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)

Molecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate-enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermediate complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma.
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PMID:Modeling of substrate and inhibitor binding to phospholipase A2. 140 62

To study past histories of patients who died suddenly, we selected cases from all the summary death certificates in which death occurred within 24 hours from the onset of symptoms spanning 1984 to 1986 in Niigata prefecture with a population of 2.5 million. We then re-examined all information on the death certificates to determine the underlying causes. Sudden deaths due to cardiovascular diseases other than acute myocardial infarction and cerebrovascular accident (OCD) accounted for the largest proportion (51.4%). The proportion of death of unknown etiology increased with the decrease in age in both sexes aged 15 to 54 years, accounting for 67.8% in males and 51.1% in females. The number of cases with histories of diseases related to atherosclerosis (e.g. hypertension, old cerebrovascular accident, etc) increased with age in both sexes, accounting for 38.5% in males and 36.4% in females, both aged 75 years old and over. Except diseases related to atherosclerosis, the past histories accounted for 2.5% or greater were as follows: alcoholism (4.1%), psychiatric disorder (PSY, 2.9%) and valvular heart diseases (VD, 2.6%) in 15-54-year-old males; ischemic heart diseases (IHD, 9.4%), arrhythmia without organic heart diseases (ARR, 2.5%) and VD (2.5%) in 55-74-year-old male; IHD (11.4%), bronchial asthma (3.7%), common cold within one month (CC, 3.6%), cor pulmonale or its related diseases (3.0%) and ARR (2.6%) in male of 75 years old and over; PSY (8.7%), IHD (5.8%), VD (5.1%), pregnancy, delivery or related diseases (4.4%), chronic renal failure (3.6%) and CC (2.9%) in 15-54-year-old females; IHD (10.2%), VD (3.2%) and ARR (2.6%) in 55-74-year-old females; and IHD (11.8%) in females of 75 years old and over. When diseases related to atherosclerosis were included, half of the sudden death cases due to OCD had past histories of underlying cause. As descriptions of past histories are often incomplete, there were probably more cases with past histories. The results of this study indicate that investigation of past histories may aid in elucidating and preventing sudden death.
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PMID:[Past histories of sudden death without specific underlying disease]. 184 23

Fibrinolytic system, immune reactivity and isoelectric focusing of serum albumin were examined in 94 patients exhibiting combination of obstructive lung disease (chronic obstructive bronchitis and bronchial asthma) with atherosclerosis. Plasminogen activator showed discrete activity, the discreteness being less in respiratory distress of the I degree but higher in the distress of the II and III degree. Relative number of E-RFC and monocytes expressing receptors to IgM and IgG Fc-fragment decreased. Percentage of EAC-RFC rose. Serum albumin fractions changed pH range due to modification of albumin molecules resultant from forming complexes with fibrinogen degradation products. Concentration of the latter under conditions of respiratory distress induced by obstructive lung diseases associated with atherosclerosis substantially exceeded the standard levels.
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PMID:[Fibrinolysis, immune reactivity and the structure of the blood serum albumin in obstructive lung diseases combined with atherosclerosis]. 207 78

Since the first report by Bang and Dyerberg regarding the apparent beneficial effects of a fish oil-enriched diet on the incidence of atherosclerotic heart disease in Greenland eskimos, a considerable number of studies have been performed regarding the effects of omega-3 polyunsaturated fatty acids on the prevention and treatment of a variety of disease states not necessarily related to atherosclerosis. Studies have been performed on healthy volunteers and in patients with hyperlipidaemia, atherosclerotic vascular disease, diabetes, asthma, psoriasis and chronic renal insufficiency, amongst others. Positive effects on platelet activity, lipid profile, blood rheology and blood pressure--all factors which are presumably of importance in the pathogenesis of atherosclerotic disease have been noted in these studies, albeit with a wide range of variability. Some negative effects also appear to exist. However, some general conclusions can be made regarding the effects of a fish oil-enriched diet.
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PMID:Fish oil: a panacea? 214 59

