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)

17 alpha-Ethynyl estradiol-induced cholestasis was used to study the relationship of protein to bile salt transport in liver. The biliary secretion of horseradish peroxidase was unaltered in treated animals despite a 56% reduction in bile flow. Cytochemistry confirmed that estradiol caused no alteration in the handling of tracer. In a second study, the peak biliary secretion of [14C]taurocholate was reduced by approximately 46% in treated animals. The kinetics of 125I-cholyglycylhistamine, a bile salt derivative, were identical to those of taurocholate in control and cholestatic animals. Taurocholate and cholylglycylhistamine secretion were markedly reduced in control animals during competition with unlabeled taurocholate. Quantitative electron microscopic autoradiography with 125I-cholylglycylhistamine revealed a high concentration of grains over the endoplasmic reticulum and the Golgi complex including associated lysosomes and vesicles. These data demonstrate that estradiol markedly inhibits bile salt transport, but not vesicular transport of horseradish peroxidase. Furthermore, estradiol may alter the movement of bile salts through these organelles.
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PMID:Hepatic handling of bile salts and protein in the rat during intrahepatic cholestasis. 683 71

The authors report the case of a patient with ajmaline hepatitis. The clinical presentation suggested angiocholitis; serum bilirubin concentration and the activity of alkaline phosphatase were markedly increased; serum transaminase activity was moderately increased; the prothrombin time remained normal. After interruption of the drug, the outcome was favorable, with complete recovery within 2 months. Histologic examination of a liver specimen obtained early after the onset of jaundice showed inflammatory cells in the portal tracts and mild hepatocytic lesions. Electron microscopy disclosed dilatation of the endoplasmic reticulum. The microfilamentous network of the hepatocytes was reduced and disorganized. Biliary canaliculi were enlarged with absent or blunted microvilli. There was evidence for passage of bile products from the biliary caniculi into the space of Disse. These aspects are reminiscent of those observed in animals after the administration of cytochalasin B. It is suggested that ajmaline may, in some patients, trigger an immune response which then alters the microfilamentous network of the hepatocytes, and may, thereby, produce cholestasis.
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PMID:[Ajmaline-induced hepatitis. A case report with ultrastructural study]. 687 68

Cytotoxic effect of excessive copper in the liver of the dogs with longstanding obstructive jaundice were investigated. Common bile duct was ligated in adult mongrel dogs for a period of 21 to 93 days. Copper (0.5 mg/kg weight, every other day) was administered intravenously. Copper content and morphologic changes of the liver was compared with those of the common bile duct ligated dogs without copper administration and of the normal control. Liver copper content was quantitated by atomic absorption spectrophotometry and morphologic investigation was carried out ultrastructurally and histochemically (dimethylaminobenzylidine rhodanine stain for copper and orcein stain for copper associated protein). The copper content of the liver was 57 +/- 8.75 microgram/g wet weight (mean +/- S.E.) in the normal control, 80.84 +/- 15.76 in the common bile duct ligated dogs and 463.46 +/- 76.42 in the common bile duct ligated dogs with copper administration. There was a significant increase (p less than 0.01) of the liver copper content in the common bile duct ligated dogs with copper administration but not in the common bile duct ligated dogs without it. Histologically, the liver showed changes of longstanding cholestasis and of early biliary cirrhosis in the dogs over three months after ligation. Ultrastructurally, both groups showed dilatation of bile canaliculi with decreased and swollen microvilli protruding into their lumina, expanded pericanalicular ectoplasm with increased microfibrils and various forms of intracanalicular and intracytoplasmic bile assuming myelin-figure, crystalloid and dense-amorphous appearances. Also present were increased and dilated smooth-surfaced endoplasmic reticulum, mitochondria showing curled cristae with electron dense ground substance and decreased microvillous projections of hepatocyte cell membranes into Disse's space. Only significant morphologic difference between two groups was the presence of copper-protein complex demonstrated by rhodanine and orcein stains as intracytoplasmic coarse granules in the common bile duct ligated dogs with copper administration. These copper-protein complex granules correspond to partially membrane-bound dense bodies seen ultrastructurally, which probably represent autophagic vacuoles or lysosomal residual bodies. Above result suggests that excessive copper accumulated in the liver as lysosomal bodies in longstanding extrahepatic biliary obstruction with copper loading does not produce significant liver cell injury despite eight fold increase of the liver copper content.
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PMID:Copper and liver injury--experimental studies on the dogs with biliary obstruction and copper loading. 712 50

