Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biliary glycoprotein (BGP) isoantigens are derived by alternative splicing from a single gene and are the human homologs of rat C-CAM and the mouse Bgp species. These glycoproteins represent a family of cell-adhesion molecules. The mouse Bgp isoforms also act as receptors for the hepatitis viral capsid-protein. BGP is a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin supergene family, yet it displays restricted expression patterns and unique functions. Since the loss or reduced expression of BGP is associated with human colorectal carcinomas, the elements in its upstream regulatory region were analyzed. A cluster of transcriptional initiation sites and the minimal promoter, located within 150 bp upstream of the major transcriptional start site, were active in human colon carcinoma and hepatoma cells. Unlike the CEA gene, BGP gene transcription was not modulated by a silencer region; repetitive elements in the BGP upstream region were not involved in activation or repression. Footprinting experiments identified two cis-acting elements and mobility-shift assays demonstrated that these elements bound several transcription factors, among them, USF, HNF-4 and an AP-2-like factor. In cotransfection experiments, both the USF and HNF-4 transcription factors transactivate the BGP gene promoter and compete for the same regulatory element. The Sp1 transcription factor, shown to be involved in CEA gene transcriptional regulation, does not bind to the BGP gene promoter. We, therefore, propose that the relative distributions and interactions of these transcription factors mediate distinct transcriptional regulation of the BGP gene in colon and liver; this regulation could be distorted during the oncogenic process.
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PMID:Transcriptional control of the human biliary glycoprotein gene, a CEA gene family member down-regulated in colorectal carcinomas. 805 23

The expression of carcinoembryonic antigen (CEA)-related glycoproteins that have been associated with intercellular adhesion and that serve as receptors for mouse hepatitis virus (MHV) was analyzed in cells from the immune system of BALB/c mice using immunolabeling and RNA polymerase chain reaction amplification of receptor transcripts. These glycoproteins, which are called biliary glycoproteins, were highly expressed in B lymphocytes, including cells of the B-1a (CD5+) lineage, and in macrophages, but were not detectable in resting T lymphocytes. Similarly, murine cell lines of B cell and macrophage origin expressed messenger RNA encoding CEA-related molecules, while the corresponding mRNA was only slightly detectable in a T cell line. These CEA-related cell adhesion glycoproteins were also expressed in endothelial cells. Therefore, their specific interaction with their so far unknown ligand may be of functional importance in cellular interactions in the immune response. Monoclonal antibody directed against these glycoproteins blocked MHV-A59 infection of the B cell-derived SP20 cell line. Thus, the functional receptors for MHV on B lymphocytes, like those on murine fibroblasts, are isoforms of CEA-related glycoproteins. Treatment of B cells with anti-receptor antibody also blocked B cell-mediated cytotoxicity against MHV-A59-infected fibroblasts, indicating that this phenomenon is mediated by interaction of viral attachment protein on the infected target cells with specific CEA-related receptor glycoproteins on the effector B cells.
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PMID:B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. 820 98

Murine coronaviruses such as mouse hepatitis virus (MHV) infect mouse cells via cellular receptors that are isoforms of biliary glycoprotein (Bgp) of the carcinoembryonic antigen gene family (G. S. Dveksler, C. W. Dieffenbach, C. B. Cardellichio, K. McCuaig, M. N. Pensiero, G.-S. Jiang, N. Beauchemin, and K. V. Holmes, J. Virol. 67:1-8, 1993). The Bgp isoforms are generated through alternative splicing of the mouse Bgp1 gene that has two allelic forms called MHVR (or mmCGM1), expressed in MHV-susceptible mouse strains, and mmCGM2, expressed in SJL/J mice, which are resistant to MHV. We here report the cloning and characterization of a new Bgp-related gene designated Bgp2. The Bgp2 cDNA allowed the prediction of a 271-amino-acid glycoprotein with two immunoglobulin domains, a transmembrane, and a putative cytoplasmic tail. There is considerable divergence in the amino acid sequences of the N-terminal domains of the proteins coded by the Bgp1 gene from that of the Bgp2-encoded protein. RNase protection assays and RNA PCR showed that Bgp2 was expressed in BALB/c kidney, colon, and brain tissue, in SJL/J colon and liver tissue, in BALB/c and CD1 spleen tissue, in C3H macrophages, and in mouse rectal carcinoma CMT-93 cells. When Bgp2-transfected hamster cells were challenged with MHV-A59, MHV-JHM, or MHV-3, the Bgp2-encoded protein served as a functional MHV receptor, although with a lower efficiency than that of the MHVR glycoprotein. The Bgp2-mediated virus infection could not be inhibited by monoclonal antibody CC1 that is specific for the N-terminal domain of MHVR. Although CMT-93 cells express both MHVR and Bgp2, infection with the three strains of MHV was blocked by pretreatment with monoclonal antibody CC1, suggesting that MHVR was the only functional receptor in these cells. Thus, a novel murine Bgp gene has been identified that can be coexpressed in inbred mice with the Bgp1 glycoproteins and that can serve as a receptor for MHV strains when expressed in transfected hamster cells.
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PMID:Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses. 820 27

