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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two large kindreds manifesting the "cancer family syndrome" have been studied. Genetic and biologic studies reveal markers which have important implications for cancer detection, control and prevention. Valuable markers may be found in the major histocompatibility system, HL-A. The presence of carcinoembryonic antigen and SV-40 viral transformation of skin fibroblasts are other possibly important markers. Relationships of the ABO blood groups to cancer are under intensive study, as is the hepatitis-associated antigen.
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PMID:Clues to cancer risk: biologic markers. 4 90

Many reports have demonstrated an elevation of circulating carcinoembryonic antigen (CEA) in the majority of patients with alcoholic liver disease and, less frequently, in patients with nonalcoholic liver disease. Several explanations for this finding have been proposed, eg, increased production or release of CEA by the damaged liver, decreased hepatic metabolism, or diminished excretion of CEA of extrahepatic origin. In an attempt to clarify the mechanism of CEA elevation in liver disease, we have compared the CEA plasma level as measured by radioimmunoassay with CEA demonstrable in liver tissue by the indirect fluorescent antibody technique in 7 patients without significant changes in the liver biopsy specimen, 23 patients with alcoholic liver disease, and 16 patients with miscellaneous liver diseases such as acute or chronic nonalcoholic hepatitis or extrahepatic biliary obstruction. The mean CEA plasma level in patients with alcoholic liver disease was significantly higher than in patients with nonalcoholic liver disease (8.8 +/- 9.5 vs 2.7 +/- 2.5 ng/ml; P less than 0.02). In normal liver tissue, CEA was observed in the apical cytoplasm and along the luminal surface of bile duct epithelial cells, suggesting that under normal conditions CEA accumulates in and is excreted by bile ducts. In patients with alcoholic hepatitis and/or cirrhosis there was marked bile ductular proliferation and prominent cytoplasmic CEA-specific staining and both were associated with elevated CEA plasma levels in more than 80% of cases. In the group of miscellaneous liver diseases, bile ductule counts and CEA-specific staining did not correlate with CEA plasma levels. These observations suggest that proliferating bile ductules contribute to elevated plasma CEA in alcoholic patients.
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PMID:Carcinoembryonic antigen in normal and diseased liver tissue. 35 25

Human hepatic bile contains a glycoprotein (biliary glycoprotein I, BGP I) which cross-reacts with the carcinoembryonic antigen (CEA). A radioimmunoassay for BGP I was developed. The interference of CEA or 'non-specific cross-reacting antigen' (NCA) in the assay was small. The serum levels of BGP I were determined in healthy subjects, in patients with hepato-biliary diseases and in patients with various infectious or inflammatory disorders. Healthy individuals, including pregnant women, had a serum BGP I concentration of about 0.5-1 mg/l. Diseases of the liver or biliary tract (e.g. hepatitis A or B, cytomegalovirus hepatitis, obstructive jaundice or primary biliary cirrhosis) were associated with elevated serum levels of BGP I, as opposed to infectious diseases not affecting the liver mostly showing values within the normal range. Raised levels of serum BGP I activity may reflect biliary obstruction as a result of interference with normal BGP I secretion to the bile.
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PMID:Elevated serum levels of a biliary glycoprotein (BGP I) in patients with liver or biliary tract disease. 47 33

The SJL mouse strain is resistant to infection by some strains of the murine coronavirus mouse hepatitis virus (MHV), such as JHM and A59. The block to virus infection has been variously attributed to defects in virus receptors or virus spread. Since the cellular receptors for MHV, mmCGM1 and mmCGM2, have recently been identified as members of the carcinoembryonic antigen family, we reexamined the possible defectiveness of the MHV receptors in SJL mouse strain. Cloning and sequencing of the cDNAs of both mmCGMs RNAs from SJL mice revealed that they were identical in size to those of the susceptible C57BL/6 (B6) mouse. There was some sequence divergence in the N terminus of the mmCGM molecules between the two mouse strains, resulting in a different number of potential glycosylation sites. This was confirmed by in vitro translation of the mmCGM RNAs, which showed that the glycosylated mmCGM2 of SJL was smaller than that of B6 mice. However, transfection of either mmCGM1 or mmCGM2 from SJL mice into MHV-resistant Cos 7 cells rendered the cells susceptible to MHV infection. The ability of the SJL mmCGM molecules to serve as MHV receptors was comparable to that of those from B6. These molecules are expressed in SJL mouse brain and liver in a similar ratio and in amounts equivalent to those in the B6 mouse. Furthermore, we demonstrated that an SJL-derived cell line was susceptible to A59 but resistant to JHM infection. We concluded that the MHV receptor molecules in the SJL mouse are functional and that the resistance of SJL mice to infection by some MHV strains most likely results from some other factor(s) required for virus entry or some other step(s) in virus replication.
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PMID:The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection. 127 94

