Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent results regarding the pathophysiology of hyperlipoproteinemia in cholestasis are reported. The isolation of an abnormal lipoprotein (Lipoprotein-X; LP-X) from the plasma of cholestatic patients was achieved by a combination of various physico-chemical techniques. Most of the plasmacholesterol in these patients is transported in form of this abnormal lipoprotein which is very rich in phospholipids and unesterfied cholesterol. LP-X represents a vesicle with a mean diameter of 700 A. Albumin takes part as a structural protein of the particle. Besides albumin, which seems to be located in an internal water compartment or to be covered with lipids. Apo-C and Apo-D are present as surface proteins. The lack of Apo-B in LP-X, the major apoprotein of normal low density lipoproteins, seems to be the reason for a disturbed endogenous feedback mechanism of hepatic cholesterol synthesis, which is strongly increased in cholestasis. The high specificity and power of the LP-X test as clinical-chemical parameter to demonstrate or exclude cholestasis finds its explanation in our knowledge about the origin of this abnormal lipoprotein in cholestasis. LP-X is formed when a lipoprotein normally excreted with the bile refluxes into the plasma stream to convert into LP-X. This formation depends only on certain physico-chemical requirements and is independent of an energy-providing or enzymatically regulated process. The biological halflife of LP-X is similar to that of normal plasmalipoproteins. However, enzymes of postheparin plasma as well as the lecithin: cholesterol acyltransferase do not seem to play a major role in the catabolism of lipoprotein-X, but only change some of the physicochemical characteristics of this vesicle.
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PMID:[Studies on the structure and metabolism of lipoprotein-X (LP-X), the abnormal plasmalipoprotein in cholestasis (author's transl)]. 19 98

Plasma lipoproteins were compared before and after surgical induction of extrahepatic biliary obstruction in dogs by immunochemical techniques, zonal ultracentrifugation and gel filtration. A considerable increase in LDL was found one week after operation, with a zonal ultracentrifugal pattern which was more complex than that found before operation. The lipid composition was characterized by an increase of phospholipids and a decrease of triglycerides in cholestatic LDL fractions. None of the fractions displayed the inverse cholesterol-cholesterol ester ratio, characteristic for human LP-X. The apoprotein composition of cholestatic LDL was also markedly changed. Apoprotein A I, already present in the normal LDL2 subclass, increased and two apoproteins with apparent molecular weight of 35000-40000 appeared in considerable amounts. The amount of HDL was decreased during cholestasis without any appreciable changes in composition.
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PMID:Plasma lipoprotein changes in experimental cholestasis in the dog. 19 65

High density lipoproteins (HDL) of plasma from patients with long-standing cholestasis were studied by several methods including crossed immunoelectrophoresis, gel filtration, and zonal ultracentrifugation. The crossed immunoelectrophoretic pattern against anti-HDL was characterized by the presence of several immunoprecipitates, in striking contrast to the pattern formed by normal HDL. One of these precipitates corresponded to a lipoprotein species dominated by apoprotein A-II (apo A-II). Zonal ultracentrifugation of cholestatic plasma showed a decrease of HDL and a disappearance of the normal delineation of HDL2 and HDL3. In addition a new component designated HDL1-C was observed. Consistent results were found at studies of the molecular size distribution of cholestatic HDL by gel filtration on Sephadex G-200. The lipid and apoprotein composition of isolated cholestatic HDL fractions differed considerably from normal. Most notable were the high proportions of phospholipids and free cholesterol and the occurrence of the apoprotein E (arginine-rich protein) in remarkably high amounts especially in the abnormal HDL1-C.
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PMID:Characterization of high density lipoproteins in human cholestasis. 20 13

An additional cholestatic lipoprotein with a slower mobility than the usual alpha-lipoprotein on polyacrylamide-gel disc-electrophoresis was found in the serum of patients with cholestasis. This abnormal lipoprotein was referred to as Slwo-migrating HDL (HDL-S), because it was mostly recovered in the high density lipoprotein (HDL) fraction after preparative ultracentrifugation. HDL-S was precipitated by dextran sulfate and Mg++ but did not react with either concanavalin A or anti-beta-lipoprotein serum. The main apoprotein of HDL-S was Apo A-I, and a trace of Apo E was also present. HDL-S was relatively enriched in free cholesterol and triglycerides and had a density in the range of 1.063 to 1.083. The appearance of HDL-S in serum or plasma was closely associated with chronic mild intrahepatic cholestasis, particularly as in primary biliary cirrhosis and related conditions.
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PMID:Lipoprotein abnormalities in cholestasis. II. Isolation, characterization and clinical evaluation of an additional cholestatic lipoprotein (slow-migrating HDL). 22 95

