Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic diseases differ from most other causes of secondary dyslipidaemia in that the circulating lipoproteins are not only present in abnormal amounts but they frequently also have abnormal composition, electrophoretic mobility and appearance. Pre-beta and alpha bands can be absent on electrophoresis in all types of liver disease although material in the VLDL and HDL ranges can be isolated in the ultracentrifuge. Cholestatic liver disease has been the most extensively studied and the hyperlipidaemia can be extreme with marked elevations of free cholesterol and phospholipids. This results largely from the presence of LP-X, an abnormal LDL, with a vesicular structure that appears in rouleaux formation under the electron microscope. It is virtually specific for cholestasis and familial LCAT deficiency. The LDL, however, is heterogeneous and may also contain a large triglyceride-rich particle (LP-Y) as well as more normal-looking particles, which are none the less depleted in cholesteryl esters and rich in triglycerides. Indeed, when patients with cholestasis are hypertriglyceridaemic the excess triglyceride is to be found predominantly in these two LDL fractions rather than in VLDL. HDL in cholestasis may contain disc-like particles, similar to those newly secreted by the liver and intestine, as well as more normal-looking spherical particles. In extrahepatic obstruction concentrations of HDL and its major apolipoproteins, apoAI and apoAII, are frequently reduced, although a subfraction rich in apoE is often found. In all but the latest stages of chronic intrahepatic cholestasis due to primary biliary cirrhosis, however, HDL, especially HDL2, concentrations are increased, probably due to the presence of a circulating inhibitor of HL. Many of these lipoprotein changes found in cholestasis resemble those of familial LCAT deficiency, although the hyperlipidaemia is not usually so severe in the latter condition. Indeed, in patients with cholestasis but well-preserved LCAT activity many of the characteristic lipoprotein changes, such as LP-X, LP-Y and discoidal HDL, may not be seen. In acute hepatocellular disease, such as alcoholic or viral hepatitis, it is not unusual for the patient to go through a cholestatic phase and many of the same lipoprotein changes may be seen. In cirrhosis without cholestasis the patients are not usually significantly hyperlipidaemic and in advanced cases cholesterol and apoB levels may be reduced. Although LCAT activity and the proportion of plasma cholesterol esterified may also be markedly reduced, LP-X is not usually seen, possibly because the flux of free cholesterol and phospholipid (lecithin), the LCAT substrates, is relatively low. Discoidal HDLs are often present.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dyslipoproteinaemia of liver disease. 208 7

A ninth Japanese patient afflicted with lecithin-cholesterol acyltransferase (LCAT) deficiency is described with emphasis on renal pathology. The most striking feature is massive deposition of lipid material in the glomeruli, particularly in the glomerular basement membrane (GBM) and in the mesangial region. The glomerular changes appear to be similar to that seen in some cases with cirrhosis of the liver. Lipid material contains a large amount of apolipoprotein-B detected by immunohistology. In two renal biopsies, taken three years apart, renal pathology is essentially the same and glomerular pathology is most characteristic. It is suggested that lipid deposition in glomeruli in this patient is rather slow. Family study of the present case reveals consanguinous marriages in the previous two generations suggesting the exaggerated gene expression of LCAT deficiency in this family.
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PMID:Nephropathy of familial lecithin-cholesterol acyltransferase deficiency: report of a case. 351 May 35

An ultracentrifugal technique for separating and analyzing serum lipoproteins was evaluated in comparison with analyses by electrophoresis using agarose-gel and polyacrylamide-gel. In general, the percent of pre beta- and beta-lipoproteins in electrophoresis was estimated higher than the percent of VLDL and LDL in ultracentrifugal method, while the percentage of alpha-lipoprotein in the former was estimated lower than that of HDL in the latter. In cases with abnormal lipoproteinemias, various discrepancies arose between the methods. For examples, pre beta- and beta-lipoproteins were estimated too high by the analyses with electrophoresis. The cholesterol content in HDL decreases in hypertriglyceridemia accompanied by an increase in triglyceride content. Therefore, when HDL cholesterol is determined by a polyanion method to assess the net HDL concentration in such cases, it is estimated to be low. Such errors are not only found in the determination of HDL cholesterol, but also in apoproteins in liver cirrhosis, because the composition of HDL apoprotein is markedly altered. Since the heterogeneity of lipoproteins separated by ultracentrifugation is characteristic in hereditary disorders of lipoproteins such as LCAT deficiency, the centrifugal technique is essential for lipoprotein analysis in such disorders. The disadvantages in ultracentrifugation are cross-contaminations among fractions, and removals of lipids and apoproteins from lipoprotein particles. Apo A-I and E proteins, and phospholipids were removed from the particles more rapidly than other components. From the results of repeated ultracentrifugation of HDL, 3% of apo A-I was estimated to be lost from the HDL during the centrifuge procedure.
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PMID:[Evaluation and problems of ultracentrifugal technique for separation and analysis of serum lipoproteins: comparison with other analytical methods]. 836 Oct 44