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)

Plasma sterol levels in a family of sitosterolemia and xanthomatosis were determined by a high performance liquid chromatography. Three affected siblings manifested marked xanthomatosis including subcutaneous soft tissues and generalized atherosclerosis. Two other siblings as well as children of the patients did not show such clinical symptoms and signs. Plasma levels of cholesterol, sitosterol, campesterol, and cholestanol in three affected subjects were 190 +/- 18.5, 25.9 +/- 11.6, 16.1 +/- 7.8, 1.84 +/- 0.92 mg/dl (mean +/- SD), respectively. Four daughters of the affected subjects, who should be considered as obligatory heterozygotes, showed moderately increased levels of these sterols (195 +/- 41.7, 1.33 +/- 0.44, 1.56 +/- 0.69, 0.80 +/- 0.28 mg/dl), which were significantly higher than those of normal subjects. Treatment with cholestyramine had little effect on the increased plasma plant sterol levels, but markedly decreased plasma cholestanol concentrations in two affected siblings. This report presents the clinical features of the patients with sitosterolemia and xanthomatosis and also demonstrates that heterozygotes with this disorder have increased plasma levels of plant sterols as well as cholestanol, and suggests that this rare disease might be inherited as an autosomal co-dominant trait in certain cases. The data also indicate that cholestyramine administration was not effective in this family for treatment of sitosterolemia.
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PMID:Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. 238 Jun 36

A new modification of enzyme immunoassay: enzyme-linked-immunoreceptor assay (ELIRA)--was used to study the activity of LDL-receptors on cultured fibroblasts from 10 patients with elevated plasma cholesterol levels, IHD, accelerated atherosclerosis and xanthomatosis. Four patients were found to have heterozygous form of familial hypercholesterolemia. We have also shown that the results of ELIRA were quantitatively similar to the data obtained by traditional radioisotopic method. This indicates that simple, rapid, inexpensive ELIRA can be used for diagnosis of FH.
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PMID:[An immunoenzyme method of diagnosing familial hypercholesterolemia]. 304 91

We have experienced two autopsy cases of familial hypercholesterolemia of type IIa homozygote, one was a 21-year-old female with a defect in the internalization of low density lipoprotein which is thought to be the first autopsy report in the world, and the other was a 31-year-old male with a receptor negative for low density lipoprotein. Autopsy findings, in addition to marked skin xanthomatosis, disclosed reversed distribution of the aortic atherosclerosis, diffuse atherosclerotic narrowing of coronary arteries which led to myocardial necrosis, xanthomatous aortic and mitral valve, and much less severity of cerebral arteries rather than that of aorto-coronary atherosclerosis. We have examined the apolipoprotein B accumulation on these aortas, coronary arteries, and cardiac valves, which showed better correlation between apolipoprotein B deposit areas and preferential accumulation of Alcian blue positive areas suggested to contain sulfate glycosaminoglycan, and documented very rare localization of renal and osseous xanthomas in a patient with internalization defect of low density lipoprotein.
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PMID:Autopsy findings in two patients with homozygous familial hypercholesterolemia. Special references to apolipoprotein B localization and internalization defect of low density lipoprotein. 312 Apr 90

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia (P less than 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not (P less than 0.01), and in patients with corneal arcus (P less than 0.0001), ischaemic disease (P less than 0.01), tendon xanthomas (P less than 0.05) or xanthelasma (P less than 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp (r = 0.78; P = 0.013) and IgG Lp (r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.
Atherosclerosis 1988 Dec
PMID:Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis. 324 Mar 31