The plasma lipoproteins in normal and cholestatic pigs were isolated by zonal ultracentrifugation and studied with respect to apoprotein and lipid composition. In contrast with the distribution in human plasma, only one HDL-population but two LDL-populations were demonstrated. No cholestatic lipoprotein similar to the human lipoprotein X was observed. HDL and the lighter LDL component were largely unchanged in cholestasis. The immunochemical properties were changed to some extent. Thus HDL-reacting material was found in the heavier LDL-component and VLDL after cholestasis but not before.
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PMID:Zonal ultracentrifugation of plasma lipoproteins from normal and cholestatic pigs. 24 19

In this study we have demonstrated that in native bile, lipids are organized in the form of a lipoprotein (bile LP) carrying albumin as apoprotein. The lipid composition of bile LP is almost identical to lipoprotein-X (LP-X, the characteristic lipoprotein of cholestasis). However, it differs from LP-X inits protein/lipid ratio and immunological and electrophoretic characteristics. Bile lipoprotein can be converted into "LP-X-like" material in vitro by adding albumin or serum to native bile. The LP-X-like material formed in vitro has physicochemical and chemical characteristics similar or identical to LP-X isolated from serum. As bile lipoprotein can be converted into LP-X-like material by the addition of albumin to bile, LP-X can be converted into bile-LP-like particles by adding bile salts to a LP-X-positive serum. Furthermore, experimental connection of the common bile duct to the vena cava is followed after a few hours by the appearance of LP-X-like material in the plasma. These facts taken together strongly suggest that bile LP is a precursor lipoprotein for LP-X and that it refluxes into the plasma pool under cholestatic conditions.
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PMID:Formation of lipoprotein-X. Its relationship to bile compounds. 81 9

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

We describe here a 28-years-male with AIHA and SLE who had lipid and lipoprotein abnormalities during cholestasis induced by PGE1 administration. High free cholesterol level, 792 mg/dl was found in his serum, and markedly elevated, phospholipid level 1,614 mg/dl. But, LCAT activity was within normal range in this case. An agarose gel electrophoresis of lipoproteins showed abnormal bands which were located in slow alpha 2, pre beta and slow beta, and between beta and origin point. Moreover, it was detected formation of Lp-X from serum of the patient. Serum levels of apoprotein B, C-II, C-III, and E were higher, while apoprotein A-I, A-II were very lower than reference value. From these results, it was suspected that the patient might occur transient abnormal lipid metabolism according to the drug induced hepatic injury.
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PMID:[A case of systemic lupus erythematosus showing abnormal lipoproteins due to accompanied drug induced hepatitis]. 232 24

Vesicular lipoproteins (e.g., lipoprotein-X) are found in plasma in cholestasis or following infusion of Intralipid or phospholipid. To investigate the metabolism of vesicular lipoproteins, we isolated them from the plasma of subjects with cholestasis or following chronic or single Intralipid infusion. Cholestasis and chronic Intralipid therapy were found to be associated with elevated plasma concentrations of apoE, as determined by radioimmunoassay. Vesicular lipoproteins purified from each of the three types of plasma contained apoE, as well as other proteins. In cholestasis, in which levels of apoE were up to five times normal, a major portion of the plasma apoE was on vesicular lipoproteins. Normalized for apoE content, all preparations of vesicular lipoproteins displaced 125I-labeled LDL from apoB,E receptors of cultured fibroblasts identically. This displacement was inhibited by monoclonal antibodies that block receptor binding of apoE. Vesicular lipoproteins containing 125I-labeled apoE were internalized and degraded by fibroblasts. Different preparations caused small losses or gains of cellular cholesterol, with appropriate stimulation or suppression of apoB,E receptors. Thus, vesicular lipoproteins contain apoE, and apoE mediates their interaction with the apoB,E receptor. Our results suggest that the catabolism of cholesterol-rich vesicular lipoproteins, formed during cholestasis or following infusions of Intralipid or phospholipid, may be receptor-mediated.
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PMID:Recognition of vesicular lipoproteins by the apolipoprotein B,E receptor of cultured fibroblasts. 302 87

An elderly woman with Hodgkin's disease and hepatic involvement but without cholestasis presented with markedly depressed levels of serum esterified cholesterol and high density lipoproteins (HDL). Within five days of her first cycle of chemotherapy her serum HDL-cholesterol rose from 8-10 mg/dl to 88 mg/dl, and levels of the major HDL-apoprotein, apoA-I, rose from 60 to 138 mg/dl. The proportion of unesterified serum cholesterol fell from 60-80% to 27-30%. These observations suggest a relatively specific effect of the hepatic lymphoma on synthesis or release of lecithin:cholesterol acyltransferase.
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PMID:Reversible deficiency of serum high density lipoproteins in Hodgkin's disease. 376 60


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