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)

Activities of organelle specific enzymes (succinate dehydrogenase, glucose-6-phosphatase, acidic DNAase, acidic RNAase, acidic and alkaline phosphatases) were measured in homogenates and subcellular fractions of liver tissue of patients with cholelithic disease. Liver tissue samples analyzed were investigated also by light and electron microscopy. The data obtained were considered in connection with localization of cholelith in biliary system, type of inflammation, presence of subhepatic cholestasis and of accompanying syndrome of pancreatitis. Typical alterations were observed in the activity of organelle specific enzymes and in the ultrastructure of mitochindria, lysosomes and endoplasmic reticulum in cholelithic disease. The most distinct alterations in the enzymatic activities were found in choledocholithiasis as well as in subhepatic jaundice.
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PMID:[Changes in organelle-specific enzyme activity and the ultrastructure of liver cells in cholelithiasis]. 19 99

Since the introduction of oral contraceptive steroids in 1960 there has been a sharp increase in the incidence of benign liver tumors. Epidemiologic and other evidence links focal nodular hyperplasia and hepatic cell adenoma to the use of these agents. The risk increases with long-term exposure. The majority of patients were less than 35 years old. Most patients were exposed to mestranol (ME) alone or alternately with ethinylestradiol, both synthetic steroidal estrogens. Inability to demethylate ME in the smooth endoplasmic reticulum of hepatocytes may allow massive accumulation of oncogenic metabolites. This is probably a pharmacogenetic variable in a small number of women. Cholestasis, hypervascularity, induction of intracellular enzyme systems, thrombogenesis, and thickening of arterial and venous walls are other known effects of synthetic estrogens and progestogens. All may contribute to the pathogenesis of liver tumors. Many patients are asymptomatic until there is rapid expansion of the tumor. Pain occurs when Glisson's capsule stretches. Intrahepatic bleeding and liver rupture are common sequelae. Ligation of the hepatic artery may be lifesaving in the face of exsanguinating liver bleeding. Reports of regression with observation alone are encouraging. Instances of progression of unresected adenomas to rupture during subsequent pregnancy dictate avoidance of sex steroids in patients with hepatic neoplasia. Sonography, computerized axial tomography, radionuclide scans, and selective celiohepatic angiography are useful methods for the diagnosis of liver tumor in the symptomatic patient. There is a primary need to develop biochemical methods for detecting patients at risk for developing liver tumors. Epidemiologic research and central reporting of case histories are needed in the search for common factors.
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PMID:Role of oral contraceptive agents in the pathogenesis of liver tumors. 22 97

The enzyme gamma-glutamyl transpeptidase is widely distributed throughout the body, notably kidney, seminal vesicles, pancreas, liver, spleen and brain. Being one of the enzymes of the gamma-glutamyl cycle, it is involved in aminoacid transport, catalysing a transpeptidation reaction between gamma-glutamyl peptides and most common amino acids. Methods of assay of the enzyme are based on its ability also to act on synthetic amides of glutamic acid; kinetic methods monitoring the release of p-nitroaniline from the substrate L-gamma-glutamyl p-nitroanilide are the most satisfactory. In diseases of the liver, the highest levels occur in association with cirrhosis, alcoholism, hepatic secondaries and cholestasis. As the enzyme is present in the endoplasmic reticulum of the hepatocyte, its activity is increased in situations leading to microsomal enzyme induction. Raised levels can also occur in pancreatitis, diabetes, myocardial infarction, congestive cardiac failure, chronic renal failure, cerebrovascular accidents, cerebral tumours and chronic obstructive pulmonary disease. Although the lack of specificity must be recognised, the estimation can be useful in the elucidation of some clearly defined problems arising during investigation of patients with suspected hepatic disease, especially where performed as part of a biochemical profile.
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PMID:Role of gamma-glutamyl transpeptidase activity in the diagnosis of hepatobiliary disease. 24 76

