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)

A 48 year old male patient presented with xanthomatosis, hyperbeta lipoproteinemia and hyper-IgA globulinemia; these two serum components occurred as a "complex." The patient has subsequently been studied for 22 years (1952 to 1974). His serum cholesterol and triglyceride levels have been consistently and excessively high despite efforts to regulate them by means of diet or diet and drugs. Serum immunoglobulin A (IgA) concentration ranged from 1,400 to 3,400 mg/dl compared with a normal value of 156 plus or minus 92 mg/dl. The metabolism of lipoproteins, judged by vitamin A turnover studies was slow. Peripheral atherosclerosis became evident 15 years after beginning the study whereas cinecoronary arteriography concurrently demonstrated only minimum changes. Xanthomas exhibited marked regression only during the last 6 years, after 16 years of diet and the addition of clofibrate for 7 years. Beta lipoprotein and IgA globulin determined by immunofluorescent and immunoelectrophoretic technics were demonstrated in the atherosclerotic material obtained from the patient's arterial wall. They were also found in the plasma cells of the bone marrow. The IgA globulin-beta lipoprotein complex in the serum was broken with difficulty. The patient's isolated IgA globulin, free of lipoprotein, formed a firm complex when mixed with beta lipoprotein prepared from normal human serum. Initially, IgA globulin studies showed presence of both kappa and lambda light chains in normal proportion. But after 18 years, the IgA globulin has become monoclonal, type lambda. The plasma cells of the bone marrow have become progressively more atypical and immature. No clinical indications of multiple myeloma have been found. It is concluded that association of lipoproteins with IgA globulin in the serum of this patient with hyperlipidemia, hyper-IgA globulinemia did not prevent the development of atherosclerotic lesions and the deposition of lipids and lipoproteins in the plaques. It is possible that the lipoprotein-immunoglobulin association may have retarded the process, since it became manifest only after many years of known hyperlipidemia.
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PMID:Autoimmune hyperlipidemia in a patient. Atherosclerotic course and chaning immunoglobulin pattern during 21 years of study. 16 71

Histological, histochemical and electron-microscopical examinations have been performed on xanthoma of the skin and palmar creases in 5 patients with hyperlipoproteinemia type III, to follow the dynamics of xanthoma formation. The results were as follows: 1. There are no basic differences in histomorphology between xanthomas in type III-HLP and other types of HLP. Typical findings are: Rather dense distribution of relatively small foam cells within the dermis, only a few foam giant cells, great amounts of cholesterol intra- and extracellulary, and circumscribed necrobioses. 2. Xanthoma formation in type III-HLP is induced by pathological plasma lipoproteins. These seem to pass the endothelial barrier via pinocytosis or/and filtration. Between endothelial cells and their basal lamina plasma components sometimes could be observed. 3. The pathological lipoproteins induce a phagocytic reaction with foam cell formation in the dermal tissue. At first an augmentation of lymphocytoid or histiocytoid tissue macrophages could be detected in the dermis and especially in the perivascular region of venous blood vessels in the middermis. Perithelial cells as well as lymphocytoid and histiocytoid tissue macrophages engulve lipoproteins. Cytoplasmic enrichment of vacuoles with an electron opaque content (lipoproteins) are typical for type III-HLP; they lead to formation of typical foam cells. Within those cells lysosomal intracellular degradation of the engulved lipoproteins takes place; free cholesterol cristals, phospholipid-containing myelinic figures and residual bodies are endproducts of this process. They can lead to cellular necrosis with cellular remnants, lipoprotein vacuoles, free cholesterol and phospholipids lying free within the dermal tissue. 4. Factors are not well understood which control circumscribed xanthoma formation in type III-HLP. 5. These investigations show, that xanthomas are reactive new formations. The leading cellular substrate is the tissue macrophage, which is transformed into a foam cell by intake of lipoproteins. Foam cell formation, however, is not the result of a simple process of storage: after lipoprotein intake numerous, to a part lysosomal processes of chemical degradation and transformation, take place with an appearance of intracellular endproducts (free cholesterol, residual bodies, phospholipid-containing membranes). It is suggested that the dynamics of xanthoma formation might be importance in understanding of the process of atherosclerosis in those patients.
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PMID:[Sturcture and morphogenesis of xanthomas in hyperlipoproteinemia type III. A morphologic, histochemical and electron microscopy study]. 17 29