Thirteen patients (9 women, 4 men) with solitary (7) or multiple (6) radiolucent gallstones were treated with 1.0 g/day CDCA over a period of 7--17 months (mean 10.2). Routine liver function tests showed no changes compared to pre-treatment values, except a moderate elevation of SGPT activity in one patient. Serum cholesterol and serum triglyceride levels remained unchanged during therapy. 21 liver biopsies in 11 patients compared to pre-treatment controls studied by light and electron microscopy revealed no lesions in hepatic structure, especially no signs of cholestasis. Only some unspecific changes in liver ultrastructure as shown during therapy with other drugs developed during CDCA treatment (lipofuscin depositions, swollen and condensed mitochondria and a dilated rough endoplasmic reticulum). It is, therefore, concluded that CDCA therapy for gallstone dissolution has no hepatotoxic side effects.
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PMID:Light and electron microscopy of human liver before and during chenodeoxycholic acid therapy. 721 31

Alterations of cellular membranes under the influence of bile acids seem to be of pathophysiological importance in cholestasis. The effect of taurolithocholic acid (TLCA) and chenodeoxycholic acid (CDCA) on membrane structure and release of cellular enzymes was studied on isolated rat hepatocytes. The response of urea synthesis to glucagon was used as a parameter of membrane function. The threshold dose of TLCA, marked by rapidly increasing enzyme release, was about 100 micrometers, whereas that of CDCA was between 500 and 1,000 micrometers. Addition of albumin (1 g-%) increased the threshold dose of CDCA; this occurred for TLCA only 8 g-%. Electron-microscopical alterations of the endoplasmic reticulum and submembranous areas were found with concentrations below these threshold doses even in the presence of albumin. These alterations are interpreted as disturbance of cellular transport and energy metabolism. TLCA inhibited glucagon response of cells in concentrations below 100 micrometers. These results demonstrate an influence of the bile acids studied on structure and function of liver cell membranes, which may be of importance in the pathogenesis of cholestasis. The rough endoplasmic reticulum could be another cellular structure which is affected by these bile acids.
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PMID:[Different effect of taurolithocholate and chenodeoxycholate on structure and function of isolated hepatocytes (author's transl)]. 725 40

Alkaline phosphatase isoenzymes (API) in serum of rats during cholestasis are investigated. For comparison different membrane systems in liver are damaged. Proliferation of bile canaliculi, sinusoidal area, and endoplasmic reticulum, respectively, is induced by different toxic conditions. It is found that in cholestasis an API5 in serum arises which is not present in serum of normal rats, but can be detected in normal rat liver. Thus, it is not a de novo synthesis of this API. Under the condition connected with a proliferation of bile canaliculi we find this API5 in serum. Under different conditions without proliferation of bile canaliculi we do not find an increase of this API5. We assume, therefore, that API5 in cholestasis is produced by cells of the bile canaliculi rather than by liver parenchymal cells in the sinusoidal area. No difference is found in intra- or extrahepatic cholestasis.
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PMID:Alkaline phosphatase isoenzymes in serum of rats during cholestasis. 732 57

The behaviour of cytomembranes of the smooth endoplasmic reticulum (SEP) in the hepatic cells was observed with a special reference to their dependence on bilirubin. Basing on the author's observations and comparing them with the data of the literature, it was possible to conclude that the peculiar formations in the ESR of the liver at cholestasis should be considered as an adaptive demonstration of the hepatic cell to changes occurring in biliary secretion. From morphological point of view, a special variant of the SER cytomembranes, known as glycogenic bodies (GB), is an equivalent to massive cholestasis, and from biochemical point of view (that is more probable) it demonstrates transmission to a reserved metabolic way connecting with the production of glucuronic acid.
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PMID:[Unusual endoplasmic reticulum formation in liver cells during cholestasis]. 738 16

