, apo A-I, B-100, C-III, E, total Lp B/C-III, total Lp B/E were not different between patients and controls. The physico-chemical properties of Lp B/C-III and Lp B/E were similar in both groups. Only Lp B from patients exhibited some changes, an increase in the size and a decrease in the cholesterol and cholesteryl ester levels. The conformational properties of the lipoproteins were studied through their immunoreactivity against four different anti-apo B-100 monoclonal antibodies (MAb) for which sequential epitopes have been located on the protein, and one MAb for which the epitope is conformationally expressed. Again, minor changes were observed between patients and controls, and only a slight decrease in the immunoreactivity of the epitope encompassing amino-acid residues 405 to 539 of Lp B and of the conformationally expressed epitope of Lp B/C-III were found in patients. Nevertheless, whatever these conformational and/or physico-chemical modifications may be, they were not sufficient to induce functional alterations in the binding of the particles from the patients to the LDL-receptor of HeLa cells. This study shows that IDDM is not associated with any significant abnormalities in the apo-containing lipoprotein particles. The excessive occurrence of coronary heart disease (CHD) and other atherosclerotic vascular disease in patients with IDDM must have other causes.
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PMID:Apo B-containing lipoprotein particles in poorly controlled insulin-dependent diabetes. 864 62

Significant developments in our understanding of the pathophysiology of Alzheimer's disease have been obtained in the recent years. Diagnostic criteria, based on clinical data, have been proposed and have been validated by clinico-pathological correlations. Some neuroimaging techniques and laboratory tests (e.g. dosage in the cerebrospinal fluid) are promising diagnostic avenues. Genetic mutations associated with familial cases of the disease have been identified and the involved genes localized on chromosome 1, 14 or 21. The apolipoprotein E genotype has been discovered to affect the risk of developing the disease, i.e. homozygotes for the apolipoprotein E4 allele are much more prone to develop Alzheimer's disease The definitive diagnosis of the disease still relies on the demonstration of characteristic neuropathological lesions, i.e. neurofibrillary tangles and senile plaques, whose numbers are correlated with the severity of the dementia. Other lesions include neuronal and synaptic loss, amyloid angiopathy, and severe decrease in the level of cortical acetylcholine. Neurofibrillary tangles have been found to be composed of the microtubule-associated protein tau, in highly phosphorylated state. The accumulation of these phosphorylated tau proteins is thought to be associated to disturbances of intracellular transport of molecules and organelles in affected neurones, leading to cell dysfunction and death. An inbalance in the activities of selected protein kinases and phosphatases is also thought to generate these highly phosphorylated tau species. The major component of senile plaques is the A4/beta amyloid peptide, generated by proteolysis of the amyloid peptide precursor, a transmembrane protein. When aggregated into amyloid fibrils, the A4/beta amyloid peptide is thought to be neurotoxic. An abnormal metabolism of the amyloid peptide precursor is often considered as a central physiopathological mechanism of the disease. Although many pharmacological treatments of the disease have been investigated, they have not yet led to sustained and major clinical improvements.
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PMID:The neurobiology of Alzheimer's disease. 869 72

A significant component of the aging process is genetically determined. Numerous theories of aging exist, many of which postulate the existence of "longevity genes." Recent advances in molecular biological and other techniques have allowed a significantly greater understanding of aging and age-related disease. This will be illustrated by four genetic and sporadic diseases: Alzheimer's disease (AD) and related disorders, transthyretin dementia, cerebral amyloid angiopathy-Icelandic type and scrapie related diseases. Alzheimer's disease (AD), the most common of this group, is the leading cause of dementia in Western countries. Recent genetic and biochemical studies have shown the involvement of at least four genes in the pathogenesis of AD. In early-onset familial AD mutations in the beta PP, S182 (presenilin 1) and STM2 (presenilin 2 or E5-1) genes have been found, while in the more common late-onset AD the presence of the apolipoprotein E4 isotype is a major risk factor. Genetic studies have also helped to elucidate the etiology of rarer cerebral amyloidoses such as the recently described Hungarian amyloidosis that is characterized by meningocerebrovascular amyloid deposition, with resultant dementia. This disease is linked to a mutation in the transthyretin gene. It is hoped that in the near future this increase in knowledge will allow the development of therapeutic approaches to slow the aging process.
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PMID:Molecular biology of brain aging and neurodegenerative disorders. 878 86

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.
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PMID:Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes. 982 64