Forty-six patients with xanthomatosis and elevated very low density lipoproteins (VLDL) levels (in different types of hyperlipoproteinaemia) were classified on the basis of the WHO criteria and the cholesterol/triglyceride ratio in VLDL. A large majority (31/46) of the patients referred to the Department of Dermatology could be classified as hyperlipoproteinaemia type III, only 8/46 as type IIB and 7/46 as type IV/V. This distinction seems to be relevant as the xanthomatous lesions differed distinctly between these three types of hyperlipoproteinaemia. Xanthochromia striata palmaris was present in 29/31 cases of hyperlipoproteinaemia type III and was not found in type IV/V patients, who had distinctive papuloeruptive xanthomas. During a follow-up in 35/46 patients all xanthomas disappeared within 2 years except the xanthelasma palpebrarum and tendinous xanthomas. All type IV/V patients (7/7) but only one type III patient (1/31) had abnormal glucose tolerance. Only 2/18 type III patients less than 45 years showed claudication and none of the young type III patients had angina pectoris. In contrast, all four type IIB patients less than 45 years had clinical signs of atherosclerosis. However, angina pectoris and/or claudication were present in 5/13 type III patients over 45 years old. The mean serum cholesterol level was equally elevated in both groups but the cholesterol was mainly present in VLDL in type III and in low density lipoproteins (LDL) in type IIB. In 9/31 type III patients the LDL level was also elevated but was easily normalized by a diet low in carbohydrate, whereas the elevated LDL level in type IIB was therapy-resistant. The recognition of xanthomatous lesions, specifically xanthochromia striata palmaris, as an early sign of type III hyperlipoproteinaemia, can lead to the early diagnosis and successful treatment of these patients, and thus possibly prevent the development of premature atherosclerosis.
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PMID:Xanthomatosis and other clinical findings in patients with elevated levels of very low density lipoproteins. 22 20

Two patients with nomozygous familial hypercholesterolemia, refractory to medical therapy, underwent complete bile diversion by common-duct ligation and cholecystostomy, in an attempt to arrest the progression of their xanthomatosis and atherosclerosis by depletion of body cholesterol. Clofibrate was given after operation to one patient, and cholic acid to both, in an effort to enhance further the negative sterol balance. Bile diversion produced an increase of six to eight times in gastrointestinal sterol output, which was not increased further by either clofibrate or cholic acid therapy. Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased. Continuity of the biliary tree was therefore restored. The data suggest that patients with homozygous familial hypercholesterolemia respond to even massive gastrointestinal sterol depletion with equal increases in sterol synthesis.
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PMID:Failure of complete bile diversion and oral bile acid therapy in the treatment of homozygous familial hypercholesterolemia. 83 24

Homozygous familial hypercholesterolaemia is characterized by cutaneous xanthoma development from infancy, precocious and accelerated atherosclerosis with clinical signs of ischemic heart disease and frequent involvement of left heart valves resulting in stenosis and/or incompetence. Two cases are described of this condition, both associated with aortic stenosis. In one case mitral incompetence and thromboembolic pulmonary hypertension were also found. The mitral valve is involved in the atherosclerotic process at the level of the cusps. These become thickened and stiff. Aortic stenosis is mainly due to atheromas infiltrating the Valsalva sinuses and the ascending aorta. Pulmonary hypertension, never reported before in this disease, is probably due to concomitant atheromatosis involving the pulmonary artery with secondary fatty embolism.
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PMID:[Involvement of the heart valves and great vessels in homozygote familial hypercholesterolemia]. 129 17

We present a normolipaemic young man with extensive facial plane xanthomas and xanthelasmas with a high level of lipoprotein(a) and possibly increased vascular permeability. These associations are of potential importance in understanding the pathogenesis of xanthoma formation and in the identification of patients at risk from coronary atherosclerosis.
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PMID:Normolipaemic plane xanthomas: an association with increased vascular permeability and serum lipoprotein(a) concentration. 145 6

