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

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

The incidence of ischaemic diseases in familial hypercholesterolaemia and xanthomatosis (familial Type II) was studied in a group of 158 men and 116 women. (1) Men and women did not differ with regard to the inherited metabolic disease. Levels of serum cholesterol, the marker of the genetic defect, were not statistically different, and cholesterol deposition in tissues, visualized by skin tendon xanthomas, was not sex related. (2) Men and women were different with regard to ischaemic diseases. The incidence was much lower in women, and the mean age of onset 9 years later. Moreover, there was a sex difference in the nature of the ischaemic disease, with a high male predominance of myocardial infarction. (3) Since the major risk factor hypercholesterolaemia could not explain such a difference, the role of other risk factors was investigated. It was shown that the incidence of ischaemic diseases was increased in women by cigarette smoking and hypertension, and that the difference in age of onset between males and females was no longer seen in smoking women. It is suggested that the genetic factor is responsible for the atherosclerotic lesion in both sexes and that other factors playing a role in ischaemic complications including tobacco and hypertension may explain the difference between men and women.
Atherosclerosis 1976 Sep
PMID:Ischaemic disease in men and women with familial hypercholesterolaemia and xanthomatosis. A comparative study of genetic and environmental factors in 274 heterozygous cases. 97 46

The morbidity and mortality in 172 males and 164 females with xanthomatosis have been investigated. Symptoms of coronary heart disease (CHD) were the most frequent initial manifestation of atherosclerotic vascular disease. Angina pectoris was the first symptom in about 3/4 of males as well as females; myocardial infarction was the first event in 26% of the males and 9% of the females. Other manifestations of atherosclerosis were comparatively rare and occurred late in life. Half of the subjects were affected with symptoms of atherosclerotic vascular disease by the age of 52 in men and 62 in women, the mean age for first symptoms being 49 and 56 years, respectively. No significant influence of other CHD risk factors than xanthomatosis and hyperlipidaemia was found in these patients. An increase in the number of cardiovascular deaths was seen in xanthomatosis patients, compared with the general population, in particular in the number of "sudden deaths". Half of the males died before the age of 66 and half of the females before the age of 74.5, which is about 10 and 7 years earlier than predicted at 30 years of age for the normal population. The cumulative relative mortality in both men and women was about twice that expected for the general Norwegian population until 70 years of age.
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PMID:The risk of atherosclerotic vascular disease in subjects with xanthomatosis. 118 82

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

Experimental approaches to the problem of atherosclerosis involve animal or cellular models and procedures of lesional induction. Relevant animal models are rare. The rat, the mouse and the dog are free of "natural" atherosclerosis and only develop diffuse lipidosis after high cholesterol diet and thyroid block. They are more appropriate models of experimental arteriosclerosis and intimal proliferation induced by different procedures. The rabbit, also free of spontaneous atherosclerosis, is extremely sensitive to lipid-rich diets, but the lesions induced resemble more a xanthomatosis than an atherosclerosis. Immunological procedures in this model result in a generalised immune arteriosclerotic arteriopathy. The monkey and pig, which are phylogenetically close to man, develop spontaneous atherosclerosis exacerbated by lipid-rich diets or other procedures: hormones, psychosocial stress. The cost and problems of upkeep make these two models inaccessible to most laboratories. Although the hen, turkey and pigeon are grain-eating, they develop natural atherosclerosis, are sensitive to atherogenic diets, and provide satisfactory replacement models, especially for research into the viral and tumoral theories of atherogenesis. The pigeon is particularly suitable for studying cellular, biochemical and genetic aspects of atherosclerosis: these spontaneous plaques, similar to those in man, are ontogenetically and topographically predictable. The species include genetic types both sensitive and resistant to the disease. Moderately lipid-rich diets induce lesions even in very young pigeons. They also lend themselves well to the study of the antiatherosclerotic effects of pharmacological agents. Endothelial, smooth muscle and macrophage cell cultures are widely used to study the factors influencing cellular modulation and proliferation, lipid metabolism and movement of cholesterol, cellular biosynthesis and cell-cell and cell-matrix interactions.
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PMID:[Experimental models of atherosclerosis. Contribution, limits and trends]. 176 26

Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol-free formula or low plant sterol diet in three patients. The average half-life of the first exponential (tA1/2) for sitosterol was 9.2 +/- 3.3 (mean +/- SD) days, which was more than twice that in normal humans. The second exponential (tB1/2) was 156 +/- 108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, which is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterol-mixed food diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. 191 14

In this report, an 11-year-old boy with diffuse tendinous and tuberous xanthomatosis and a plasma sterol concentration of 555 mg/dL, consisting primarily of cholesterol, is described. Three months after changing from an unrestricted diet to a cholesterol-lowering diet, his plasma sterol concentration decreased to 221 mg/dL. Because of the degree and rapidity of his response to diet, sitosterolemia was suspected. According to results of capillary gas-liquid chromatography of his plasma sterols, there was a sitosterol concentration of 31.3 mg/dL (normal less than 1.0 mg/dL), establishing the diagnosis of sitosterolemia. Addition of cholestyramine therapy (8 g/d) to a low sterol diet further lowered his plasma sterol concentration to 173 mg/dL and led to complete regression of all tuberous xanthomata. Tendinous xanthomata regressed at a slower rate. These findings show that the diagnosis of sitosterolemia should be suspected in severely hypercholesterolemic children (total cholesterol greater than 400 mg/dL) whose plasma cholesterol level is highly responsive to dietary manipulation. The rapid and sustained lowering of plasma cholesterol and regression of xanthomata after treatment with diet and cholestyramine suggest that sitosterolemia is a treatable cause of premature atherosclerosis.
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PMID:Response to diet and cholestyramine in a patient with sitosterolemia. 225 Oct 34

We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor-mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease.
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PMID:Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. 231 63


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