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)

Bile duct adenomas are small nodules that are usually found incidentally on the liver surface at abdominal surgery or autopsy. We recently analyzed two such lesions that, in addition to the typical small caliber ducts, contained periductular nests and clusters of uniform round cells, suggestive of endocrine cell proliferation. Follow-up of these patients did not show endocrine tumors elsewhere. The lesions were studied by immunohistochemistry (avidin-biotin-peroxidase technique) and compared with conventional bile duct adenomas (seven cases). The results showed these cells to decorate with several endocrine markers, namely, neuron-specific enolase, chromogranin, synaptophysin, and Leu-7. Endocrine markers were not seen in the cells of conventional bile duct adenomas. Epithelial markers, that is, cytokeratin (CAM 5.2 antibody) and epithelial membrane antigen, were expressed by the cells composing both conventional bile duct adenomas and those with endocrine-like cells, although with less intensity in the endocrine cell clusters. We suggest that some bile duct adenomas contain endocrine cell proliferations that morphologically may resemble a small carcinoid tumor or the so-called pulmonary tumorlet. Neurosecretory granules have previously been identified in some cholangiocarcinomas and in bile duct proliferation associated with cholestasis. The endocrine clusters in biliary adenomas may constitute a diagnostic pitfall and must be separated from metastases of carcinoids or islet cell tumors.
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PMID:Bile duct adenomas with endocrine component. Immunohistochemical study and comparison with conventional bile duct adenomas. 137 Jan 91

Proliferation of bile duct-like structures is a hepatic cellular reaction observed in most forms of human liver disease and in a variety of experimental conditions associated with liver injury. Yet the origin, means of initiation, and significance of this hyperplasia are unknown. To clarify these issues we induced bile duct proliferation in rats by ligating the common bile duct and studied (a) hepatic incorporation of [3H]thymidine by histoautoradiography, (b) hepatic morphometry, (c) biliary tree volume using [3H]taurocholate as a marker of biliary transit time, (d) immunohistochemical expression of cytokeratin no. 19, (e) the effect of indomethacin, and (f) the role of increased biliary pressure, in the absence of physiological and biochemical evidence of cholestasis, on [3H]thymidine incorporation by the bile-duct cells. The results have demonstrated that (a) the proliferating bile duct-like cells are products of the extant biliary epithelium and retain its characteristics; (b) bile duct cells divide irrespective of the size of the duct in which they are located and form a system with a lumen continuous with the preexisting one; (c) bile duct proliferation results mainly in elongation, not in circumferential enlargement or sprouting of side branches; (d) portal macrophage infiltration does not play a role in the hyperplastic reaction, and (e) increased biliary pressure is the initiating factor in bile duct cell division. Our results provide evidence that under the present conditions, ductular metaplasia of hepatocytes does not occur and there is no functioning stem cell for biliary epithelial growth segregated in any particular duct size or within the portal connective tissue.
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PMID:Origin, pattern, and mechanism of bile duct proliferation following biliary obstruction in the rat. 201 90

The effects of common bile duct ligation on hepatocytes in rats were investigated by light and electron microscopical techniques. Cytoskeletal elements such as actin and cytokeratin were immunohistochemically increased in liver cells after bile duct ligation. Electron microscopical observation revealed that bile canaliculi were rich in microvilli in the control liver, while in the experimental rats, the bile canaliculi were dilated. A decreased number of microvilli and bleb formations were also noted. In the cytoplasm, pericanalicular microfilaments and intermediate filaments were abundant. These findings suggest that increased biliary pressure may affect not only the hepatocellular plasma membrane constituents, but also the filamentous structure in the hepatocyte. Furthermore the congested bile acid affect may be worse after a common bile duct obstruction.
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PMID:[Experimental study on the cytoskeletal alteration of hepatocytes in obstructive jaundice with special reference to the significance of the localization of the intracellular filaments]. 228 43

