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

Apolipoprotein E (apoE) is one of several lipoprotein transfer genes. A primary function of this protein is the mediation of receptor-mediated lipoprotein removal from the blood. Several studies have demonstrated that genetic variation at the apoE locus is associated with an increased risk of developing atherosclerosis, and recent studies implicate this same genetic variation in determining susceptibility to Alzheimer's disease. An apoE-deficient mouse has been created to further understand the role of apoE in these areas. This review briefly discussed the biological and clinical importance of this protein and describes the early experiments performed in the apoE-deficient mouse.
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PMID:Apolipoprotein E and the apolipoprotein E-deficient mouse. 852 31

Hyperlipidemia is one of the risk factors for coronary atherosclerosis and the establishment of its simple etiological diagnosis is crucial. Hyperlipidemia can be classified into primary and secondary hyperlipidemia. Primary hyperlipidemia includes familial lipoprotein lipase (LPL) deficiency, familial hypercholesterolemia (FH), familial type III hyperlipidemia, and familial combined hyperlipidemia. Many genetic mutations have been identified in patients with familial LPL deficiency and FH. An ELISA kit has been established to determine LPL mass levels, using monoclonal antibodies against LPL. FH is a deficiency of LDL receptor and is characterized by marked hypercholesterolemia and Achilles tendon xanthomas. It can be diagnosed by an LDL receptor assay, using 125I-LDL in skin fibroblasts. However, the diagnosis can be made easily by measuring the uptake of DiI-LDL by peripheral lymphocytes. Familial type III hyperlipidemia is a genetic disorder characterized by the presence of a broad beta pattern in lipoprotein electrophoresis and is based upon the abnormality of apo E isoform (apo E2/2). Apo E4 has been shown to be associated with late-onset Alzheimer's disease. Cholesteryl ester transfer protein (CETP) deficiency is characterized by a marked hyperalphalipoproteinemia and various abnormalities in the size and composition of LDL and HDL. Two common mutations in the CETP deficiency have been identified; an intron 14 splicing defect and D442: G missense mutation. These mutations account for at least one half of hyper-HDL-cholesterolemia in the Japanese. We have recently identified an area (Omagari City, Akita) where the frequency of heterozygotes for the intron 14 splicing defect is approximately 28% of the general population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Progress in the diagnosis of endocrine and metabolic disorders: hyperlipidemia]. 855 75

Technologic progress in two-dimensional polyacrylamide gel electrophoresis (2-D Page), in combination with immunoblotting, amino acid sequencing, and computer-assisted image analysis, allowed establishment of human body fluid and tissue "reference maps," which in turn enabled meaningful comparison of data from various clinical and research centers. Altered protein profiles have been observed in plasma/serum, cerebrospinal fluid, urine, and other body fluids in numerous systemic or localized pathologic entities. Human perilymph, obtained during ear surgery or post mortem, exhibits a protein profile differing from plasma in several ways. Most interesting are the extremely high levels of high density lipoprotein-associated proteins, a group of proteins thought to play a role in atherosclerosis, nerve damage/regeneration, chronic inflammation, and Alzheimer's disease, among others. A technique is described for collection and analysis of human perilymph, using a state-of-the-art standardized 2-D Page technique. It is expected that, as in other body fluids, disease-specific protein patterns will be identified. With the possible exception of presumed perilymphatic fistula, it is not envisioned that analysis of perilymph will be used for diagnostic purposes but rather as an aid for the elucidation of the mechanisms underlying inner ear disease, whether localized or as part of systemic alterations.
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PMID:High resolution two-dimensional electrophoresis: technique and potential applicability to the study of inner ear disease. 857 13

The macrophage scavenger receptor is a multifunctional receptor whose ligands include oxidized low density lipoprotein (LDL), as well as several other polyanionic macromolecules. Although the capacity of the receptor to bind modified LDL has implicated it in the process of atherosclerosis, its physiological role remains uncertain. We have examined human brain for expression of macrophage scavenger receptor as part of ongoing studies of lipoprotein receptors in the central nervous system. The receptor is expressed on microglia, but not on astrocytes, neurons, or vessel-associated structures. In Alzheimer disease, there is strong expression of the scavenger receptor in association with senile plaques.
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PMID:Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer's disease. 857 3