The hypothesis that abnormal low density lipoprotein (LDL) sterol content and composition in sitosterolemia with xanthomatosis affects LDL uptake and/or degradation was tested. Monocytes and lymphocytes from three patients and 12 age- and sex-matched controls were incubated at 37 degrees C in lipid-free medium with 125I-labeled LDL prepared from sitosterolemic patients (LDLs) and controls (LDLn) in the presence or absence of excess unlabeled lipoproteins. Normal monocytes and lymphocytes took up and degraded LDLs 13% to 30% less than LDLn (P less than .05). Sitosterolemic monocytes and lymphocytes degraded LDLn 13% and LDLs 67% more actively than control cells (P less than .05). Sitosterolemic monocytes contained three times more sterols and stanols than controls (P less than .01), of which 12% were plant sterols and 2% were 5 alpha-saturated stanols. In one patient, stimulating bile acid synthesis by ileal bypass surgery reduced plasma and monocyte sterol and stanol concentrations about 60%, and was associated with a 40% to 50% increase in LDLn and LDLs receptor-mediated degradation. The decreased uptake and degradation of LDLs relative to LDLn by normal cells suggest that abnormal plant sterols in LDLs may reduce its affinity for the native LDL receptor. Increased receptor-mediated uptake and degradation of LDLs by sitosterolemic cells in the presence of high cellular sterol content may result from failure of the sitosterolemic cells to down-regulate LDL receptor synthesis. Ileal bypass surgery increased cellular LDL receptor activity, reduced plasma and cellular sterol concentrations, and may diminish the risk of premature atherosclerosis in sitosterolemia.
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PMID:The effect of abnormal plasma and cellular sterol content and composition on low density lipoprotein uptake and degradation by monocytes and lymphocytes in sitosterolemia with xanthomatosis. 335 17

This report describes a 72-year-old female patient with 2 types of severely disfiguring xanthomas, particularly on the facial area and the upper arms. Biopsy revealed xanthoma-type cells, histiocytes, and multiple giant cells. The soft yellowish facial xanthomata were rich in esterified cholesterol, whereas the cholesterol content of the colorless, firm, fibrous xanthoma of the arms was relatively low. The clinical course of insidiously starting polyarthritis, the formation of skin and tendon xanthomas (at the age of 63) and, finally, the histological findings verified the diagnosis of multicentric reticulohistiocytosis. The family history and findings were noncontributory. The patient had symptoms of moderate coronary heart disease and died from an acute myocardial infarction. Her total cholesterol and triglyceride levels were 182 and 89 mg/dl, and the HDL cholesterol value was 43 mg/dl. Plasma levels of apolipoprotein A-I, A-II and B were normal, and her apoprotein E pattern was E3/E3. The triglyceride/cholesterol ratio of VLDL, the concentration of apo-LDL (LDL protein) and the LDL-protein/cholesterol ratio were normal. The apo-LDL production, the total clearance rate of apo-LDL, and the receptor-mediated and receptor-independent catabolism of LDL were also normal. Fecal output of neutral sterols and bile acids and the total body cholesterol synthesis were normal, but cholesterol absorption tended to be increased. The response to cholestyramine treatment showed a 44% decrease in the serum cholesterol level and a normal 5-fold increase in cholesterol synthesis. The patient's xanthoma formation could not be associated with any of the causes known to promote the development of normolipidemic xanthomatosis. It is suggested that multicentric reticulohistiocytosis should be considered in the differential diagnosis of patients with normolipidemic xanthomatosis.
Atherosclerosis 1987 Dec
PMID:Multicentric reticulohistiocytosis, another lipid disorder with normolipidemic xanthomatosis? 342 52

Interstitial fluid (IF) was obtained in 27 apparently healthy subjects (12 males, 15 females) by applying mild suction (200-250 mm Hg) on the skin either on the midvolar forearm or on the paraumbilical region of the abdomen. The IF concentrations of lipids and apolipoproteins (apo) were studied and compared with those of serum (S). The mean ratio between interstitial fluid and serum (IF/S ratio) varied from 0.14 for forearm apoE to 0.29 for apoA-II on the abdomen. This ratio was consistently lower for apoE, C-II, C-III, and B than for apoA-I and A-II, and significantly lower on the arm than on the abdomen for all apolipoproteins studied. The IF/S ratios showed marked variations among individuals. However, interstitial fluid apolipoprotein concentrations at different blister sites were highly correlated within each individual. Studies with agarose gel electrophoresis and density gradient ultracentrifugation revealed that large triglyceride-rich particles were virtually lacking in interstitial fluid and that the relation between the low density lipoproteins (LDL) and high density lipoproteins (HDL) was shifted towards a greater proportion of HDL. The lipoprotein distribution in the HDL range of interstitial fluid differed from that of serum showing one maximum at a density of about 1.070 g/ml (serum HDL2 about 1.090 g/ml) and one at a density of 1.130-1.140 g/ml (serum HDL3, 1.110-1.120 g/ml). The former subfraction contained most of the lipoprotein-bound apoE while the latter contained the major part of apoA-I and apoA-II. Studies of the lipoproteins of interstitial fluid may add to our understanding of the development of atherosclerosis and xanthomatosis and may also provide valuable information on the permeability of the capillary membrane in normo- and pathophysiological states.
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PMID:Lipoprotein composition of human suction-blister interstitial fluid. 361 67

