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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The atheromas of adult aortas have been found to be composed mostly of tabular crystals of a highly insoluble cholesterol-cholestanol-water adduct designated C-C-2W. Early feeding of cholestanol risks precipitation of C-C-2W on the incomplete membranes of infants. Resultant impairment of cell permeability and reactivity can give rise to incipient atherosclerosis. The pathological condition becomes patent only with adulthood, when the aorta intima-media will be stacked with the adduct and fatty streaks will occur. Cholesterol, as provided by the usual dietary sources, contains from 3 to 10% of cholestanol, quantities more than sufficient to reach the solubility product of C-C-2W: 10(-7) mg/ml. It follows that much atherosclerosis could be avoided if cholestanol-containing foods, specifically dietary cholesterol, were not fed to infants or children. Cholestanolosis and hypercholestanolemia are new concepts to be considered in dietary approaches to control of atherosclerosis.
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PMID:Feeding cholestanol to infants causes atherosclerosis. 54 1

Cerebrotendinous xanthomatosis (CTX) is a rare familial lipid storage disease caused by defective bile acid synthesis. As a result, cholestanol, a derivative of cholesterol, is accumulated by virtually every tissue, predominantly by the nervous system, xanthomas and bile. Clinically, progressive neurologic dysfunction, tendon xanthomas, cataracts, osteoporosis and atherosclerosis are commonly found. Replacement therapy with chenodeoxycholic acid (750 mg/day), a primary bile acid, which is almost absent from the bile in CTX, reduces elevated cholestanol synthesis and concentrations and improves neurologic function in this disease.
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PMID:[Cerebrotendinous xanthomatosis]. 133 99

Cholesterol is converted to cholic acid and chenodeoxycholic acid by a series of reactions involving modifications to the steroid nucleus and oxidation of the side chain. These reactions can be affected by a number of inborn errors of metabolism. When this happens unusual bile acids or bile alcohols are synthesized; these can be identified using gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry techniques. Two defects affecting the modifications to the steroid nucleus have been described; both present with cholestatic liver disease of neonatal onset. The better characterized of the two--3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency--leads to excretion of 3 beta-7 alpha-dihydroxy-5-cholenoic acid and 3 beta,7 alpha,12 alpha-trihydroxy-5-cholenoic acid in the urine. The liver disease improves dramatically on treatment with chenodeoxycholic acid. Deficient activity of 3-oxo-delta 4-steroid 5 beta-reductase is thought to be the cause of familial liver disease in some infants who excrete 7 alpha-hydroxy-3-oxo-4-cholenoic acid and 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid in the urine. However, diagnosis of this disorder is problematical; a similar pattern of metabolite excretion can occur as a result of liver damage caused by viruses or inborn errors of pathways unrelated to bile acid synthesis. Defective side chain oxidation in patients with cerebrotendinous xanthomatosis (CTX) leads to synthesis of bile alcohols such as 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol. Patients with CTX do not have cholestatic liver disease. Their major problems (neurological disease, atherosclerosis and xanthomata) are caused by accumulation of cholestanol and cholesterol in the tissues. Bile acid precursors are probably diverted into synthesis of cholestanol. Chenodeoxycholic acid suppresses the production of abnormal metabolites from cholesterol (by inhibition of cholesterol 7 alpha-hydroxylase) and leads to improvement in the neurological disease. Defective side chain oxidation also occurs in peroxisomal disorders but this time it leads to accumulation of C27 bile acids such as 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (trihydroxycoprostanic acid, THCA). This compound is readily detected in the bile and plasma of patients with defects of peroxisome biogenesis. In patients with defects of a single peroxisomal beta-oxidation enzyme (the 3-hydroxyacyl-CoA component of the bifunctional protein or the thiolase), the major C27 bile acid in bile may be 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid (varanic acid).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inborn errors of bile acid metabolism. 174 14

The authors report the clinical findings in 10 Italian cases of cerebrotendinous xanthomatosis (CTX). In addition to the classical neurological manifestations, the presence of psychiatric symptoms and osteopenia is stressed. Chronic treatment with chenodeoxycholic acid resulted in decreased plasma cholestanol levels and improvement of some central and peripheral neurophysiological parameters including EEG, VEP, SEP and conduction velocities. Due to the presence of cataracts, ischemic heart disease, premature atherosclerosis, mental deterioration and osteoporosis, usually found in old age, CTX can be considered a useful model of premature ageing.
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PMID:Cerebrotendinous xanthomatosis as a multisystem disease mimicking premature ageing. 181 44

