Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variation at the apolipoprotein E (apo E) gene locus affects cholesterol concentrations, the risk for atherosclerosis and Alzheimer disease (AD), and is associated with longevity in Caucasians. We have determined apo E gene frequencies and effects on cholesterol levels in Khoi San (Bushmen) from South Africa. The frequency of the apo epsilon 4 allele (0.37), which confers dose-dependent susceptibility to atherosclerosis and AD in Caucasians, was twice as high, and apo E4 homozygotes were 3-5 fold more frequent in the Khoi San (approximately 10%) compared with Caucasians (2%-3%). No significant effect of apo E variation on cholesterol concentration was noted in this non-Westernized population with low plasma cholesterol (mean cholesterol 149 mg/dl). This suggests that Bushmen carry a heavy genetic burden for these late-onset disorders if exposed to a Western lifestyle.
 ...
PMID:High frequency of the apo epsilon 4 allele in Khoi San from South Africa. 781 25

We report a patient with long-standing systemic hypertension who developed progressive generalized chorea and dementia beginning at 70 years of age with no family history or other features to suggest Huntington's disease. At postmortem examination, congophilic angiopathy and atherosclerosis causing neostriatal neuronal loss and gliosis were found, in addition to plaques and neurofibrillary tangles in the cortex. This case is a rare demonstration of a vascular pathology causing late onset generalized chorea in association with dementia due to Alzheimer's-type cortical changes.
 ...
PMID:Vascular chorea: case report with pathology. 796 13

Apolipoprotein E (apo E) is a polymorphic glycoprotein that plays an essential part in the binding to receptors for the uptake of chylomicrons and VLDL remnants and of LDL. The three major isoforms are E3 (Cys112/Arg158), E4 (Arg112/Arg158) and E2 (Cys112/Cys158). The apo E genetic variation has a great impact. In most of type III familial hyperlipoproteinemias (HLP), E2 is implicated at the homozygote status. In other cases, rare alleles are directly responsible for dominant type III HLP. Apo E polymorphism is an essential determinant in the interindividual variations of lipids in healthy subjects in various populations. Its influence can be significant on the efficacy of nutritional or therapeutic interventions. The allele epsilon 4 appears to be associated with an increased risk of premature atherosclerosis. Recently, epsilon 4 was demonstrated to be associated with an early Alzheimer's disease onset. Apo E polymorphism contributes to the lipid disorders in diabetes and obesity. The analysis of apo E polymorphism can be carried out with two conceptually different approaches. The first one is based on the separation of plasma isoforms of the protein by isoelectric focusing or bidimensional electrophoresis. The other one consists in the application of molecular biology techniques (PCR and endonuclease restriction profiles) for a detection of the common alleles and of several rare alleles, avoiding the possible errors of the phenotyping technique of the apo E protein. The application of genetic engineering allows a better understanding of the role played by apo E towards its receptors and in other molecular interactions which are not well known up to now.
 ...
PMID:[Pathology of the human apolipoprotein E gene]. 807 81

Primary defects in mitochondrial function are implicated in over 100 diseases, and the list continues to grow. Yet the first mitochondrial defect--a myopathy--was demonstrated only 35 years ago. The field's dramatic expansion reflects growth of knowledge in three areas: (i) characterization of mitochondrial structure and function, (ii) elucidation of the steps involved in mitochondrial biosynthesis, and (iii) discovery of specific mitochondrial DNA. Many mitochondrial diseases are accompanied by mutations in this DNA. Inheritance is by maternal transmission. The metabolic defects encompass the electron transport complexes, intermediates of the tricarboxylic acid cycle, and substrate transport. The clinical manifestations are protean, most often involving skeletal muscle and the central nervous system. In addition to being a primary cause of disease, mitochondrial DNA mutations and impaired oxidation have now been found to occur as secondary phenomena in aging as well as in age-related degenerative diseases such as Parkinson, Alzheimer, and Huntington diseases, amyotrophic lateral sclerosis and cardiomyopathies, atherosclerosis, and diabetes mellitus. Manifestations of both the primary and secondary mitochondrial diseases are thought to result from the production of oxygen free radicals. With increased understanding of the mechanisms underlying the mitochondrial dysfunctions has come the beginnings of therapeutic strategies, based mostly on the administration of antioxidants, replacement of cofactors, and provision of nutrients. At the present accelerating pace of development of what may be called mitochondrial medicine, much more is likely to be achieved within the next few years.
 ...
PMID:The development of mitochondrial medicine. 809 Jul 15

