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 previous studies we have shown that male rats carrying genes controlling growth and reproduction (grc) linked to the major histocompatibility complex (MHC) to be more susceptible to N-2-acetylaminofluorene than rats without grc genes. In the present studies we show that by manipulation of the diet of grc rats, hepatocarcinogenesis induced by another carcinogen can be altered. Male rats with the grc gene (R16) and wild type (ACP) were initiated with diethylnitrosamine (DEN) (200 mg/kg body weight). Some were fed laboratory chow (LC) for 9 months; others were fed a choline-supplemented (CS) or a choline-deficient (CD) diet. The rats were killed at various time periods and the liver sections were stained with H&E and for gamma-glutamyltranspeptidase (GGT). After 9 months on LC, the livers of R16 showed greater size and number of GGT-positive foci, bile duct proliferation, cellular atypia, cirrhosis, and nodular hyperplasia than the ACP. While the first hepatocellular carcinoma in R16 fed either a CS or LC was seen at 9-10 months, one R16 rat fed a CD diet had liver cancer at 4 months. On a CS diet the R16 showed greater GGT-positive foci at 2 months than the ACP. On a CD diet the R16 showed even greater size and number of GGT-positive foci. At 12 months, 15 of 22 (68%) of the R16 rats on a CD diet had liver cancer and seven of 24 (29%) of the R16 on a CS diet. Of the ACP, none of 15 (0%) on CS and one of 18 (6%) on CD diet had liver tumors. The results show that the grc genes confer high susceptibility to liver cancer, which is enhanced by a CD diet, suggesting synergism between genetics and diet.
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PMID:Genetics and diet: synergism in hepatocarcinogenesis in rats. 215 63

The morphologic evolution of hepatitis B virus (HBV) liver disease in 45 hepatic allograft recipients who were HBV surface-antigen positive (HBs-Ag+) at the time of liver replacement and who survived for more than 60 days was studied by routine histologic and immunocytochemical analysis of serial pathology specimens. The findings in these patients were compared to a control group of 30 individuals who were immune to the HBV (anti-HBs antibody positive), but required hepatic replacement for other reasons. Eight of the forty-five (18%) HBsAg-positive patients have no serologic evidence of HBV reinfection after transplantation. All 37 remaining patients are reinfected; 21 (47%) developed chronic active hepatitis and/or cirrhosis, 3 (7%) developed submassive necrosis, and 6 (14%) developed chronic lobular hepatitis. One patient lost her graft to chronic rejection, despite reinfection with the B virus. Four other patients (9%) developed a chronic carrier state. No long-term follow-up biopsies were available in the remaining two patients. The histologic features associated with dysfunction related to recurrent HBV infection evolved from an acute to chronic phase and were similar to hepatitis B seen in nonallografted livers. Furthermore HBV-related lesions could be separated from rejection using routine histology alone. The only exception to this conclusion was the occurrence of a peculiar HBV-related lesion in two recipients, described herein. Immunohistochemical analysis demonstrated the presence of viral antigens in almost all cases. Hepatic inflammation also was commonly present during HBV disease and consisted mostly of accessory cells and T lymphocytes. Analysis of the effect of major histocompatibility complex matching revealed no clear association between the number of class I or II matches or mismatches and the development, or pattern, of active hepatitis in the allograft. Peculiar pathologic alterations in several of the biopsies and failed allografts after HBV reinfection suggests that, under special circumstances, the B virus may be cytopathic.
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PMID:Evolution of hepatitis B virus liver disease after hepatic replacement. Practical and theoretical considerations. 239 36

Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.
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PMID:Successful liver allografts in mice by combination with allogeneic bone marrow transplantation. 352 May 75

Using antibodies directed to beta 2-microglobulin (b2-m) and HLADR antigens, the expression of MHC products by normal and abnormal bile ducts in 90 paraffin-embedded biopsies showing various liver diseases, was studied. Normal and abnormal bile ducts constantly expressed b2-m. Increased b2-m expression was found in 17/19 PBC, and 4/7 chronic aggressive hepatitis or cirrhosis of viral etiology with hepatitic bile duct lesions. Normal bile ducts failed to express HLADR antigens. Aberrant HLADR display was found in 24/26 PBC and 10/16 chronic aggressive hepatitis or cirrhosis of viral etiology with hepatitic bile duct lesions. It is concluded that the pattern of the major histocompatibility complex (MHC) display does not discriminate between PBC and hepatitic bile duct lesions. Enhanced expression of class I MHC products at the surface of medium-sized bile ducts in PBC may render these structures more susceptible to lysis by cytotoxic T-cells, whereas its significance in chronic aggressive hepatitis or cirrhosis remains unknown. Aberrant expression of HLADR antigens by abnormal bile ducts in PBC and chronic aggressive hepatitis or cirrhosis of viral etiology is probably induced by gamma-interferon, liberated by intra-epithelial lymphocytes, and may serve to enhance the immune response, either by attracting HLADR-restricted cytotoxic T-cells or by the presentation of non-self antigens at the surface of bile duct epithelium.
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PMID:Expression of MHC products by normal and abnormal bile duct epithelium. 354 67