Liver specimens obtained immediately after death from eight severely malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who had recovered from malnutrition. The liver cells from the fatal cases showed mitochondrial swelling, with coarse densities in the matrix, cholestasis, depletion of the endoplasmic reticulum and Golgi apparatus, diminished glycogen stores, prominent lipid deposits and focal cytoplasmic degradation. The nucleoli were enlarged. There was marked reduction in peroxisomes. In contrast, the biopsies from recovering children showed good cellular organisation, and a normal frequency of peroxisomes. Multiple factors, including sepsis, may lead to depletion of peroxisomes. Loss of peroxisomes may interrupt beta-oxidation of long-chain fatty acids and accentuate the accumulation of lipid. Moreover, a reduction in the concentration of catalase may remove one avenue for the detoxification of free radicals. As the concentration of other anti-oxidants, notably glutathione, is also reduced, free radical damage may occur, leading to lipid peroxidation of membranes, mitochondrial damage, pump failure and influx of water and electrolytes into the cell.
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PMID:Peroxisomes and the hepatic pathology of childhood malnutrition. 803 10

1. alpha 1-antitrypsin is an antiprotease that inhibits the neutrophil elastase enzyme, and belongs to a family of structurally related serine proteinase inhibitors (serpins). Its methionine358 residue determines the specificity for elastase. 2. The normal M-type alpha 1-antitrypsin is mainly synthesized in the liver parenchymal cells and transported to the plasma. Abnormal Z-mutant alpha 1-antitrypsin is retained in the endoplasmic reticulum, which leads to its intracellular accumulation and to markedly decreased plasma levels. 3. In normal conditions, alpha 1-antitrypsin protects the lungs from destruction by the proteolytic neutrophil elastase. A protease/antiprotease imbalance in the lung is responsible for the development of emphysema in severe alpha 1-antitrypsin deficiency and in cigarette smokers, and accounts for the marked acceleration of the lung disease in smoking alpha 1-antitrypsin deficient patients. Smoking has to be avoided in alpha 1-antitrypsin deficient patients. Replacement therapy with plasma-derived alpha 1-antitrypsin seems indicated in alpha 1-antitrypsin deficient patients with emphysema. 4. Intracellular accumulation of abnormal Z-alpha 1-antitrypsin molecules in liver parenchymal cells may lead to liver disease, ranging from neonatal cholestasis to adulthood cirrhosis and hepatocellular carcinoma. End-stage liver disease can be treated by liver transplantation, which is followed by a phenotypic conversion. 5. Diagnosis of alpha 1-antitrypsin deficiency related disease relies on the presence of a low serum concentration of alpha 1-antitrypsin, and of periodic-acid Schiff positive globules in the liver parenchymal cells. Isoelectric focusing of the serum identifies the protease inhibitor phenotype. The protease inhibitor phenotype is determined by the independent expression of the two parental alpha 1-antitrypsin alleles. It is determinant of the serum level and of the risk for development of lung or liver disease.
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PMID:Alpha 1-antitrypsin deficiency: an overview. 839 99

Eleven cases of biliary atresia (BA) and eight of neonatal hepatitis (NH) were studied, using transmission electron microscopy, to document their different ultrastructural characteristics and to elucidate the possible pathogenesis of biliary atresia. Among 30 consecutive liver biopsies obtained from 19 infants with BA or NH, 21 specimens composed (13 BA, 8 NH) were examined ultrastructurally. The electron microscopic features of NH (patients' age range, 35 to 60 days) were (1) giant hepatocytic transformation with scattered areas of dilated endoplasmic reticulum, indicative of intracytoplasmic degeneration, (2) frequent cytoplasmic biliary necrosis, and (3) relatively intact microvilli in most bile canaliculi, which contained some hepatocytic cytoplasmic fragments. These features strongly suggest that the main pathological process in NH is hepatocellular injury rather than bile duct damage. In contrast, all cases with BA (age range, 27 to 130 days) demonstrated (1) marked hepatocellular cholestasis associated with many lysosomes and myelin figures, (2) marked loss of bile canalicular microvilli, (3) degenerated bile ductular cells containing bile pigments, and (4) periductal inflammatory fibrosis. These features suggest that the main pathological process in BA involves the biliary system. A few viral inclusions were observed in two cases with BA, which suggests that viral infection is a potential cause. In two BA cases (aged 40 and 43 days at the time of first biopsy), the ultrastructural findings essentially were the same as those of NH, and follow-up biopsy specimens (at 48 and 94 days) showed findings consistent with BA. Such results support Landing's hypothesis that BA and NH are different manifestations of a single pathological process.
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PMID:Electron microscopic study of the liver with biliary atresia and neonatal hepatitis. 870 5


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