Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.
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PMID:Oral cancer. 212 24

Proliferation of the two types of bile ductules, typical and atypical, in the portal and periportal areas was examined in various liver diseases other than cirrhosis to determine any difference in their immunohistochemical properties and presumed histogenesis. While the typical ductules with a well-formed lumen were frequently seen in a large spectrum of diseases, atypical ductules with a poorly defined lumen were encountered much more frequently in prolonged biliary diseases, including primary biliary cirrhosis and primary sclerosing cholangitis, than in nonbiliary hepatic diseases. Immunocytochemically, cytoplasmic keratin was intensively positive in typical ductules, and the degree of its intensity and extent was variable in atypical ductules. Simultaneously, some of the periportal hepatocytes revealed weak staining for keratin. Luminal borders of typical ductules usually revealed an expression of both carcinoembryonic antigen and epithelial membrane antigen, while atypical ductules and periportal hepatocytes lacked epithelial membrane antigen. The atypical ductules, together with the adjoining hepatocytes, appeared on occasion to form anastomosing cords in prolonged biliary diseases. Thus, atypical ductules seem likely to originate from ductular transformation of the periportal hepatocytes and the typical ductules might result from the proliferation of preexisting interlobular bile ducts and ductules.
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PMID:Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseases. 243 Jan 63

In the last years, considerable advances have been made in the study of the proteins and polypeptides of the cytoskeleton, and its three main components: microfilaments (MF), intermediate filaments (IMF) and microtubules (MT). The principal properties of these elements and those of many associated proteins are recalled. The actin MF are mainly involved in cell contractility, the IMF in cell shape, while the MT and their associated proteins are involved in intracellular transport. Some pathological modifications of the cytoskeleton will be considered. In the liver, accumulations of keratin result in the formation of Mallory's hyalin, found in several types of cirrhosis and hepatomas. In muscle, accumulations of desmin are observed in various myopathies. An accumulation of alpha-actinin at the Z bands characterizes nemalin myopathy. In several forms of hemolytic anemias, alterations of the membranous cytoskeletal components of the red blood cells--spectrin, ankyrin, actin--may explain their abnormal shape and excessive fragility. In the nervous system, many pathological conditions are related to abnormal cytoskeletal components. In Parkinson's disease, Lewy bodies are an accumulation of neurofilaments (IMF). In Alzheimer's disease, and some related conditions, the intraneuronal tangles are associated with modifications of MT and neurofilaments. The role of MT and in particular of the MT-associated protein tau, as demonstrated recently, confirms the involvement of the MT. The observed disturbances of MT-related axonal flow may explain some of the known functional changes in these forms of dementia.
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PMID:[Pathology of the cytoskeleton]. 329 78

The possible involvement of bile duct epithelium (BDE) in chronic hepatitis B was examined by immunohistochemical investigation of HBcAg and HBsAg expression in biliary cells in 47 liver biopsies with both viral antigens detectable in hepatocytes. HBcAg- and HBsAg-positive cells were identified in nine and five cases, respectively, in atypical and occasionally in typical ductules in cases of acute exacerbation, chronic active hepatitis and active cirrhosis. Atypical ductules were usually located in areas of periportal fibrosis and in cirrhotic septa. Liver cell plates expressing viral markers and undergoing ductular transformation (positive reaction of hepatocytes to BDE-specific, wide-spectrum keratin) were also observed in acinar zone 1, at the periphery and within parenchymal nodules in a number of cases. The presence of both viral antigens in atypical ductules in cases of advanced chronic liver disease most probably expresses the persistence of the virus in cells deriving from biliary metaplasia of infected hepatocytes. However, the detection of the virus in a few typical ductules is indicative of a direct viral infection. According to these findings, ductular cells seem to serve as a suitable host for HBV, their genotype permitting viral replication and antigen production.
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PMID:HBcAg and HBsAg expression in ductular cells in chronic hepatitis B. 819 12

We present a rare case of hepatic recurrence of cholangiolocellular carcinoma in a 61-year-old woman. The patient's past history included a right hepatic lobectomy and a hepatic hilar resection with hepaticojejunostomy for cholangiolocelluar carcinoma in 1990. After the diagnosis of hepatic recurrence in 1993, a partial hepatic resection was performed. The gross specimen showed an irregularly shaped white nodular tumor 2.5 cm in size without liver cirrhosis. The histopathological findings revealed small cuboidal cells resembling cholangiole forming acinar structures with fibrotic stroma, these findings were the same as those in the previously resected tumor. An immunohistochemical examination showed a positive reaction to carcinoembryonic antigen and keratin. The ultrastructural features revealed small round nuclei, flat contact of the cell membranes without interdigitation resembling that of hepatocytes, relatively numerous intracytoplasmic filaments, few organelae and a basement membrane resembling those of the bile duct epithelium. No recurrence has been observed during a one-year follow up. On the basis of the characteristic clinical and histopathological features of this case, we therefore consider that cholangiolocellular carcinoma should be recognized as an intermediate type somewhere between hepatocellular and cholangiocellular carcinoma.
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PMID:Hepatic recurrence of cholangiolocellular carcinoma: report of a case. 888 37