In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR) as well as A and B locus antigens were typed serologically. For 14 patients carrying HLA-B8 and DRw3 family members were typed to establish haplotypes. Control groups consisted of healthy persons and patients with chronic liver disease unrelated to autoimmune CAH (alcoholic cirrhosis and cryptogenic cirrhosis). In autoimmune CAH, DRw3 was significantly increased, 74%, compared with healthy controls, 32%, and liver controls, 31%, this increase being similar to the increase of HLA-B8. There was marked co-occurrence of HLA-B8 and DRw3 in 31 of 33 individuals positive for either antigen. DRw3 was present in 23 of the 24 cases with disease-onset before age 30 hr. HLA typing on the 14 families showed that a haplotype including B8 and DRw3 was present in all index patients; this haplotype also included A1 in 10 cases, A9 in 2 cases, and A2 and A28 in 1 case. The results indicate that in the autoimmune type of chronic active hepatitis occurring characteristically in young females, there exists a disease susceptibility gene strongly associated with the B and D locus of the major histocompatibility complex (MHC), and acting in concert with other non-MHC gene loci and/or environmental factors.
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PMID:HLA associations with autoimmune-type chronic active hepatitis: identification of B8-DRw3 haplotype by family studies. 738 Feb 29

MUC1 apomucin is a specific target tumor antigen recognized by cytotoxic T cells in a major histocompatibility complex (MHC) unrestricted fashion in patients with pancreatic and breast cancer. This T-cell-mediated immune mechanism against MUC1 apomucin expressing cells has not been evaluated in nonneoplastic immune-mediated diseases. Therefore, we immunohistochemically surveyed the expression of MUC1 apomucin on biliary epithelial cells of small bile ducts in various hepatobiliary diseases, including primary biliary cirrhosis (PBC). MUC1 apomucin was detected using the monoclonal antibody DF3 and the streptavidin-biotin complex, in livers from 31 patients with PBC, 67 with chronic viral hepatitis (CH) with or without cirrhosis, 31 with extrahepatic biliary obstruction (EBO), 30 with hepatolithiasis, and from 23 normal individuals. MUC1 apomucin was infrequently and focally expressed in the biliary epithelial cells of the small bile ducts in 3 of 23 normal livers. In contrast, MUC1 apomucin was frequently and strongly expressed on the luminal surface of biliary epithelia] cells of small bile duct, in 22 of 31 patients with PBC, and in 50 of 67 patients with CH. In particular, high levels of MUC1 apomucin were expressed in bile ducts showing chronic nonsuppurative destructive cholangitis (CNSDC) in PBC and hepatitic duct injuries in CH. In EBO and hepatolithiasis, MUC1 apomucin was focally and weakly expressed in 29% and 30% of livers examined, respectively. More MUC1 apomucin was expressed in PBC and CH than in EBO, hepatolithiasis, and normal liver (P < .01, respectively). Frequent and high luminal expression of MUC1 apomucin on biliary epithelial cells in damaged small bile ducts in PBC and CH may be related to T-cell-mediated immunologic mechanisms in these diseases, probably by an MHC-unrestricted recognition process.
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PMID:Frequent expression of MUC1 apomucin on biliary epithelial cells of damaged small bile ducts in primary biliary cirrhosis and chronic viral hepatitis: an immunohistochemical study. 867 44

Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood. It is most likely that both viral and host factors contribute to HCV persistence. This review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions between the virus and the host during HCV infection. Expansion of B lymphocytes and antibody production to virtually any HCV protein can be detected in most infected patients. However, observations in HCV-infected humans as well as experimental infections in chimpanzees suggest that natural HCV infection does not induce protective immunity, and reinfection can readily be demonstrated after inoculation with homologous or independent strains in HCV-seroconverted animals. Nevertheless, the immune system may gain partial control over HCV even in patients with chronic infection, as HCV infection in severely immunocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure. Cytotoxic CD8+ T lymphocyte responses to HCV proteins have been characterized in peripheral blood and liver tissue and were found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few major histocompatibility complex molecules were considered restriction elements. Immunoregulation may be particularly important in HCV infection. The HCV core and NS4 proteins appear to be most immunogenic for peripheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are preferentially compartmentalized to the liver. However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients. Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection. This unusual T-B cell relationship may be the consequence of an altered cytokine release during HCV infection. Alternatively, this virus may have found devices that can disturb immunoregulation in infected patients. A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease.
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PMID:Immune responses in hepatitis C virus infection. 883 85