Aggregation and derangement of cytokeratin intermediate filaments are thought to be the key mechanism in the formation of Mallory bodies in alcoholic liver disease (ALD). To study the incidence and patterns of intracellular distribution of aggregated cytokeratin and to determine its utility as a diagnostic marker of ALD, 108 liver biopsy specimens from patients with various liver abnormalities were examined by an avidin--biotin peroxidase complex technique on paraffin section using a monoclonal antibody to cytokeratins (Hybritech). In normal liver (n = 11), only bile duct epithelium was positive. Both bile ducts and hepatocytes were positive in pathologic livers (n = 97). In ALD, 82 per cent of cases (42 of 51) showed cytokeratin positivity versus 15 per cent (seven of 46) in nonalcoholic liver disease (e.g., chronic hepatitis, nonalcoholic cirrhosis, cholestasis, and primary biliary cirrhosis). The highest incidence (100 per cent, 37 of 37) of positivity was obtained in cases with alcoholic hepatitis and cirrhosis compared with only 36 per cent (five of 14) in alcoholic fatty liver. Mallory bodies were found by the immunoperoxidase method in 71 per cent of cases (30 of 42) versus in 40 per cent (17 cases) by hematoxylin--eosin stain. In alcoholic fatty liver and alcoholic hepatitis, centrilobular hepatocytes showed cytokeratin positivity, whereas such reactivity was seen predominantly at the periphery of the regenerative nodules in alcoholic cirrhosis. A rare periportal hepatocyte was positive in the nonalcoholic group. These findings suggest that the differential distribution patterns of aggregated cytokeratin may be helpful in differentiating alcoholic from nonalcoholic liver diseases.
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PMID:Distribution patterns of cytokeratin antigen determinants in alcoholic and nonalcoholic liver diseases. 243 6

The architectural framework of the pericanalicular sheath composed of cytokeratin intermediate filaments (IFs) was examined after phalloidin treatment, bile duct ligation, and alcoholic fatty liver in rats to assess the role of IFs in experimental cholestasis. Electron microscopy examination of whole mount unembedded extracted liver slices was employed to visualize the cytoskeleton. Immunofluorescence staining and immunoelectron microscopy of the sheath were also performed using monoclonal antibodies to rat hepatocyte cytokeratins CK49 and CK55. The thickness of the wall and the diameter of the lumens were measured. In the phalloidin-treated rats, the pericanalicular sheath was markedly dilated and thickened. Immunofluorescence staining showed that the CK49 and CK55 IFs were localized in the pericanalicular region, particularly in the pericentral area. Immunoelectron microscopy documented that the IFs at the thickened pericanalicular sheath consisted of both CK49 and CK55, which means that the thickening of the bile canaliculus was in part due to an increase of IFs and not just due to an increase in actin filaments. In the livers where the bile duct was ligated, the pericanalicular sheath was irregularly dilated and some parts of the sheath appeared thinned out or missing. The belt desmosome also appeared absent focally in the pericanalicular sheath. Immunofluorescence studies showed that the staining for CK49 and CK55 was reduced focally in the pericanalicular region. The CK55 antibody stained the cytoplasm of hepatocytes in the periportal area more intensely when compared with the controls. These results indicated that the pericanalicular sheath and the belt desmosome were focally disrupted in response to extrahepatic bile duct obstruction. In the ethanol-fed rats, the pericanalicular sheath was dilated, thickened and tortuous, and appeared focally flattened by large fat droplets. IFs in the cytoplasm were pushed to the cell periphery and were compressed against each other by the fat droplets. CK55 and CK49 appeared increased as indicated by the observed immunofluorescence at the pericanalicular region. Immunoelectron microscopy showed that IFs of the thickened pericanalicular sheath were composed of CK55 and CK49. It is suggested that the pericanalicular sheath functions to mechanically provide a scaffolding for the bile canaliculus which is vulnerable to the different forces involved in cholestasis of different pathogenesis such as focal compression and distortion by fat, hypertrophy in response to increased F actin and focal destruction by increased intracanalicular pressure.
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PMID:Pathologic changes in the cytokeratin pericanalicular sheath in experimental cholestasis and alcoholic fatty liver. 245 32

Cholestatic and hepatitic liver cell rosettes, gland-like formations found respectively in chronic cholestasis and in chronic active hepatitis, represent structural modifications of liver cell plates in response to injury. Differences in cytokeratin expression, ultrastructure and three-dimensional (3-D) configuration have been investigated. Cholestatic rosettes are considered to be a form of biliary metaplasia of hepatocytes, linking with newly-formed bile ductules in adjacent septa and probably providing some protection from injury caused by abnormal bile constituents. Hepatitis rosettes, by contrast, are a form of liver cell regeneration developing in isolated surviving hepatocytes or small groups of hepatocytes within areas of collapse.
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PMID:Liver cell rosettes: structural differences in cholestasis and hepatitis. 246 88

A cytokeratin immunohistochemical study was performed on 38 liver biopsies from cases of primary biliary cirrhosis, primary sclerosing cholangitis, extrahepatic biliary obstruction or drug-induced liver disease in order to analyse the cytoskeletal changes in detail. On paraffin sections of 27 cases, a variable number of hepatocytes were reactive with a polyclonal anti-cytokeratin antiserum that, in the normal liver, stains bile duct cells only. On cryostat sections of 23 cases, a variable number of hepatocytes were immunoreactive with a monoclonal antibody specifically directed against cytokeratin no. 7 and were most numerous in cases of long-standing cholestasis irrespective of the aetiology. In three cases of primary sclerosing cholangitis and two cases of primary biliary cirrhosis a few hepatocytes were also weakly positive with a monoclonal antibody specific for cytokeratin no. 19. Since cytokeratins no. 7 and no. 19 are, in the normal liver, restricted to bile duct cells, these results further support the concept of 'ductular metaplasia' of hepatocytes, the mechanism of which remains unclear.
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PMID:A cytokeratin immunohistochemical study of cholestatic liver disease: evidence that hepatocytes can express 'bile duct-type' cytokeratins. 247 70