Pathological correlations were sought between cerebral amyloid angiopathy (CAA) and other classical neurodegenerative changes in 101 consecutive cases of autopsy-confirmed Alzheimer disease (AD). Some degree of CAA was found in at least one area of the brain in 81% of the cases; severe CAA was found in at least one brain region in 29% of the cases. In a subset of 42 cases for which genomic DNA was available, greater severity of CAA was associated more with cases that were homozygous for apolipoprotein epsilon4 than in cases with only one or no epsilon4 alleles (Fisher's exact test, p = 0.005). In all brain regions, severity of CAA was inversely correlated with numbers of neurons. This correlation was statistically significant in the temporal lobe (r = -0.29,p = 0.004) and the frontal lobe (r = -0.22, p = 0.02). Our findings suggest that two factors may modify the severity of AD pathology: Apolipoprotein E4 may accentuate the vascular deposition of beta-amyloid, and severe CAA may accelerate neuronal loss.
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PMID:Cerebral amyloid angiopathy in Alzheimer disease is associated with apolipoprotein E4 and cortical neuron loss. 1019 36

Coronary artery disease is a leading cause of death in France. Some of its risk factors are well identified such as age, smoking, high blood pressure and dyslipidemia, but some others such as lipoprotein (a) (Lp(a)) are still under investigation. Lp(a) is an LDL-like particle to which is linked an apolipoprotein (a). The latter shows a high sequence homology with plasminogen that gives Lp(a) thrombogenic properties in addition to its atherogenic capacity. Many epidemiological studies have shown that a high plasma level of Lp(a) is a risk factor for coronary, cerebral and peripheral atherosclerosis. Out of thirteen prospective studies, ten have confirmed this result. The negative results from the three remaining studies were probably due to either the inadequate storage of the samples or the preventive drug treatment given to the patients during the studies and to the lack of standardization of Lp(a) assays. More over it has been shown that beside high plasma Lp(a) level, the presence of a low molecular weight Apo(a) isoform is also related to a higher incidence of coronary artery disease. This review of the literature clearly demonstrates the relationship between Lp(a) and atherosclerosis, and the need to measure Lp(a) in order to better evaluate the risk of atherosclerotic vascular disease especially in patients with a hyper LDLemia an early cardio- or cerebrovascular disease or a family history of atherosclerosis. Management of patients with high Lp(a) concentrations should be directed at minimizing all other risk factors for atherosclerotic disease.
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PMID:[Lipoprotein(a): risk factor for atherosclerotic vascular disease important to take into account in practice]. 1021 Jul 42

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.
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PMID:From neuronal and vascular impairment to dementia. 1033 4

It is well recognized that blood lipoprotein A [Lp(a)] levels constitute an important risk factor for atherosclerotic vascular disease. In some populations, mainly Caucasian, Lp(a) levels and coronary heart disease (CHD) risk are determined by the pattern of apolipoprotein a [apo(a)] polymorphism. It is currently unclear if these observations apply to other populations and ethnic groups. The aim of the current study is to determine to what extent known apo(a) polymorphisms associate with development of CHD in a Kuwaiti Arab population. Serum Lp(a) levels were measured by enzyme-linked immunosorbent assay and apo(a) isoforms determined by a high-resolution sodium dodecyl sulphate/agarose gel electrophoresis with immunoblotting in two groups of Kuwaiti subjects: healthy controls (n = 140) and subjects with CHD (n = 140). Blood lipids and anthropometric parameters were also determined in these subjects by standard methods. Serum Lp(a) levels were greater in those with CHD than in those in the healthy group (P < 0.001). There was no consistent trend in the pattern of serum Lp(a) levels found with specific apo(a) isoforms in either group of subjects. There was, therefore, no simple relationship between the isoform pattern (and number of kringle-IV repeats) and serum Lp(a) concentration, unlike in certain other populations. Additionally, almost identical proportions of subjects in either group had single-banded (homozygous, approximately 70%), double-banded (heterozygous, approximately 23%) and no-band (null, approximately 7%) phenotypes. The distribution of the five identified isoforms (F, S1, S2, S3 and S4) also was almost identical for both groups of subjects, whether homozygous or heterozygous, and whether classified into fast-moving (F, S1 and S2) or slow-moving (S3 and S4) isoforms. We conclude that the frequency and pattern of distribution of apo(a) phenotypes did not differ significantly between healthy control Kuwaiti Arab subjects and those with CHD. It is thus unlikely that an individual's apo(a) phenotype can predict both serum Lp(a) level and risk for CHD, irrespective of race and/or ethnic grouping.
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PMID:Apo(a) isoforms do not predict risk for coronary heart disease in a Gulf Arab population. 1081 52


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