Like most coronaviruses, the coronavirus mouse hepatitis virus (MHV) exhibits strong species specificity, causing natural infection only in mice. MHV-A59 virions use as a receptor a 110- to 120-kDa glycoprotein (MHVR) in the carcinoembryonic antigen (CEA) family of glycoproteins (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; and R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). The role of virus-receptor interactions in determining the species specificity of MHV-A59 was examined by comparing the binding of virus and antireceptor antibodies to cell lines and intestinal brush border membranes (BBM) from many species. Polyclonal antireceptor antiserum (anti-MHVR) raised by immunization of SJL/J mice with BALB/c BBM recognized MHVR specifically in immunoblots of BALB/c BBM but not in BBM from adult SJL/J mice that are resistant to infection with MHV-A59, indicating a major difference in epitopes between MHVR and its SJL/J homolog which does not bind MHV (7). Anti-MHVR bound to plasma membranes of MHV-susceptible murine cell lines but not to membranes of human, cat, dog, monkey, or hamster cell lines. Cell lines from these species were resistant to MHV-A59 infection, and only the murine cell lines tested were susceptible. Pretreatment of murine fibroblasts with anti-MHVR prevented binding of radiolabeled virions to murine cells and prevented virus infection. Solid-phase virus-binding assays and virus overlay protein blot assays showed that MHV-A59 virions bound to MHVR on intestinal BBM from MHV-susceptible mouse strains but not to proteins on intestinal BBM from humans, cats, dogs, pigs, cows, rabbits, rats, cotton rats, or chickens. In immunoblots of BBM from these species, both polyclonal and monoclonal antireceptor antibodies that block MHV-A59 infection of murine cells recognized only the murine CEA-related glycoprotein and not homologous CEA-related glycoproteins of other species. These results suggest that MHV-A59 binds to a mouse-specific epitope of MHVR, and they support the hypothesis that the species specificity of MHV-A59 infection may be due to the specificity of the virus-receptor interaction.
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PMID:Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein. 127 3

Recently, we showed that a murine member of the carcinoembryonic antigen family of glycoproteins serves as a cellular receptor (MHVR) for the coronavirus mouse hepatitis virus A59 (MHV-A59) (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G.-S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; R. K. Williams, G.-S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). To examine the role of posttranscriptional modification of MHVR on virus-receptor interactions, a vaccinia virus-based expression system was employed. Expression from the vaccinia virus recombinant (Vac-MHVR) in BHK-21 cells resulted in high levels of MHVR glycoprotein on the cell surface and made these cells susceptible to MHV-A59 infection. Nonglycosylated core MHVR proteins were made in Vac-MHVR-infected BHK-21 cells in the presence of tunicamycin by in vitro translation of MHVR mRNA in a rabbit reticulocyte cell-free system in the absence of microsomal membranes and by expression of an N-terminal deletion clone of MHVR lacking its signal peptide. These three nonglycosylated MHVR proteins were recognized by polyclonal antibody against affinity-purified receptor but did not bind antireceptor monoclonal antibody (MAb) CC1 or MHV-A59 virions. Partial glycosylation of MHVR, either expressed in Vac-MHVR-infected cells treated with monensin or synthesized by in vitro translation with microsomal membranes, restored both the MAb CC1- and the virus-binding activities of the MHVR glycoprotein. Deletion of 26 amino acids at the carboxyl terminus of MHVR resulted in a secreted protein which was able to bind MAb CC1 and MHV-A59. These results suggest that either a carbohydrate moiety is an element of the MHVR-binding site(s) for virus and MAb CC1 or a posttranslational membrane-associated process is required for functional conformation of the receptor glycoprotein.
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PMID:Binding of the coronavirus mouse hepatitis virus A59 to its receptor expressed from a recombinant vaccinia virus depends on posttranslational processing of the receptor glycoprotein. 131 94

The cellular receptor for the murine coronavirus mouse hepatitis virus (MHV) has been identified as a member of the murine carcinoembryonic antigen (CEA) family (R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). However, the receptor protein was not detected in some of the susceptible mouse tissues. We therefore examined whether other types of MHV receptor might exist. By polymerase chain reaction with the conserved sequences of murine CEA gene family members (mmCGM) as primers, we detected two CEA-encoding RNAs in the mouse liver. One of them (1.3 kb) encodes mmCGM1, which has previously been identified as the receptor for MHV, and the other one (0.8 kb) was shown to encode another member of mouse CGM, mmCGM2. The sequence analysis showed that mmCGM2 lacks 564 nucleotides in the middle of the gene compared with mmCGM1. These two CEA transcripts are probably derived from the same gene by an alternative splicing mechanism. Expression of either of these cDNA clones in COS-7 cells rendered these cells susceptible to MHV infection, suggesting that not only mmCGM1 but also mmCGM2 serves as a receptor for MHV. The mmCGM2 was the major CEA species in the mouse brain, which is a main target organ for the neurotropic strains of MHV. Very little mmCGM1 was detected in the mouse brain or in cells of the susceptible mouse astrocytoma cell line DBT. This result indicates that MHV may utilize different CEA molecules as the major receptor in the mouse brain and in the liver. This is a first identification of multiple receptors for a single virus. The presence of different receptors in different tissues may explain the target cell specificity of certain MHVs.
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PMID:Mouse hepatitis virus utilizes two carcinoembryonic antigens as alternative receptors. 132 65

The cellular receptors for a coronavirus, mouse hepatitis virus (MHV), have been recently identified as one or more members of the carcinoembryonic antigen (CEA) family. The neurotropic JHM strain of MHV (MHV-JHM) possesses a highly fusogenic surface (S) glycoprotein. This protein is now shown to promote the spread of MHV into cells lacking the specific CEA-related MHV receptor. Resistant cells are recruited into MHV-induced syncytium with consequent production of progeny virus. Cell-to-cell spread of virus via membrane fusion without the requirement for specific cell surface receptor offers a novel way for virus to spread within infected hosts.
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PMID:Cell receptor-independent infection by a neurotropic murine coronavirus. 141 26

The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.
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PMID:Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. 164 19

The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR1. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR1-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CC1. Thus, the 110- to 120-kDa CEA-related glycoprotein encoded by MHVR1 is a functional receptor for murine coronavirus MHV-A59.
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PMID:Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. 171 35


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