Mutations in 11 of the more than 20 keratin intermediate filaments cause several epidermal and oral associated diseases. No disease-associated mutations have been described in keratin 8 or 18 (K8/18) which are the major keratin pair in simple-type epithelia, as found in the liver, pancreas, and intestine. However, transgenic mice that express mutant keratin 18 develop chronic hepatitis, and have an increased susceptibility to drug-induced hepatotoxicity. Also, ectopic expression of epidermal K14 in mouse liver results in chronic hepatitis, and disruption of mouse K8 leads to embryo lethality with extensive liver hemorrhage. We tested if patients with liver disease of unknown cause may harbor mutations in K18. We describe a his127-->leu (H127L) K18 mutation in a patient with cryptogenic cirrhosis that is germline transmitted. The K18 H127L isolated from the liver explant, or after expression in bacteria, showed an altered migration on two-dimensional gel analysis as compared with normal human liver or bacterially expressed K18. Electron microscopy of in vitro assembled K18 H127L and wild type K8 showed an assembly defect as compared with normal K8/18 assembly. Our results suggest that mutations in K18 may be predispose to, or result in cryptogenic cirrhosis in humans.
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PMID:Mutation of human keratin 18 in association with cryptogenic cirrhosis. 901 70

AIM:To investigate the expression of integrins in rats liver during 3'-Me -DAB induced hepatocarcinogenesis and to find out the relationship between integrins and liver cancer metastasis.METHODS:The expressions of integrins alpha(1), alpha(2), alpha(3) and alpha(5) and epidermal keratin (EK) were observed by immunohisto chemical PAP method.RESULTS:In the normal liver tissues, hepatocytes express integrins alpha(1) and alpha(5) and in the bile duct epithlium, EK. In liver cirrhosis, hepatocytes highly express integrins alpha(1), alpha(2), alpha(3) and alpha5and in hyperplastic bile duct epithelium, integrins alpha(1), alpha(5) and EK. Expression of integrins alpha(1), alpha(2), alpha(3) and alpha(5) were obviously decreased in the preneoplastic nodules and primary carcinoma but expressions of integrins alpha(1) and alpha(5) in metastasis in the lung and diaphragma were higher than those in primary carcinoma.CONCLUSION:Integrins alpha(1) and alpha(5) may play a major role in chemically induced hepatocarcinogenesis and metastasis in rats.
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PMID:Changes of integrin expression in rat hepatocarcinogenesis induced by 3'-Me-DAB. 1181 63

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.
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PMID:Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. 1217 85

Keratins are the type I and II intermediate filament proteins which form a cytoskeletal network within all epithelial cells. They are expressed in pairs in a tissue- and differentiation-specific fashion. Epidermolysis bullosa simplex (EBS) was the first human disorder to be associated with keratin mutations. The abnormal keratin filament aggregates observed in basal cell keratinocytes of some EBS patients are composed of keratins K5 and K14. Dominant mutations in the genes encoding these proteins were shown to disrupt the keratin filament cytoskeleton resulting in cells that are less resilient and blister with mild physical trauma. Identification of mutations in other keratin genes soon followed with attention focussed on disorders showing abnormal clumping of keratin filaments in specific cells. For example, in bullous congenital ichthyosiform erythroderma, clumping of filaments in the suprabasal cells led to the identification of mutations in the suprabasal keratins, K1 and K10. Mutations have now been identified in 18 keratins, all of which produce a fragile cell phenotype. These include ichthyosis bullosa of Siemens (K2e), epidermolytic palmoplantar keratoderma (K1, K9), pachyonychia congenita (K6a, K6b, K16, K17), white sponge nevus (K4, K13), Meesmann's corneal dystrophy (K3, K12), cryptogenic cirrhosis (K8, K18) and monilethrix (hHb6, hHb1).In general, these disorders are inherited as autosomal dominant traits and the mutations act in a dominant-negative manner. Therefore, treatment in the form of gene therapy is difficult, as the mutant gene needs to be inactivated. Ways of achieving this are actively being studied. Reliable mutation detection methods from genomic DNA are now available. This enables rapid screening of patients for keratin mutations. For some of the more severe phenotypes, prenatal diagnosis may be requested and this can now be performed from chorionic villus samples at an early stage of the pregnancy. This review article describes the discovery of, to date, mutations in 18 keratin genes associated with inherited human diseases.
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PMID:The molecular genetics of keratin disorders. 1268 39

Hepatocytes express keratins 8 and 18 (K8/18) as their only cytoskeletal intermediate filament (IF) proteins, and K8/18 mutations predispose their carriers to liver cirrhosis. Transgenic mice that overexpress mutant human K18 (Arg89-->Cys [R89C]) develop mild chronic hepatitis, hepatocyte fragility, keratin filament disruption, and increased susceptibility to drug-induced liver injury. K18 is a major caspase substrate during apoptosis, and K8- or K18-null mice are significantly predisposed to Fas- and possibly tumor necrosis factor (TNF)-mediated apoptosis in the liver. Here we tested the potential role of the K18 R89C mutation on Fas- or TNF-mediated apoptotic liver injury by injecting Fas antibody (Ab) or TNF-alpha plus actinomycin D into mice that overexpress wild-type (WT) human K18 (with intact filament network, termed TG2 mice) or into K18 R89C mice (with disrupted filament network). K18 R89C mice are significantly more susceptible to Fas-mediated liver injury compared with nontransgenic and TG2 mice. This included differences in lethality, histology, apoptosis, and serum transaminase levels. In contrast, K18 WT and R89C mice manifest similar sensitivity to TNF-induced injury. Both Fas- and TNF-induced apoptosis in liver tissues are associated with caspase-mediated K18 degradation and increased keratin phosphorylation on several but not all sites. In conclusion, transgenic mouse K18 mutation and its consequent keratin filament disruption predispose hepatocytes to Fas- but not TNF-mediated apoptotic injury. This supports the association of keratin mutations with cirrhosis in patients with liver disease and suggests that keratins modulate apoptosis induced by Fas but not TNF.
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PMID:Keratin mutation in transgenic mice predisposes to Fas but not TNF-induced apoptosis and massive liver injury. 1271 81


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