The major abnormal plasma lipoprotein of cholestasis (LP-X) was isolated from blood plasma and from perfusates of isolated livers of rats with biliary obstruction. In both cases LP-X was composed mainly of about equimolar parts of phospholipids and unesterified cholesterol; the small protein component was primarily the arginine-rich apolipoprotein. By electron microscopy, LP-X appeared as a unilamellar liposome (690 A mean diameter, range 400-1000 A) with the trilaminar staining image typical of phospholipid bilayers. Extensive block staining of cholestatic livers for 48 hr with warmed uranyl acetate (37 degrees) permitted the visualization of vesicles indistinguishable from LP-X within hepatic parenchyma. These trilaminar-staining vesicles occurred predominantly within bile canaliculi. They also were seen in nearby cytoplasmic vacuoles or invaginations between hepatocytes and in the space of Disse. Similar vesicles were not seen in the endoplasmic reticulum or Golgi cisternae. These observations raise the possibility that the vesicles are formed within bile canaliculi and are transported from the canaliculi to the space of Disse within pinocytotic vacuoles.
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PMID:Secretion of lipoprotein-X by perfused livers of rats with cholestasis. 27 47

The investigations on experimental intrahepatic cholestasis of the last 10 years suggest that any of several different functional alterations may lead to cholestasis. In most studies very high doses of cholestatic compounds have been used. The relevance of these studies to clinical syndroms of cholestasis which usually are observed at much lower doses, is unclear. One target of cholestatic compounds may be the lipid phase of several cell structures such as the sinusoidal and canalicular membrane, the endoplasmic reticulum and the mitochondria. By their capacity to interact with the lipid layer and proteins of membranes these compounds impair specific cellular functions: the activity of carrier proteins, the activity of the hydroxylating system and the energy supply. Another target may be the binding proteins in the cytoplasma and possibly the microfilaments. One may suggest that other factors such as interference with regulatory processes in the cell may be of interest in the future. So far the primary event of drug-induced intrahepatic cholestasis is still unknown and it is not even clear whether the increased bile acid levels are cause or consequence of the cholestatic condition.
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PMID:Current concepts in intrahepatic cholestasis. 32 28

To show what damage occurs in the hepatocytes of psoriatics receiving Methotrexate (MTX) therapy liver biopsies from 24 psoriatics with severe psoriasis before and after MTX therapy were studied blind by light and electron microscopy. We also aimed to determine the severity of lesions and find possible correlations, and to seek a relationship of these observations with light microscopical and clinical findings. The present study has shown that MTX probably caused damage to the hepatocytes reflected in the membrane whorls (p less than 0.05) and the accumulation of lipid droplets (p less than 0.05). There was an increase (p less than 0.05) in autophagic vacuoles, which mostly contained glycogen and cell sap with residual bodies. These residual bodies were then found in an increased number in the nearby Kupffer cells. Crystals were found in megamitochondria in most patients before and after MTX therapy. Some of these crystals were found free in the cytoplasm. Mitochondria containing crystals were shown in autophagic vacoules, representing possible pathways of their breakdown. Bile canaliculi commonly contained debris but only one patient had evidence of cholestasis. There was no significant change in nuclei, Golgi apparatus, or the endoplasmic reticulum and no statistically significant correlation between the shown changes and the total dose of MTX given.
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PMID:Liver ultrastructure in psoriatics related to methotrexate therapy. 1. A prospective study of findings in hepatocytes from 24 patients before and after methotrexate treatment. 60 66

