Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.
 ...
PMID:Hepatic cholesterol ester hydrolase in human liver disease. 68 May 3

Stokke has described a lysosomal cholesterol ester hydrolase (CEH) in human liver. To clarify the significance of this enzyme, we first modified Stokke's assay to enable CEH determination in hepatic needle biopsies. Studies established optimal pH of 4.6--5.2 and linearity of hydrolysis for at least 12 hours, using homogenates containing about 2 mg liver and radiolabeled cholesterol oleate as substrate. The assay was then applied to patients undergoing percutaneous needle biopsy. Hepatic CEH activity in alcoholic liver disease, obstructive jaundice and a variety of other hepatic disorders was not significantly different from that in histologically normal livers. In patients with acute hepatitis, however, mean CEH activity was more than 3-fold increased (P less than 0.01). Values paralleled SGOT levels, returned to normal as hepatitis resolved, and were unrelated to serum cholesterol levels or to lecithin:cholesterol acyltransferase activity. In contrast to CEH, activity of acid phosphatase, a standard lysosomal marker enzyme, was the same in hepatitic as in normal livers. We conclude that CEH can be assayed in needle biopsies of human liver, that its activity increases in acute hepatitis, and that this is probably not simply due to a nonspecific general increase in lysosmal enzymes.
 ...
PMID:Studies on human hepatic cholesterol ester hydrolase in liver disease. 74 52

Hepatitis was induced in rabbits by a single intraperitoneal injection of D(+)-galactosamine-HCl (750 mg/kg body wt). Plasma lecithin:cholesterol acyltransferase activity fell to 5% and lipid transfer protein activity to 50% of control values 48 hr after injection. Discoid high density lipoprotein began to appear in plasma of treated rabbits 36 hr after injection, along with populations of high density lipoprotein (HDL) which were both smaller (radius 3.7 nm) and larger (radius 5.9 nm) than the original HDL population (radius 4.8 nm).
 ...
PMID:D-galactosamine induced hepatitis in the rabbit: effect on lecithin:cholesterol acyltransferase activity, plasma lipid transfer protein activity and high density lipoproteins. 379 65

The apoprotein and lipid composition and the morphology of lipoproteins was determined in rats with D-(+)-galactosamine (GalN) hepatitis. Single intraperitoneal injections of GalN at several dose levels and postinjection exsanguination times resulted in depressed levels of cholesteryl esters, an index of plasma lecithin:cholesterol acyltransferase (LCAT) activity, and increased levels of phospholipids, unesterified cholesterol, and triglycerides. Plasma withdrawn from rats 24 hr after injection of 1000 mg/kg GalN was most deficient in cholesteryl ester and was studied further by sequential isolation of VLDL, LDL, HDL1, HDL2, and HDL3. The increased plasma triglyceride (TG) after GalN treatment accumulated in TG-rich VLDL which contained two types of particles: a large (mean diameter 193.6 +/- 48.3 nm) and rough-edged particle, and a smooth one with a mean diameter (63.4 +/- 13.2 nm) similar to control VLDL (69.4 +/- 20.2 nm). The increased phospholiThe increased plasma triglyceride (TG) after GalN treatment accumulated in TG-rich VLDL which contained two types of particles: a large (mean diameter 193.6 +/- 48.3 nm) and rough-edged particle, and a smooth one with a mean diameter (63.4 +/- 13.2 nm) similar to control VLDL (69.4 +/- 20.2 nm). The increased phospholiThe increased plasma triglyceride (TG) after GalN treatment accumulated in TG-rich VLDL which contained two types of particles: a large (mean diameter 193.6 +/- 48.3 nm) and rough-edged particle, and a smooth one with a mean diameter (63.4 +/- 13.2 nm) similar to control VLDL (69.4 +/- 20.2 nm). The increased phospholipids and unesterified cholesterol were predominantly in LDL, HDL1, and HDL2 which were largely rouleaux of flattened vesicles. Density gradient ultracentrifugation of d greater than 1.006 g/ml lipoproteins confirmed these results. GalN hepatitis appeared to decrease the larger apoB335K subspecies and the apoC-III0 and apoC-III2 content of VLDL. However, total apoB concentration as GalN VLDL was increased 2.6-fold over control. LDL and HDL were markedly enriched in apoE. LDL apoB concentration was decreased by 41% while HDL was deficient in apoA-I, A-II and A-IV, and C. These results demonstrate association of increased plasma triglycerides with particles of grossly abnormal apoprotein composition, and the association of increased plasma phospholipids and unesterified cholesterol with apoE-rich lipoproteins during the LCAT defect produced by GalN hepatitis. These abnormal lipoproteins may represent an abnormal level of normal LCAT substrates important in the transport and esterification of plasma cholesterol.
 ...
PMID:Alterations in lipoprotein composition associated with galactosamine-induced rat liver injury. 711 68