We previously reported the finding of phytosterolemia, xanthomatosis, and hyperapobetalipoproteinemia (hyperapoB) in five siblings in a large Amish pedigree ascertained through a 13-year-old boy who died suddenly from advanced coronary atherosclerosis. Here, we present further analyses of the plasma levels of the plant sterol, sitosterol, of low density (beta) lipoprotein (LDL) sterol, and of LDL B protein. Of 254 relatives and spouses of the proband, 90.5% were examined. A series of genetic models were explored using a pedigree analysis where parameters reflecting frequency, transmission, and penetrance of putative genotypes were examined simultaneously using a maximum likelihood approach. Segregation analysis of the sitosterol levels showed that the phenotype of sitosterolemia was controlled by a rare autosomal recessive gene. There was also significant familial correlation in plasma sitosterol levels that was attributed to a polygenic component under a mixed model but could also be due to shared environments such as diets. The recessive model was supported by our finding that the plasma sitosterol levels in the parents and in six children born to three of the five sitosterolemics were less than 1 mg/dl, well within the normal range. The phenotype of hyperapoB is based on an elevated level of LDL B protein in the presence of a normal LDL cholesterol level (low LDL sterol to LDL B ratio). For both LDL sterol and LDL B, a polygenic model showed a slightly greater improvement in ln likelihood than did the Mendelian single locus model when both were compared to a sporadic model. Similar results were obtained for sterol levels of high density (alpha) lipoprotein (HDL) sterol. When segregation analysis was performed using the ratio of LDL sterol to LDL B, the Mendelian single locus model gave a slightly better fit to the data than did the polygenic model. While the analyses presented here provided unequivocal evidence for the recessive phenotype of phytosterolemia, we also identified a possible single gene factor that could account for the major portion of the strong familial aggregation in the ratio of LDL sterol to LDL B, and to a lesser extent LDL B. However, there is clear evidence of familial aggregation for these traits in this pedigree beyond that due to Mendelian components.
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PMID:Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia. 370

A 23-year-old man with homozygous familial hypercholesterolemia was found to have coronary ectasia by coronary angiography. This case showed generalized xanthomatosis and severe hyper low density lipoproteinemia, and his cultured skin fibroblasts showed LDL receptor activities compatible with the receptor-defective homozygous type of familial hypercholesterolemia. Coronary angiography showed fusiform aneurysmal involvements in the right coronary artery and left circumflex artery, and 50% stenosis in the right coronary artery and left anterior descending artery. Thus, homozygous familial hypercholesterolemia produces coronary ectasia as well as premature coronary stenosis.
Atherosclerosis 1986 Jan
PMID:Coronary ectasia in a homozygous patient with familial hypercholesterolemia. 394 22

In order to study the relationships between serum lipoprotein lipid concentrations and the concentrations of apo E in serum and interstitial fluid, we have developed a specific, sensitive and rapid radioimmunoassay for this apolipoprotein. Studies of the interstitial fluid lipoproteins and of the gradient between the lipoprotein concentrations in interstitial fluid and serum may add to our understanding of the development of atherosclerosis and xanthomatosis. Serum, interstitial fluid, lipoproteins or standards were incubated with 125I-labelled apo E and rabbit antiserum against apo E for 90-120 min at room temperature. The immune complexes were harvested with the use of formalin-treated staphylococci. The displacement curves produced by standard and samples of serum, interstitial fluid and isolated lipoproteins were linear in logit-log plots and had identical slopes. Delipidation did not change the results and the recovery of added apo E to a serum sample was 96 +/- 5% (n = 5). Apo E was found in all major lipoprotein classes and the concentrations of apo E in serum and in interstitial fluid were 36 +/- 19 mg/l and 8 +/- 4 mg/l, respectively, in normals (n = 21) and 305 +/- 125 mg/ml and 20 +/- 9 mg/l, respectively, in patients with HLP type III (n = 11). Highly significant positive correlations were found in HLP type III between the interstitial fluid level of apo E and the corresponding concentrations of cholesterol and triglyceride. Interstitial fluid apo E concentrations were significantly correlated to apo E but not to the lipid levels in serum, indicating that only some subclasses of the serum lipoproteins are transported to the interstitial compartment.
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PMID:Serum and interstitial fluid apolipoprotein E levels in the healthy and in hyperlipoproteinemia type III as studied by radioimmunoassay. 404 71


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