A quantitative analysis of needle liver biopsies of patients with untreated, uncomplicated cholelithiasis has been performed to better evaluate eventual changes occurring under medical therapy of gallstones. With the light microscope, the intensity of parenchymal steatosis was variable among the patients but the mean volume density of lipid droplets was significantly increased as compared to normal subjects. In addition, there was a significant increase in the volume density of lipocytes (fat-storing cells) without an increase in the number per square area, suggesting a hypertrophy of individual cells. The data obtained by ultrastructural morphometry show a significant increase in the surface density of the rough endoplasmic reticulum in the hepatocytes, a significant increase of the mitochondrial volume density together with the presence of curled mitochondrial cristae and a slight, inconstant intracellular and intracanalicular bile retention. No qualitative or quantitative changes were observed at the level of the smooth endoplasmic reticulum. The activity of the microsomal enzyme NADPH-cytochrome c reductase as evaluated on liver biopsy material was in the normal range. Some of the features observed in this group of patients are reminiscent of alterations previously described in human or experimental cholestasis and suggest that they might depend on a common underlying disturbance in cholesterol and bile salt metabolism.
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PMID:A stereological and biochemical study of the human liver in uncomplicated cholelithiasis. 73 37

A ten-year-old boy persented with a prolonged cholestatic liver disease 5 weeks after starting diphenylhydantoin therapy. The initial phase of his illness was characterized by hepatocellular damage with swollen liver cells and centrilobular cholestasis. Severe hyperlipoproteinemia with eruptive xanthomata developed within 3 weeks of his initial jaundice. The second phase of his illness was characterized by portal tract inflammation with bile ductular proliferation and chronic cholestasis gradually resolving over a period of 15 months. It is postulated that diphenylhydantoin sensitivity produced swollen hepatocytes with hypertrophy of the smooth endoplasmic reticulum, reducing hepatic sinusoidal blood flow and the clearance of secondary bile salts. A fall in clearance of lipoproteins, including the cholesterol precursor of primary bile acid synthesis, may have been responsible for a reduction in serum bile acid concentration. High levels of serum lithocholic acid, largely unsulfated presumably due to decreased hepatic uptake, may have produced the prolonged second phase of this illness when histological changes resembled that seen in experimental animals following lithocholic acid administration.
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PMID:Cholestatic liver disease associated with diphenylhydantoin therapy. Possible pathogenic importance of altered bile salt metabolism. 84 35

Patients with a metabolic block in the conversion of THCA into cholic acid develop cirrhosis and hemolysis, and die of hepatic failure. In these patients, THCA is largely conjugated to taurine (tauro-THCA) and excreted instead of being converted into cholic acid. In the present study, the effects of tauro-THCA on hemolysis, bile flow, and hepatic morphology were evaluated in bile fistula rats. All rats infused with tauro-THCA at rates of 0.25, 0.50 or 0.75 micronmol/min developed hemolysis with hemoglobinuria. A direct toxic effect of tauro-THCA on washed human red blood cell membranes was demonstrated at a concentration of 8 X 10(-4) M. Liver biopsy sections from rats infused for a 2 hr period with tauro-THCA were examined by electron microscopy and showed dilation of the rough endoplasmic reticulum and distortion of mitochondrial membranes. Cholestasis was not induced, since tauro-THCA actually caused a greater choleretic response for a given rate of bile salt excretion than did taurocholate. This study raises the possibility that the clinical liver disease seen in patients with a metabolic block in the conversion of THCA into cholic acid may be caused by tauro-THCA.
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PMID:Hepatic lesions and hemolysis following administration of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oyl taurine to rats. 89 5

Electron microscopic findings of the liver are being described found in 4 patients aged from 12 months to 26 years after poisoning with Amanita phalloides. Marked alterations were seen in nuclei, in the endoplasmic reticulum, and in mitochondria. Morphologic criteria of cholestasis were observed in one patient. Extreme cellular edema was found in two patients. Since our findings differ considerably in several points from those patients with Amanita phalloides poisoning previously reported, one may suppose, that e.g. age, sex, preexisting damage and liver function might be highly important for the extent and form of resulting liver damage.
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PMID:[Electron miscoscopy studies of liver tissue in patients with amanita phalloides poisoning]. 101 71


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