The patterns of cytokeratin as determined by murine monoclonal antikeratin antibody lu-5 (mAb lu-5) were quantitated in paraffin-embedded liver tissue from normal and diseased subjects. In tissue from healthy medical students, mAb lu-5 was found to decorate 2-4 periportal and 2-3 perivenular cell layers. Alcoholic liver disease was accompanied by a marked increase in intensity of mAb lu-5 antigen expression in zone I and III hepatocytes. Moreover, additional liver cells of both zones were progressively recruited, so that in advanced lesions all three lobular zones became positive. In mechanical as well as in drug-induced cholestasis, a similar increase of mAb lu-5 antigen expression was already observed in earlier stages of disease, including an earlier recruitment of zone II hepatocytes. In both alcoholic and cholestatic biopsies the intensity and extent of mAb lu-5 epitope expression increased with the duration and severity of disease. In primary biliary cirrhosis (PBC) and seemingly also in primary sclerosing cholangitis the increase and extent was more marked in zone I, the zone of assumed cholate accumulation. Changes in zone III, the territory of histologic cholestasis (bilirubinostasis), became evident only in late stages of PBC. Mallory bodies of alcoholic and cholestatic liver disease showed an identical mAB lu-5 antigen expression, thus giving rise to four different staining patterns. Changes of cytokeratin expression are similar in alcoholic and cholestatic liver diseases. In chronic viral hepatitis, however, cytokeratin alterations are discrete and restricted to precirrhotic/cirrhotic stages.
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PMID:The common pattern of cytokeratin alteration in alcoholic and cholestatic liver disease is different from that of hepatitic liver damage. A study with the panepithelial monoclonal antibody lu-5. 750 54

The relationship between bile secretion (bile flow, bile acids, phospholipids, and cholesterol) and distribution of actin microfilaments (MFs) and cytokeratin (CK) intermediate filaments (IFs) was examined in hepatocytes of rats injected with a single low dose of phalloidin. This treatment induced a transient cholestasis characterized by a rapid development period (0-90 min postinjection) and a slow recovery period (24 h and 5 days postinjection). No significant changes were observed in bile acid secretion during the 5-day period. The phospholipid output dropped to less than 25% at 90 min and was back to the normal value at 24 h postinjection. In a parallel way, the cholesterol secretion dropped to 30% but came back to only 60% of the control level. Nile Red staining demonstrated a concomitant accumulation of lipids both in the cytoplasm and at the surface membrane. Immunostaining of the actin MFs and CK IFs showed that, in contrast with controls where both cytoskeletal networks were preferentially and uniformly localized at the surface membrane (i.e., sinusoidal, basolateral, and canalicular regions), the toxin treatment led to a major targeting of actin to the pericanalicular region at 24 h and a massive accumulation of well-preserved CK IFs in the cytoplasm at 5 days. Interestingly, this accumulation of CK IFs was not linked to any significant variations in CK isoforms. Together, these data indicate that a selective binding of the toxin to sinusoidal membrane actin at the time of injection triggers a sequence of events that culminate in delayed accumulation of actin MFs at the canalicular pole and of CK IFs in the cytoplasm. Moreover, the reversible perturbation of the bile secretory activity implies a functional adaptation of the hepatocytes that parallels the phalloidin-induced reorganization of both cytoskeleton networks.
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PMID:Biliary secretion and actin-cytokeratin filament distribution in rat hepatocytes during phalloidin-induced cholestasis. 871 84

We investigated the changes in hepatic cytokeratins in obstructive jaundice by immunohistochemistry. The results can be summarized as follows: 1) In accordance with the progression of the jaundice, the lobular and cellular distribution of cytokeratin reactivity in hepatocytes expanded. 2) Cytokeratin reactivity in obstructive jaundice was improved by removal of the bile duct obstruction (decompression), but this decompressive effect deteriorated in the case of prolonged jaundice. 3) It is suggested that the specific lobular and cellular distribution and/or the changes in cytokeratin aggregation might be of value in determining the stage and in predicting the prognosis of obstructive jaundice.
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PMID:Hepatic cytokeratin changes in obstructive jaundice: before and after biliary drainage. 886 53


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