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)

Plasma cholesterol esters are formed within the circulation by lecithin-cholesterol acyltransferase (LCAT), an enzyme produced by the liver. Patients with hepatocellular disease have low plasma LCAT activity. This largely accounts for the decreased levels of cholesterol esters observed in such patients and appears due to impaired hepatic production of the enzyme. In contrast, activity of the LCAT reaction in patients with cholestasis seems variable and is the subject of controversy, largely because the influence of abnormal cholestatic lipoproteins on the reaction requires further clarification.Human liver contains a lysosomal cholesterol ester hydrolase (CEH) which may play an important role in hepatic cholesterol homeostasis. In patients with liver damage there is no concrete evidence of circulating CEH activity, but recent studies show elevated activity of hydrolase within the liver itself in acute hepatitis. Hepatic activity of another lysosomal enzyme, acid phosphatase, is not increased, suggesting that high CEH in hepatitic liver does not simply reflect a general increase in lysosomal enzymes. The pathogenesis and significance of altered CEH activity in liver disease require further study.
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PMID:Studies on cholesterol ester formation and hydrolysis in liver disease: a selective review. 37 22

Deposits of bile in the cytoplasm of hepatocytes from six patients with cholestasis were studied by electron microscopy and ultrastructural cytochemistry. The deposits were identified in vacuoles of varying size and complexity. The demonstration of acid phosphatase activity in these vacuoles suggests that lysosomes participate in the elimination of bile deposits retained in hepatocytes.
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PMID:Lysosomal degradation of bile deposits in cholestasis. An ultrastructural and cytochemical study. 41 1

Investigations on the high molecular weight isozyme of alkaline phosphatase (R type of AP), which is typically found in the serum of patients with cholestasis, have revealed that AP of the R type corresponds to the conventional liver AP which is attached to vesicular material. The isolation of these vesicles by Sepharose gel filtration is described. Several features were found to be characteristic for these vesicles: 1. The presence of the following enzymes known to be membrane bound: alkaline phosphatase (AP), 5FEET-NUCLEOTIDASE, L-leucyl-beta-naphthylamidase (LAP), and gamma-glutamyl transpeptidase (gamma-GT). 2. The absence of the following enzymes known not to be present on cell membranes: glutamic pyruvic transaminase (SGPT), glutamic oxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), and acid phosphatase. 3. The typical ultrastructural appearance and the cytochemical visualization of alkaline phosphatase and 5feet-nucleotidase. It is concluded that the vesicles correspond to fragments of the liver cell membranes that appear and continue to circulate in the blood of patients with cholestasis.
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PMID:The separation and characterization of liver plasma membrane fragments circulating in the blood of patients with cholestasis. 112 24

Acid phosphatase, alkaline phosphatase and 5'-nucleotidase activities were analyzed cytophotometrically in cryostat sections of rat liver up to 8 weeks after ligation and transsection of the common bile duct. Ligation resulted in cholestasis and induced alterations in both localization and activity of the enzyme investigated. The cellular distribution but not the activity of acid phosphatase changed in liver parenchyma. In control liver, the final reaction product was localized as discrete granules in the bile canalicular region of hepatocytes. The final reaction product was precipitated more diffusely within the cytoplasm after induction of cholestasis, most probably due to increased fragility of lysosomal membranes. In control liver, alkaline phosphatase activity was low and localized in the bile canalicular plasma membranes only. The total parenchymal activity increased threefold after the induction of cholestasis and is considered to be a compensatory mechanism in order to enhance the excretion of bile salts from hepatocytes. 5'-Nucleotidase was present at the bile canalicular and sinusoidal surfaces of plasma membranes of hepatocytes in control liver; total activity in pericentral areas was significantly higher than in periportal areas. Induction of cholestasis resulted in higher total activity and redistribution of the activity over all three surfaces of the plasma membranes, whereas heterogeneity over the different zones of the acinus disappeared. The appearance of the enzyme at lateral plasma membranes is suggested to be related to the formation of new sites for bile salt transport out of the hepatocytes. With respect to all three enzymes studied, alterations of liver parenchymal cells due to a disturbed bile transport were already established during the first week of cholestasis.
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PMID:Quantitative changes in acid phosphatase, alkaline phosphatase and 5'-nucleotidase activity in rat liver after experimentally induced cholestasis. 238 57

Studies of the activity uptake of radiolabelled 99mTc2S7 colloid in different tissues showed a moderately increased uptake in the lung 1 week and a greatly increased uptake 3 weeks after permanent bile duct occlusion. Three weeks after bile duct occlusion the activity uptake was also slightly increased in the spleen and moderately reduced in the liver. In pulmonary tissue of cholestatic rats, the levels of alkaline and acid phosphatase, beta-glucuronidase, and beta-hexosaminidase were determined after 6 weeks. The pulmonary contents of beta-glucuronidase was increased tenfold, and that of beta-hexosaminidase was increased fourfold in cholestasis. Histochemical investigation showed that the lysosomal enzymes were located in the macrophages, which in cholestasis were abundant in alveolar walls and inside alveoli. Macrophages were also frequently seen to engorge pulmonary veins.
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PMID:Radiolabelled colloid uptake distribution and pulmonary contents and localization of lysosomal enzymes in cholestatic rats. 371 95