A family with multiple spinal xanthomas and sitosterolemia is described. A 48-year-old woman presented with paraplegia due to multiple intradural extramedullary tumors. The patient also showed marked tendon xanthomas and analysis of sterol composition in both plasma and the xanthoma established the diagnosis of the rare inherited metabolic disease, sitosterolemia and xanthomatosis. Two other siblings in the family presented with marked tendon xanthomas and coronary atherosclerosis, but did not show any neurological signs or symptoms. Magnetic resonance imaging (MRI) study revealed multiple intradural extramedullary tumors in spinal canals of the proband and her sister, but not in the other affected sibling (brother). This is the first report of familial occurrence of multiple extramedullary spinal tumors due to the inherited metabolic abnormality.
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PMID:Familial spinal xanthomatosis with sitosterolemia. 147 63

A case showing the regression of coronary atherosclerosis by the treatment with LDL-apheresis, was reported. The patient was a 67-year old female with heterozygous familial hypercholesterolemia. She had noticed the xanthelasma or left cubital xanthoma at the age of 50 years old. She was informed about her high serum cholesterol level (greater than 350 mg/dl), and the abnormal thickness of her bilateral achilles tendon at the age of 61 years. As her serum cholesterol level did not decrease sufficiently with several lipid-lowering drugs, she was referred to our hospital in order to obtain treatment for it by LDL-apheresis at the age of 66 years. LDL-apheresis was performed once every two weeks with drugs such as probucol, cholestyramine and pravastatin. Her coronary angiogram after two and half years of LDL-apheresis showed a decrease of the coronary narrowing in segment 1 and segment 13 (from 96.8% to 74.6% in segment 1, and from 81.5% to 61.7% in segment 13, respectively). The thickness of her bilateral achilles tendons had also decreased from 18 mm in the right and 19 mm in the left to 14 mm in both, after receiving LDL-apheresis for two and half years. It is suggested from the result of this case that the regression of coronary atherosclerosis could be expected after treatment with LDL-apheresis in hypercholesterolemic patients.
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PMID:[A case of heterozygous familial hypercholesterolemia showing the regression of coronary atherosclerosis by LDL-apheresis]. 157 54

Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine (3500)----glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine(3500)----glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine(3500)----glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to "classic" familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor-defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100.
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PMID:Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia. 160 Mar 34

Atherosclerosis is a fundamental cause of life-threatening disorders, such as ischemic heart disease or stroke. Therefore, prevention and treatment of atherosclerosis is a matter of importance. In atherosclerotic lesions, there are many foam cells which contain large amounts of cholesteryl ester. In particular, most of these foam cells in the early stage of atherosclerosis derive from monocytes/macrophages. Today, foam cell transformation of macrophages in subendothelial space is considered to occur by a mechanism in which macrophages take up oxidized low density lipoprotein. We have already discovered that atherosclerosis of Watanabe heritable hyperlipidemic rabbits, an animal model for hereditary hyperlipidemia and severe atherosclerosis, could be prevented by probucol. This drug was originally developed as an antioxidant, and the mechanism of prevention of atherogenesis with this drug is considered that it prevents oxidative modification of LDL. On the other hand, probucol also causes regression of xanthoma in patients with familial hypercholesterolemia. This effect implies that probucol can be effective for treatment of atheromatous lesions, because xanthoma is a lesion which consists of macrophage-derived foam cells. However, the precise mechanism of probucol in causing regression of xanthoma has not been clarified. Considering these observations, we paid special attention to the oxidative modification of high density lipoprotein (HDL). HDL makes contact with foam cells in subendothelial space and stimulates efflux of cholesterol. This is the very place where oxidative modification of LDL is considered to occur. Therefore, it is rational to attempt to determine what would happen when HDL is oxidized and whether probucol could prevent oxidative modification of HDL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on atherosclerosis with an animal model]. 161 1


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