The paradox of aerobic life, or the 'Oxygen Paradox', is that higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. This 'dark side' of oxygen relates directly to the fact that each oxygen atom has one unpaired electron in its outer valence shell, and molecular oxygen has two unpaired electrons. Thus atomic oxygen is a free radical and molecular oxygen is a (free) bi-radical. Concerted tetravalent reduction of oxygen by the mitochondrial electron-transport chain, to produce water, is considered to be a relatively safe process; however, the univalent reduction of oxygen generates reactive intermediates. The reductive environment of the cellular milieu provides ample opportunities for oxygen to undergo unscheduled univalent reduction. Thus the superoxide anion radical, hydrogen peroxide and the extremely reactive hydroxyl radical are common products of life in an aerobic environment, and these agents appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate--or garner from their surroundings--a variety of water- and lipid-soluble antioxidant compounds. Additionally, a series of antioxidant enzymes, whose role is to intercept and inactivate reactive oxygen intermediates, is synthesized by all known aerobic organisms. Although extremely important, the antioxidant enzymes and compounds are not completely effective in preventing oxidative damage. To deal with the damage that does still occur, a series of damage removal/repair enzymes, for proteins, lipids and DNA, is synthesized. Finally, since oxidative stress levels may vary from time to time, organisms are able to adapt to such fluctuating stresses by inducing the synthesis of antioxidant enzymes and damage removal/repair enzymes. In a perfect world the story would end here; unfortunately, biology is seldom so precise. The reality appears to be that, despite the valiant antioxidant and repair mechanisms described above, oxidative damage remains an inescapable outcome of aerobic existence. In recent years oxidative stress has been implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. Some of these oxidation-linked diseases or disorders can be exacerbated, perhaps even initiated, by numerous environmental pro-oxidants and/or pro-oxidant drugs and foods. Alternatively, compounds found in certain foods may be able to significantly bolster biological resistance against oxidants. Currently, great interest centres on the possible protective value of a wide variety of plant-derived antioxidant compounds, particularly those from fruits and vegetables.
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PMID:Oxidative stress: the paradox of aerobic life. 866 Mar 87

Central nervous system has a low antioxidative capacity, which is formed mainly by ascorbic acid. Therefore the cerebral tissue is threatened by the increased formation of free radicals and their metabolites (ROS--reactive oxygen species). ROS are formed such as in reperfusion phase after ischemia and in catecholamine metabolism, in oxidative stress due to hyperglycaemia. Polyunsaturated fatty acids (PUFA) are peroxidased by ROS; proteins and DNK are damaged as well. Free radicals are involved in etiology and pathogenesis of many CNS diseases, such as neuritis, Alzheimer disease, Parkinson disease, Huntington disease, aging and atherosclerosis of the brain, epilepsy, etc. During the antioxidant therapy it is necessary to consider the types of ROS, their origin and their mode of action, whether to administer hydrophilic or lipophilic antioxidants, eventually chelate agents, etc. Hydrophylic antioxidants are acting very soon after the administration, whereas the lipophilic ones reach their target tissues with a great delay. Therefore it is better to apply them preferentially like a prevention, if possible. Enzymatic antioxidants (SOD, GSPHx and catalase and others) are usually acting only for a short time. The methods of estimation of free radicals attacks are discussed as well their possible pathophysiological effects.
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PMID:[Free radicals in the central nervous system]. 866 12