The effects of colchicine on the mouse gallbladder followed a course depending on the dosage given (0.4-4 mg/100 g body weight). Following 0.5 mg/100 g, by 16 h there was a marked cholestasis with dilatation of the gallbladder and steatosis. There were progressive alterations in the Golgi apparatus and accumulation of vesicles. The apical mucous droplets decreased in number and became pleomorphic and dispersed throughout the cytoplasm. Lipid droplets appeared in numbers on the epithelial cytoplasm. By 48 h the tissues had reverted to normal appearances. When cholecystokinin, pilocarpine or ceruletide were given to animals which had received colchicine 18 h previously, the excess bile from the dilated gallbladder was discharged into the duodenum, remaining apical mucous droplets secreted and electron dense material accumulated in the lateral intercellular space. This formed a quasi-regular array between the epithelial bases and the basement membrane. Biochemically there was a significant decrease in alkaline phosphatase activity and a significant increase in acid phosphatase activity.
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PMID:Effects of colchicine on the gallbladder of the mouse. 373 64

Degeneration of all bile canaliculi takes place in the liver of the sea lamprey, Petromyzon marinus, during metamorphosis. Disintegration of microvilli is observed during earlier stages, and membranous debris ultimately accumulates within the canalicular lumina. Complete occlusion of the lumina and disorganization of junctional complexes is followed by a complete loss of the exocrine biliary pole of hepatocytes and a reorganization of these cells into solid cords. An increase in the size and number of acid phosphatase-containing cytoplasmic bodies coincides with the events of canalicular degeneration. These secondary lysosomes apparently participate in some manner in the isolation and disposal of iron and other bile constituents which no longer can be excreted in bile canaliculi. The loss of the exocrine biliary pole of hepatocytes is concomitant with vascular disturbances in the form of disordered arrangements of sinusoidal endothelial cells and an increase in the population of activated Kupffer cells involved in erythrophagocytosis. The significance of the shift in functional organization of the liver in adult lampreys is discussed in relation to physiological changes in this organism and to human hepatic cholestasis, for which this organism is a potentially valuable experimental model.
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PMID:Morphological changes in the liver of the sea lamprey, Petromyzon marinus L., during metamorphosis. II. Canalicular degeneration and transformation of the hepatocytes. 666 26

We have studied four children (ages 6 to 17 years) with chronic cholestasis who developed a slowly progressive neuromuscular disease characterized by ataxia, dysmetria, areflexia, loss of vibratory sensation, and a variable ophthalmoplegia. Serum vitamin E concentrations were low in all patients prior to treatment (0.17-2.0 mg/g cholesterol, normal greater than 3 mg/g). Muscle histochemical studies showed prominent yellow autofluorescence, basophilic cytoplasmic inclusions which stain with esterase and acid phosphatase, and occasional necrotic fibers. Ultrastructural findings consisted of increased number and size of membrane-bound dense bodies (lysosomes), membranous whorls, and autophagic vacuoles. Intramuscular injections of all-rac-alpha-tocopherol (0.55-1.42 mg/kg per 24 hours based on individualized pharmacokinetic data) were required in three patients to achieve normal serum vitamin E values. High-dose (32 mg/kg per 24 hours) oral supplementation was effective in one patient. After normalization of serum vitamin E concentrations for 12 to 20 months, the neurologic disease has improved in all four patients.
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PMID:Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: clinical and muscle biopsy findings and treatment with alpha-tocopherol. 695 72

We have studied four children (ages 6 to 17 years) with chronic cholestasis who developed a slowly progressive neuromuscular disease characterized by ataxia, dysmetria, areflexia, loss of vibratory sensation, and a variable ophthalmoplegia. Serum vitamin E concentration were low in all patients prior to treatment. Muscle histochemical studies in all four patients showed autofluorescent basophilic esterase and acid phosphatase-positive cytoplasmic inclusions and occasional necrotic fibers. These distinctive muscle changes are similar to those described in vitamin E-deficient animals. Intramuscular injections of alpha tocopherol were required in three patients to achieve normal serum vitamin E values. High-dose oral supplementation was effective in one patient. After normalization of serum vitamin E concentrations for six to 14 months, the neurologic disease has improved in all four patients.
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PMID:Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: diagnosis and treatment with alpha tocopherol. 705 16

The aim of the study was the estimation of metabolic changes in rat brain histaminergic neurons in dynamics of subhepatic cholestasis. The investigation was carried out in male Wistar rats using the quantitative histochemical methods. It was found that cholestasis induced significant changes in the activity of dehydrogenases of succinate, lactate, glucose-6-phosphate, NADH and NADPH, as well as of acid phosphatase and type B monoamine oxidase in hypothalamic histaminergic neurons. These changes depended on the duration of cholestasis and had the dynamic, undulating pattern. They were demonstrated already after 5 days of cholestasis, reached their maximum by 10-20 days, were decreased at 45 days and disappeared after 90 days.
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PMID:[Metabolic changes in rat brain histaminergic neurons in dynamics of subhepatic cholestasis]. 1796 24


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