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. Our results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.
 ...
PMID:Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23. 812 15

A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrhythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriolosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT.
 ...
PMID:[A clinicopathological study of senile dementia of Alzheimer's type (SDAT) and white matter lesions of Binswanger's type]. 820 74

Injury of plant cells as well as mammalian cells is connected with the activation of 'dormant' lipoxygenases. In the presence of oxygen, these enzymes are activated and enabled to catalyze the formation of hydroperoxides of linoleic and other polyunsaturated fatty acids. Reactivity of dormant lipoxygenases seems to be dependent on the carbon number between the alkyl end and the double bond situated next to this end in an unsaturated acid. In contrast to these dormant lipoxygenases there exists a second group of lipoxygenases, which are active in plant cells all the time, independent of an injury. They react mainly with acids possessing two homoconjugated double bonds within a distance of seven CH2 groups from the carboxylic end. Thus, they 'count' from the reverse end of the molecule. These lipoxygenases produce F-acids. They are converted, when plant cells are injured by hydroperoxides produced from unsaturated acids, into dioxoenoic acid intermediates which probably are used for defense. In mammalian tissues, lipoxygenases produce in the case of cell injury plasmalogen epoxides. These are analogous to dioxoenoic acids' highly reactive intermediates (in a chemical sense) which react immediately with nucleophiles. Such transformation of plasmalogens may be responsible for the development of chronic diseases, e.g., atherosclerosis, Alzheimer's disease and also for aging.
 ...
PMID:Review: on the chemistry of oxidative stress. 821 2

General autopsy findings, brain weight and brain pathology were studied in 98 men and five women who had been exposed occupationally to organic solvents over several years and assessed by the Danish National Board of Industrial Injuries for chronic toxic encephalopathy. The findings were compared with a forensic control material and a hospital control material. As in the general population, the most common causes of death among the exposed workers were heart failure and other vascular diseases. Due to the composition of the material (forensic cases), the number of suicides and violent deaths was high. Atherosclerosis was the most common CNS finding, but in comparison with the two control materials, no increase in the frequency of atherosclerosis or of Alzheimer's disease was found. Brain weights of the exposed workers corresponded closely to brain weights in the control materials, after correction for body height, body weight and age. Chronic alcoholism was correlated with slightly reduced brain weight.
 ...
PMID:Brain autopsy in organic solvent syndrome. 833 41

Each cell is functionally restricted by differentiation, which determines its complement of active and inactive genes. Various diseases then become manifest in each cell, depending on these specific gene combinations. Neoplasia, for example, is due to a multistep series of genetic mutations. It is common in continuous replicators such as bronchial epithelium, colon, and marrow but rare in intermittent replicators such as endothelial and smooth muscle cells. In contrast, these latter cell types are centrally involved in degenerative phenomena such as atherosclerosis. However, in both continuous and intermittent replicators, reduction of gratuitous cell turnover will be of great benefit. The nonreplicating adult neuron almost never undergoes tumorigenesis compared with glial cells but gives rise to a variety of age-related degenerative diseases such as Alzheimer's or Parkinson's disease. In the nonreplicating neuron, therefore, it is imperative that we promote strategies to preserve cell viability by minimizing oxidative damage. Natural antioxidants such as vitamin C and E and beta carotene, as well as an optimal caloric and protein intake, should be cornerstones of treatment and prevention for the aging patient. A place for pharmacologic intervention is also likely soon. Current research should soon identify the precise mechanisms responsible for programmed cellular senescence and oxidative cellular damage so as to illuminate additional means of rational treatment, and perhaps more importantly, prevention.
 ...
PMID:The biology of aging: looking to defuse the genetic time bomb. 836 65

CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko-araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease.
 ...
PMID:Correlations of leuko-araiosis with cerebral atrophy and perfusion in elderly normal subjects and demented patients. 843 7


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