The results of the catamnestic study of case reports and records of postmortem examination of 102 patients with bronchial asthma (BA) aged 47 to 88 years who died at a general hospital during 1976-1988 indicate that in the overwhelming majority of cases, there took place death "with asthma" rather than death "from asthma". At the same time the dominant pathology was coronary heart disease (acute coronary failure, myocardial infarction, progressive heart failure associated with atherosclerotic and postinfarction cardiosclerosis). Emphasis is laid on the fact that according to the autopsy data, the rate of the recognized stenosing atherosclerosis of the coronary arteries considerably exceeded the number of cases of coronary heart disease documented clinically (typical angina pectoris of effort, significant macrofocal myocardial infarction). The characteristic features of the group under observation included an unexpectedly frequent combination of BA and malignant neoplasms (24 cases), including lung cancer in 13 of these cases.
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PMID:[An analysis of the causes of death in bronchial asthma patients (based on the data from a 13-year prospective observation)]. 236 7

Many studies have been done to try to define new therapeutic uses for calcium antagonists, in diseases in which calcium plays a role. Positive results have been obtained in the prevention of acute attacks of idiopathic Raynaud's disease and migraine, and in effort-induced asthma. Some activity could be demonstrated in selected groups of patients with pulmonary hypertension, manic-depressive illness, untractable epilepsy, various functional gynecological or digestive disorders, and in drug-induced nephrotoxicity. A possible effect on the prevention of resistance to anti-cancer drugs could be of major interest. Their antiplatelet effect, and their possible effect against atherosclerosis, which remains to be confirmed, their lack of side-effects in asthmatics and of interference with glucose regulation increase their usefulness in patients with hypertension or ischemic heart disease, especially when other diseases are present.
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PMID:[Use of calcium inhibitors excluding cardiac pathology and arterial hypertension]. 267 79

A 34-year-old man with allergic asthma died an (instantaneous) sudden cardiac death as a result of multiple myocardial infarcts. These occurred in the absence of coronary atherosclerosis. The major mechanism by which the infarcts occurred was recurrent coronary artery spasm. The latter can occur spontaneously, asthma patients being particularly prone to it. However, various medications prescribed by different physicians may also have played a role.
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PMID:Fatal nonatherosclerotic myocardial infarction in a young man with allergic bronchial asthma. 379 70

P-selectin is a transmembrane adhesion receptor specific to platelets and endothelial cells. It has an N-terminal lectin domain that recognizes specific carbohydrate moieties on monocytes, neutrophils and some other subsets of leukocytes. P-selectin is stored in granules and is expressed on the plasma membrane only after the cells are stimulated by vascular injury or during inflammation. Physiologically P-selectin is likely to be involved in the recruitment of leukocytes that promote wound healing and fight infection. There are many disorders in which the excessive recruitment of leukocytes is characteristic, including chronic inflammation, atherosclerosis, arthritis, diabetes, asthma and reperfusion injury. Because certain cancer cells also express the ligand for P-selectin it is possible that this receptor is involved in metastasis. To study the specific role of P-selectin in these pathological processes, we have prepared a mouse lacking P-selectin through gene targeting. Leukocyte interaction with the vessel wall is defective in these animals as leukocytes do not roll in the mesenteric venules and their extravasation at sites of inflammation and vessel injury is limited. We are testing these animals in models of the various diseases mentioned above in order to evaluate when the absence of P-selectin is beneficial.
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PMID:P-selectin knockout: a mouse model for various human diseases. 758 33

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.
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PMID:The role of free radicals in disease. 761 52

1. Heparin belongs to a family of polysaccharide species, whose best known property is, undoubtedly, anticoagulant activity. However, heparin has many other pharmacological effects, particularly on the cardiovascular system. 2. The therapeutic use of chronically inhaled heparin has been suggested as prophylaxis in atherosclerosis. 3. Heparin, physiologically stored in mast cells of the respiratory system, has also been recently studied in the prevention of immunological and non-immunological asthmatic attacks. 4. Experimental findings and new hypotheses of heparin action in asthma and atherosclerosis are discussed.
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PMID:Heparin: pharmacological potentials from atherosclerosis to asthma. 763 44


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