The pathogenesis of biliary atresia (BA) is still unknown. Progression to cirrhosis despite restoration of bile flow by successful portoenterostomy suggests that it is a progressive disease of the liver and biliary tree. Whether immunologic factors play any role in the development of this disease remains uncertain. Aberrant expression of major histocompatibility complex (MHC) Class II antigens of HLA-DR on hepatocytes and biliary epithelium is regarded as important in the progression of hepatocellular and biliary damage mediated by cytotoxic T cells. This study was undertaken to evaluate expression of MHC Class II antigen and macrophage-associated antigens (CD68) in liver of patients with biliary atresia to determine their prognostic usefulness and possible role in the pathogenesis of the disease. Liver biopsy specimens from infants with BA (n = 15), neonatal hepatitis (n = 3), and normal livers (n = 6) were studied using an indirect immunoperoxidase staining using antibodies against MHC Class II antigen and macrophage-associated antigens (CD68) as well as routine H&E and Masson's trichome stain. In patients with biliary atresia, the liver biopsy specimen was obtained at the time of Kasai portoenterostomy. Expression of HLA-DR antigens and CD68 antigens was either absent or minimal in normal liver biopsy specimens. There were a few HLA-DR antigens and a few CD68-positive cells around portal tracts in all patients with neonatal hepatitis and five of the seven biliary atresia patients with successful Kasai portoenterostomy. In contrast, there was strong expression of HLA-DR antigen in bile ductules, inflammatory cells, and adjacent damaged hepatocytes and marked CD68-positive macrophage infiltrate in the portal tracts as well as hepatic lobules in two patients with good prognosis and in all eight patients with bad prognosis. Hepatic expression of MHC Class II antigen and CD68 antigens correlated well with the severity of clinical course in patients with BA and may act as a prognostic factor in these patients.
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PMID:Hepatic overexpression of MHC class II antigens and macrophage-associated antigens (CD68) in patients with biliary atresia of poor prognosis. 912 61

Infection by hepatitis C virus (HCV) is a growing public-health concern. After infection, 80% of infected subjects develop chronic viremia. Some developing chronic liver disease, liver cirrhosis, and hepatocellular carcinoma several years after the initial infection. The remaining 20% are able to control the infection, clearing the virus spontaneously. It is generally accepted that genes within the major histocompatibility complex play a central role in the development of the immune response against HCV. The search has focused on HLA gene products to identify disease susceptibility genes. No significant associations were shown between HLA class I and disease or response to interferon therapy. Several studies have shown an association of class II alleles with clinical outcome after HCV infection. However, which genes are associated with one outcome or another seems to depend on the ethnicity of the infected. Only spontaneous hepatitis virus clearance has been described as being strong associated with mainly, DQB1*0301 or DRB1*1101, DRB1*1104 alleles.
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PMID:[Association between HLA antigens and hepatitis C virus (HCV) infection]. 1559 39

More than 170 million people worldwide are chronically infected with hepatitis C virus (HCV), which is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Impaired T-cell reactivity to HCV, a hallmark of inefficient adaptive immunity, is believed to be responsible for the high propensity of HCV to cause chronic infection. Dendritic cells are the most potent antigen-presenting cells and many viruses affect various dendritic cell functions. Data suggest that such changes induced by HCV may have an important role in viral persistence. HCV has been shown to bind to dendritic cells, although viral replication within these cells occurs at a very low level. Dendritic cells from people with chronic HCV infection are impaired in their capacity to stimulate T cells. This impairment may be a consequence of changes in the expression of major histocompatibility complex and costimulatory molecules on its surface, as well as in the production of cytokines such as interleukin 12. In addition, hepatic dendritic cells may be affected by the tolerogenic microenvironment of the liver, possibly generating dendritic cells that promote regulatory T cells, which suppress the cellular immune response mounted against HCV.
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PMID:Is hepatitis C virus infection of dendritic cells a mechanism facilitating viral persistence? 1585 85


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