We reported a 53-year-old woman with hypothyroidism due to ectopic thyroid gland. She showed intellectual impairment, bilateral pyramidal tract sings, slight cerebellar signs, and degenerative changes of brain white matter on CT and MRI, which were similar to symptoms and signs in cerebrotendinous xanthomatosis (CTX). We found increases of serum cholestanol in the patient and additional 3 patients with hypothyroidism. Total bile alcohol was also increased in the serum of the patients. We speculate that hypothyroidism and CTX might have a similar pathophysiological background on the development of neurological complications and atherosclerosis.
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PMID:[Hypothyroidism with increased serum levels of cholestanol and bile alcohol--analogous symptoms to cerebrotendinous xanthomatosis]. 191 25

In a study of coronary artery disease in patients with cerebrotendinous xanthomatosis (CTX), we documented the presence or absence of atherogenic risk factors and performed detailed analyses of serum lipid and lipoprotein profiles. Four of the seven patients examined had coronary arterial narrowing and/or obstruction, but multiple atherogenic risk factors were not found in any of these patients. Total cholesterol (T.ch) levels and low density lipoprotein-cholesterol (LDL-ch) levels were lower, and high density lipoprotein2-cholesterol (HDL2-ch) levels were higher in CTX patients than in controls. Triglyceride and very low density lipoprotein (VLDL) levels were significantly lower in the former. Indices correlating with the risk of atherosclerosis, such as the atherogenic index, and the ratios of apolipoprotein B/apolipoprotein AI, HDL2-ch/LDL-ch, HDL2-ch/HDL3-ch, indicated that CTX serum was, in fact, 'anti-atherogenic'. However, coronary artery disease is frequently seen in patients with CTX. This discrepancy suggests the existence of a unique mechanism by which atherosclerosis is induced in patients with CTX. We discuss a mechanism of disturbed lipoprotein metabolism which might be responsible for the deposition of sterols in the tissues of patients with CTX.
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PMID:Atherogenic risk factors in cerebrotendinous xanthomatosis. 193 6

The sterol storage disorder cerebrotendinous xanthomatosis (CTX) is characterized by abnormal deposition of cholesterol and cholestanol in multiple tissues. Deposition in the central nervous system leads to neurological dysfunction marked by dementia, spinal cord paresis, and cerebellar ataxia. Deposition in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In two unrelated patients with CTX, we have identified different point mutations in the gene (CYP27) encoding sterol 27-hydroxylase, a key enzyme in the bile acid biosynthesis pathway. Transfection of mutant cDNAs into cultured cells results in the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished enzyme activity. We have localized the CYP27 gene to the q33-qter interval of human chromosome 2, and to mouse chromosome 1, in agreement with the autosomal recessive inheritance pattern of CTX. These findings underscore the essential role played by sterols in the central nervous system and suggest that mutations in other sterol metabolizing enzymes may contribute to diseases with neurological manifestations.
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PMID:Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. 201 2

We present the clinical and laboratory findings of 8 patients with cerebrotendinous xanthomatosis. The clinical features consisted of a combination of bilateral Achilles tendon xanthomas, cataracts, low intelligence, pyramidal signs, cerebellar signs, convulsions, peripheral neuropathy, foot deformity, cardiovascular disease or atherosclerosis, EEG abnormality, and increased CSF protein. Increased cholesterol was present in the serum, CSF and red cell membrane of all 8 patients. The bile of one patient with late age onset of the disease showed an attenuated production of bile acids and bile alcohols. Three of the 7 had obstruction and/or marked narrowing of the coronary arteries. Data on 136 patients reported throughout the world are reviewed.
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PMID:Cerebrotendinous xanthomatosis: clinical and biochemical evaluation of eight patients and review of the literature. 207 21

Cerebrotendinous xanthomatosis is a rare familial lipid storage that is caused by a defect in bile acid synthesis. As a result, large amounts of cholestanol, the 5 alpha-dihydro derivative of cholesterol, accumulate in virtually every tissue, with extra large deposits in the nervous system, xanthomas, and bile. Clinically, progressive neurologic dysfunction, tendon xanthomas, cataracts, and atherosclerosis are commonly found. Because chenodeoxycholic acid, a primary bile acid, is almost devoid from the bile, replacement therapy (750 mg per day) suppresses abnormal bile acid synthesis, reduces elevated cholestanol synthesis and plasma concentrations, and improves neurologic function in this disease.
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PMID:Cerebrotendinous xanthomatosis. 249 65

Rabbits were fed diets enriched with cholestanol or cholesterol (3.5 g/wk) for 4-12 weeks. During cholestanol feeding, the concentration of cholestanol in blood serum, liver, heart and aorta increased 15-30 times. In serum and liver, the concentration of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally seen in rabbits receiving cholestanol for eight weeks or less. During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis.
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PMID:Effects of cholestanol feeding and cholestyramine treatment on the tissue sterols in the rabbit. 382 87


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