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)

The clinical, biochemical and histological characteristics of 13 cases of acute hepatitis A were evaluated. In 10 biopsies moderate to severe cholestasis was seen consisting of bile thrombi, cholestatic liver cell rosettes and ductular transformation of hepatocytes as shown on keratin- and S-100 immunostaining. The periportal spotty necrosis may play a role in the pathogenesis of cholestasis in hepatitis A by creating an interruption in continuity of bile flow. In 6 cases, abnormal ductular epithelium was seen resembling the ductular lesion in septicemia. Such ductular lesion may be related to the accumulation of leucotrienes as a result of cholestasis.
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PMID:Cholestatic features in hepatitis A. 302 88

This report describes two patients with hepatic epithelioid hemangioendothelioma: a 33-year-old woman and a 28-year-old man. The first case presented with a palpable abdominal mass and has survived without treatment for 6 years since diagnosis, with ascites but a good general condition. The other patient presented with abdominal pain and cholestasis. He had a rapid course and death occurred 6 months after the onset of symptoms. Histologically the tumors consisted of a proliferation of neoplastic cells with an angiogenic tendency embedded in a myxohyaline stroma. Positivity for the factor VIII-related antigen, for UEA-I and for vimentin and negativity for keratin of the neoplastic cells in the immunohistochemical investigation permitted identification of their endothelial origin. In both cases, the initial diagnosis was erroneous.
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PMID:Epithelioid hemangioendothelioma of the liver: report of two cases. 313 May 36

We report a rare case of a 10 year old girl diagnosed as having Alagille syndrome on the basis of a characteristic face, posterior embryotoxon, cholestasis, peripheral pulmonary artery stenosis and the absence of interlobular bile ducts in a liver biopsy at 1.5 years of age. Since 1.5 years old, she had been in good health without medication and the serum biochemical liver function tests indicated no progression of cholestasis. A second liver biopsy at 9.5 years of age showed normal interlobular bile ducts confirmed by anti-keratin staining at each of the five examined portal areas. Alagille syndrome is usually associated with the progressive disappearance of interlobular bile ducts. The findings of interlobular bile ducts in the second liver biopsy were therefore rare and unique to this case.
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PMID:Alagille syndrome with a spontaneous appearance of the interlobular bile ducts. 782 52

This review summarizes pathobiochemical aspects of diseases, in which cytoskeletal components play a crucial role in pathogenesis. An attempt to classify the disorders on the basis of phenotypic changes that occur in microfilaments, intermediate filaments and microtubuli was unsuccessful. Three groups of disorders are presented: 1. cytoplasmic inclusions in specific diseases (merely descriptive); 2. diseases with genetic defects in cytoskeletal proteins (a chain of causality from defect to phenotype, in some cases with large gaps); 3. diseases with suspected involvement of cytoskeleton (hypothetical causal chain). Microfilaments are involved in certain pathogenetic processes on account of defects in their associated proteins; in Duchenne muscular dystrophy, dystrophin is defective, while the defective protein in Rett syndrome is synapsin. Defects in spectrin and membrane anchor proteins lead to disorders of the red cell membrane skeleton (congenital haemolytic anaemias). Intermediate filaments accumulate in some types of cytoplasmic inclusions, together with ubiquitin (Mallory bodies, desmin accumulation in some myopathies and others). A pathogenetic interpretation of this phenomenon is lacking. A genetic defect in certain types of keratin is the cause of epidermolysis bullosa. Interesting preliminary results are reviewed that reveal the crucial role of cytoskeletal components in a further group of diseases (intrahepatic cholestasis, Alzheimer disease, pemphigus). These disorders are currently under investigation, or are of theoretical interest with respect to the cytoskeleton. Specific reactions of cytoskeletal components in serum, which might be used diagnostically, have not been found.
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PMID:Pathobiochemical aspects of cytoskeleton components. 821 79

Mallory bodies (MBs) are characteristic morphologic features of alcoholic hepatitis but are also associated with non-alcoholic liver diseases including long lasting cholestasis, metabolic and neoplastic disorders. MBs contain in addition to keratins non-keratin components, including microtubule-associated (tau protein) and other not yet characterized proteins in an aggregated form. Aggregation of these components in the cell is promoted by posttranslational modifications, such as partial proteolysis, phosphorylation and cross-linking, and may result in functional and structural disturbances of the cell depending on the physiologic function of the components involved. Several enzymes responsible for these modifications are Ca(++)-dependent. Thus, disturbance of Ca(++)-homeostasis may play an essential role in the pathogenesis of MBs. In some structural aspects MBs closely resemble inclusions associated with degenerative disorders of the central nervous system, including Alzheimer's and Parkinson's disease. Studies on the pathogenesis of MBs, therefore, not only shed light on a peculiar type of liver cell injury but may also assist in the understanding of other chronic degenerative diseases, particularly those of the central nervous system.
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PMID:Alcoholic liver disease: molecular-pathologic aspects. 860 Jun 92