Previous studies have shown that some mouse strains are resistant to mouse hepatitis virus (MHV) infection despite the presence of functional viral receptors (K. Yokomori and M. M. C. Lai, J. Virol. 66, 6931-6938, 1992). To determine the molecular requirement for MHV infection, several cell lines derived from both susceptible and resistant mouse strains were tested for their ability to support infection by two different MHV strains, JHM and A59. Most of the cell lines tested, including ones from susceptible mouse strains, exhibited selective resistance to JHM, but were susceptible to A59, suggesting that there is an additional cellular factor(s) discriminating JHM from A59 infection. Both RNA and protein syntheses of JHM were inhibited in the resistant cells; however, transfection of JHM genomic RNA into these cells led to the production of infectious virus, suggesting that the restriction step(s) is during an early stage of viral replication cycle. The mRNA for the MHV receptor (the murine homolog of the carcinoembryonic antigen) is expressed in all cell lines, and expression in COS cells of the receptor isolated from the resistant murine cell lines rendered the COS cells susceptible to both A59 and JHM infections. Furthermore, the transfection of additional MHV receptors into the resistant cells did not overcome the resistance to JHM virus infection. These results suggested that the viral receptor is functional; nevertheless, the JHM infection is restricted at an early step of infection in these cells. The study of the growth properties of the various recombinant viruses between A59 and JHM revealed that one of the viral genes determining viral replication in these cell lines is the S protein gene; thus, the second factor required for viral infection may interact directly or indirectly with the S protein at an early step of infection. Taken together, these studies suggest that expression of a functional viral receptor is not sufficient to establish MHV infection, and that an additional factor(s) is required for an early step of viral infection, possibly during virus entry.
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PMID:A spike protein-dependent cellular factor other than the viral receptor is required for mouse hepatitis virus entry. 839 26

Mouse biliary glycoprotein (Bgp) is a member of the carcinoembryonic antigen gene family and is highly expressed in the epithelial cells of normal hepatic biliary ducts and intestine. Nine mouse Bgp isoforms have been identified through molecular cloning and shown to be splice and allelic variants of one Bgp gene. These glycoproteins function in vitro as intercellular adhesion molecules and serve as the mouse hepatitis virus receptors. Since human carcinoembryonic antigen is overexpressed in gastrointestinal tumors, we have investigated the expression of mouse Bgp in primary tumors and carcinoma cell lines. Our results demonstrate that the expression of the major mouse Bgp isoforms is down-regulated in tumors at the transcriptional and the posttranscriptional levels. This decrease in expression is corroborated by immunostaining of primary colonic tumors with anti-mouse Bgp antibodies. In addition, Bgp expression is influenced by transcriptional control mechanisms involving DNA methylation of the Bgp gene upstream regulatory region. Our results demonstrate that mouse Bgp protein expression is decreased upon malignant transformation and further suggest that Bgp proteins may be involved in the maintenance of the differentiated cellular phenotype.
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PMID:The expression of mouse biliary glycoprotein, a carcinoembryonic antigen-related gene, is down-regulated in malignant mouse tissues. 840 84