The presence of apolipoprotein E-epsilon4 (APOE-epsilon4) allele has been implicated as a risk factor for Alzheimer's disease (AD). We examined the frequencies of APOE-epsilon4 alleles in age-matched controls and subgroups of 190 AD subjects exhibited cerebral amyloid angiopathy (CAA) and other frequently associated lesions. CAA was evident in 96% of the AD subjects, which were divided into two groups, one bearing mild or no apparent CAA and the other with moderate to severe CAA. APOE-epsilon4 allele frequency (48%) in the latter advanced CAA group was six times higher than in those who exhibited mild CAA. In the advanced CAA subjects, the occurrence of an epsilon4 allele was increased by a factor of 17 (95% confidence interval, 7.56 to 38.9). This was despite the fact that neocortical amyloid-beta plaque densities in the two groups were similar and that all of the AD subjects had met the accepted neuropathological criteria. We also observed that the degree of CAA severity was greatest in the group of subjects with the epsilon4/epsilon4 genotype. The association between CAA and APOE-epsilon4 was further implicated in two non-AD subjects among neurological controls with severe CAA. These two subjects, both homozygous for the APOE-epsilon4 allele, were primarily diagnosed as having Creutzfeldt-Jakob disease and Pick's disease in the absence of significant neocortical amyloid deposition. Allele frequency comparisons between neurological control subjects with CAA and those without likewise accorded a strong relationship between the APOE-epsilon4 allele and the presence of CAA. More remarkably, the epsilon4 allele frequency was highly associated with AD subjects exhibiting lobar or intracerebral hemorrhage, all of whom had advanced CAA. We observed that 36% of the AD subjects had concomitant cerebrovascular pathology resulting from single infarcts, multiple microinfarcts, ischemic white matter lesions, or petechial hemorrhages. Although the difference in APOE genotype distribution between subjects with and without cerebrovascular lesions did not reach statistical significance, we did note that the frequency of the epsilon4 allele was significantly higher in subjects with such pathology as compared with those without. However, we found no evidence to suggest that the acquisition of an APOE-epsilon4 allele or one of the alleles, epsilon2 or epsilon3, was a factor in the occurrence of atherosclerosis localized in the basal surface arteries. Analyses of our sample also confirm that there was a lower frequency of the APOE-epsilon2 allele in AD subjects and that the frequency of the epsilon4 allele in AD subjects with concomitant diffuse Lewy body disease was intermediate between controls and AD subjects. Our results suggest that the APOE-epsilon4 allele is a significant factor in the development of CAA in AD and reveal the possibility that APOE is an independent factor in CAA and other vascular abnormalities associated with AD.
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PMID:Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. 866 92

Dehydroepiandrosterone (DHEA) is quantitatively the most abundant hormone in humans and mammals, with a wide variety of physiological effects, including major regulatory effects upon the immune system. Two of the most striking aspects of DHEA are a steady decline in DHEA with age and a significant deficiency in DHEA in patients with several major diseases, including cancer, atherosclerosis, and Alzheimer's disease. The hormone is secreted in a non-sulfated (DHEA) and sulfated form (DHEA-S). The two are apparently interchangeable, and it appears likely that its physiological effects are achieved by derivative molecules that have yet to be identified.
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PMID:A review of dehydroepiandrosterone (DHEA). 878 27

Advanced glycation end-products (AGEs) are formed by spontaneous chemical reactions between carbohydrates and tissue proteins. The accumulation of AGEs in long-lived proteins contributes to the age-related increase in brown colour, fluorescence and insolubilisation of lens crystallins and to the gradual crosslinking and decrease in elasticity of connective tissue collagens with age. These nonenzymatic reactions, known collectively as Maillard or browning reactions, are also implicated in the development of pathophysiology in age-related diseases such as diabetes mellitus, atherosclerosis, Alzheimer's disease, and in dialysis-related amyloidosis. Oxygen and oxidation reactions accelerates Maillard reactions in vitro, and the structurally characterised AGEs that accumulate in long-lived tissue proteins are in fact glycoxidation products, formed by sequential glycation and oxidation reactions. In addition to their immediate effects on protein structure and function, AGEs also induce oxidative stress, leading to inflammation and propagation of tissue damage. Thus, glycation of protein, formation of AGEs and resultant oxidative stress, which accelerate Maillard reactions, can initiate an autocatalytic cycle of deleterious reactions in tissues. Pharmacological inhibition of the Maillard reaction should improve the prognosis for a broad range of age-related diseases. The role of oxidative stress as a catalyst and the consequences of Maillard reaction damage in tissues suggests that antioxidant therapy may also retard the progression of age-related pathology.
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PMID:Role of the Maillard reaction in diabetes mellitus and diseases of aging. 882 Jul 92

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater).
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PMID:Vitamin E in humans: demand and delivery. 883 30


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