The keratin intermediate filament (IF) cytoskeleton of hepatocytes has continuously gained medical relevance over the last two decades. Originally it was mainly recognized as a differentiation marker for diagnostic purposes in pathology. However, keratin IFs were soon identified as major cellular structures to be affected in a variety of chronic liver diseases, such as alcoholic and non-alcoholic steatohepatitis (ASH, NASH), copper toxicosis, and cholestasis. Based on observations in keratin gene knock-out mice, the insight into the functional role of keratins was extended from a mere structural role providing mechanical stability to hepatocytes, to an additional role as target and modulator of toxic stress and apoptosis. The functional relevance of keratins in human diseases has recently been underlined by the identification of mutations in keratin genes in patients with liver cirrhosis.
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PMID:The keratin cytoskeleton in liver diseases. 1549 50

Inclusion bodies are characteristic morphological features of various neuronal, muscular and other human disorders. They share common molecular constituents such as p62, chaperones and proteasome subunits. The proteins within aggregates are misfolded with increased beta-sheet structure, they are heavily phosphorylated, ubiquitinylated and partially degraded. Furthermore, involvement of proteasomal system represents a common feature of virtually all inclusions. Multiple aggregates contain intermediate filament proteins as their major constituents. Among them, Mallory-Denk bodies (MDBs) are the best studied. MDBs represent hepatic inclusions observed in diverse chronic liver diseases such as alcoholic and non-alcoholic steatohepatitis, chronic cholestasis, metabolic disorders and hepatocellular neoplasms. MDBs are induced in mice fed griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine and resolve after discontinuation of toxin administration. The availability of a drug-induced model makes MDBs a unique tool for studying inclusion formation. Our review summarizes the recent advances gained from this model and shows how they relate to observations in other aggregates. The MDB formation-underlying mechanisms include protein misfolding, chaperone alterations, disproportional protein expression with keratin 8>keratin 18 levels and subsequent keratin 8 crosslinking via transglutaminase. p62 presence is crucial for MDB formation. Proteasome inhibitors precipitate MDB formation, whereas stimulation of autophagy with rapamycin attenuates their formation.
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PMID:Mallory-Denk-bodies: lessons from keratin-containing hepatic inclusion bodies. 1880 82

Keratins (K) are cytoprotective proteins and keratin mutations predispose to the development of multiple human diseases. K19 represents the most widely used marker of biliary and hepatic progenitor cells as well as a marker of ductular reaction that constitutes the basic regenerative response to chronic liver injury. In the present study, we investigated the role of K19 in biliary and hepatic progenitor cells and its importance for ductular reaction. K19 wild-type (WT) and knockout (KO) mice were fed: (a) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC); (b) cholic acid (CA); (c) a choline-deficient, ethionine-supplemented (CDE) diet; or (d) were subjected to common bile duct ligation (CBDL). The bile composition, liver damage, bile duct proliferation, oval cell content and biliary fibrosis were analysed. In untreated animals, loss of K19 led to redistribution of the K network in biliary epithelial cells (BECs) but to no obvious biliary phenotype. After DDC feeding, K19 KO mice exhibited (compared to WTs): (a) increased cholestasis; (b) less pronounced ductular reaction with reduced ductular proliferation and fewer oval cells; (c) impaired Notch 2 signalling in BECs; (d) lower biliary fibrosis score and biliary bicarbonate concentration. An attenuated oval cell proliferation in K19 KOs was also found after feeding with the CDE diet. K19 KOs subjected to CBDL displayed lower BEC proliferation, oval cell content and less prominent Notch 2 signal. K19 deficiency did not change the extent of CA- or CBDL-induced liver injury and fibrosis. Our results demonstrate that K19 plays an important role in the ductular reaction and might be of importance in multiple chronic liver disorders that frequently display a ductular reaction.
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PMID:Loss of keratin 19 favours the development of cholestatic liver disease through decreased ductular reaction. 2610 53