Biliary glycoproteins (BGPs) are members of the carcinoembryonic antigen (CEA) family. These glycoproteins function in vitro as intercellular adhesion molecules and, in vitro as intercellular adhesion molecules and, in the mouse, serve as receptors for the mouse hepatitis viruses. In previous studies, BGP expression has been reported to be generally downregulated in colon and liver carcinomas of human, rat and mouse origins. We now demonstrate that introduction of murine Bgp1 cDNA isoforms into a mouse colonic carcinoma cell line, negative for endogenous Bgpl expression, significantly alters the growth properties of these cells. Cells bearing two Bgp1 isoforms were growth-retarded and exhibited a reduced ability to form colonies in an in vitro transformation assay, when compared to parental or control neor cells. Furthermore, tumor formation was inhibited by 80% when cells bearing a full-length Bgp1 isoform were injected into BALB/c syngeneic mice, while cells expressing a Bgp1 isoform lacking most of the intracytoplasmic domain produced tumors as readily as the parental cells. There results indicate that a biliary glycoprotein isoform is involved in negative regulation of colonic tumor cell growth, by a process which requires its intracytoplasmic domain. The precise mechanisms causing Bgp-dependent tumor growth inhibition remain, however, to be defined.
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PMID:Inhibition of colonic tumor cell growth by biliary glycoprotein. 857 Jan 89

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100-120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5-15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia < 2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intra-arterial chemotherapy in patients with unresectable hepatic tumors.
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PMID:Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases. 872 14

The mouse hepatitis virus (MHV) spike glycoprotein mediates attachment of the virus to the MHV receptor, the murine biliary glycoprotein (BGP) carcinoembryonic antigen. Monoclonal antibody CC1 directed against BGP specifically inhibited infection of DBT, Sac-, GT1-7, and OBL21 cells by wild-type MHV-4 and the neuron-adapted variant OBLV60. Binding to this receptor was necessary to establish infection by cell-free MHV; however, the presence of BGP was not required for infection by cell-associated virus. Cell-associated infectious induced syncytium formation on Vero and BHK cells, which lack murine BGP; this activity was not inhibited by monoclonal antibody CC1. Antibody CC1 also did not prevent syncytium formation on DBT cells, which bear BGP. In infectious center assays, the MHV-4 variant OBLV60, which exhibits acid-dependent fusion, spread to cells lacking BGP only when exposed to acidic media. Therefore, spike-mediated fusion was required for BGP-independent spread of MHV infection. Furthermore, BGP-independent, cell-associated spread of MHV-4 was prevented by monoclonal antibodies 5A13.5 and 5B19.2 directed against the spike glycoprotein, but not by other neutralizing and nonneutralizing anti-spike antibodies. Expression of spike glycoprotein by recombinant vaccinia virus resulted in fusion of BGP-negative cells; monoclonal antibodies 5A13.5 and 5B19.2 strongly inhibited spike-mediated fusion in this assay.
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PMID:Spike glycoprotein-mediated fusion in biliary glycoprotein-independent cell-associated spread of mouse hepatitis virus infection. 880 41

Several splice variants of the murine biliary glycoprotein 1 (Bgp 1) gene in the carcinoembryonic antigen gene superfamily serve as cellular receptors for mouse hepatitis virus. RNAPCR and immunoblot analysis of the receptor in inbred mouse strains showed that the glycoproteins expressed in SJL/J mice are encoded by an allelic variant of the Bgp 1 gene, named Bgp 1b. We recently cloned and characterized a second gene, Bgp 2, that encodes a functional MHV receptor glycoprotein which is not recognized by anti-MHVR MAb-CC1. A third gene related to Bgp 1 was cloned and expressed and shown to encode a soluble protein called Cea-10 that differs significantly in its N-terminal domain from Bgp 1 and Bgp 2. Chimeric proteins constructed between the different murine Bgps and point mutations in the prototype MHV receptor, Bgp 1a or MHVR, were analyzed to further characterize the MAb-CC1-binding and virus-binding domains within the N terminal domain of the receptor. Thus, the murine host for MHV expresses multiple splice variants of mRNAs encoded by several different Bgp-related genes which differ in their ability to serve as MHV receptors. The differential expression of these genes in different murine tissues may help to explain the tissue tropism of MHV strains.
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PMID:Characterization of a new gene that encodes a functional MHV receptor and progress in the identification of the virus-binding site(s). 883 May 5

We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in our subjects, who had primary liver cancer and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant type (resembles CC 34%). The separated and HCC-predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.
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PMID:A clinicopathological study on combined hepatocellular and cholangiocarcinoma. 887 74


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