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

The polypeptides encoded in open reading frame (ORF) 1b of the mouse hepatitis virus A59 putative polymerase gene of RNA 1 were identified in the products of in vitro translation of genome RNA. Two antisera directed against fusion proteins containing sequences encoded in portions of the 3'-terminal 2.0 kb of ORF 1b were used to immunoprecipitate p90, p74, p53, p44, and p32 polypeptides. These polypeptides were clearly different in electrophoretic mobility, antiserum reactivity, and partial protease digestion pattern from viral structural proteins and from polypeptides encoded in the 5' end of ORF 1a, previously identified by in vitro translation. The largest of these polypeptides had partial protease digestion patterns similar to those of polypeptides generated by in vitro translation of a synthetic mRNA derived from the 3' end of ORF 1b. The polypeptides encoded in ORF 1b accumulated more slowly during in vitro translation than polypeptides encoded in ORF 1a. This is consistent with the hypothesis that translation of gene A initiates at the 5' end of ORF 1a and that translation of ORF 1b occurs following a frameshift at the ORF 1a-ORF 1b junction. The use of in vitro translation of genome RNA and immunoprecipitation with antisera directed against various regions of the polypeptides encoded in gene A should make it possible to study synthesis and processing of the putative coronavirus polymerase.
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PMID:Identification of polypeptides encoded in open reading frame 1b of the putative polymerase gene of the murine coronavirus mouse hepatitis virus A59. 203 67

Blood-borne type non-A, non-B (NANB) hepatitis-associated microtubular aggregates protein was isolated and partially sequenced. The microtubular aggregates were isolated from the hepatocytes of NANB-infected chimpanzees and were found to have a buoyant density in sucrose solution of 1.21 to 1.23 g/ml. A single protein, recognized by our anti-microtubular aggregates monoclonal antibodies, was found to have an Mr of 44,000 (p44). This p44 protein was not found in uninfected chimpanzees. We determined a partial amino acid sequence for p44, and showed that it has no homology to any known proteins.
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PMID:Isolation and purification of a non-A, non-B hepatitis-associated microtubular aggregates protein. 217 May 69

A 1.7 kb cDNA encoding a novel antigen (p44; apparent Mr 44K) associated with non-A, non-B (NANB) hepatitis, was isolated from the hepatic cDNA library of a chimpanzee infected with NANB hepatitis. The library was screened with a monoclonal antibody against this antigen. The cDNA cloned contained an open reading frame encoding a 444 amino acid protein with an Mr calculated to be 50,468. The cDNA hybridized to a 1.9 kb mRNA obtained from chimpanzee hepatocytes infected with either the NANB or hepatitis delta viruses. It hybridized weakly to mRNA from hepatitis B virus-infected hepatocytes, and not at all to mRNA from normal chimpanzee hepatocytes. Southern blot analysis revealed that p44 is a host protein in chimpanzees, and that an identical gene exists in the human genome.
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PMID:Cloning, sequencing and expression in Escherichia coli of cDNA for a non-A, non-B hepatitis-associated microtubular aggregates protein. 217 May 70

A hepatitis-C-associated microtubular aggregate protein, referred to as p44, has been identified as a cytoplasmic antigen in the hepatocytes of chimpanzees infected with hepatitis C virus. The production of p44 mRNA is markedly induced in the liver of chimpanzees infected with hepatitis C or hepatitis D virus. To examine the mechanism of this induction, we isolated a genomic clone for the human p44 protein and analyzed its structure. The human p44 gene spans approximately 14 kbp of DNA and consists of nine exons separated by eight introns. An interferon-stimulated response element, which confers inducibility by interferon-alpha/beta, was found in the promoter region of the gene. Northern-blot analysis revealed that the human p44 gene is inducible by interferon-alpha/beta, but not by interferon-gamma. Functional analysis demonstrated that the interferon-stimulated response element in the promoter region of the gene mediates the inducibility of the gene by interferon-alpha/beta. Thus, the human p44 gene is a member of the family of interferon-alpha/beta inducible genes. The protein p44 may be one of the mediators involved in the antiviral action of interferon.
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PMID:Induction of the human gene for p44, a hepatitis-C-associated microtubular aggregate protein, by interferon-alpha/beta. 792 11

Hepatitis C virus (HCV) infection causes acute and often also chronic liver disease. Worldwide, prevalence of infection is estimated to exceed that of human immunodeficiency virus infection fourfold. Because of the lack of appropriate animal models, knowledge of interactions between virus and host is still limited. Assumptions regarding pathogenesis or the activation status of innate antiviral host responses, for instance, derive mainly from clinical observations and from expression analyses of selected genes. To obtain a more objective insight into virus-host interrelationships, we used suppression-subtractive hybridization to compare gene expression in HCV-infected and non-HCV-infected liver tissues samples. Four differentially expressed genes were found: (i) the gamma interferon (IFN-gamma)-inducible chemokine IP-10 gene; (ii) the IFN-alpha/beta-inducible antiviral MxA gene; (iii) the gene encoding IFN-alpha/beta-inducible p44, shown to be associated with ultrastructural cytoplasmic entities within hepatocytes of non-A, non-B hepatitis-infected chimpanzees; and (iv) the gene encoding IFN-alpha/beta/gamma-inducible IFI-56K, a protein recently shown to interact with the eukaryotic translation initiation factor eIF-3. Compared to hepatic gene expression in patients with liver diseases unrelated to viral infections, expression in patients with chronic HCV infection was up to 50-fold higher. While in patients with chronic HBV infection IP-10 was slightly activated as well, the IFN-alpha/beta-regulated genes were not. Revealing a dominance of hepatic interferon-regulated processes in chronic HCV infection, data on the enhanced expression of the IFN-gamma regulated IP-10 support earlier findings and may explain the composition of the hepatic cellular infiltrate. The data on enhanced expression of IFN-alpha/beta inducible genes might be germane to therapeutic considerations.
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PMID:Enhanced expression of interferon-regulated genes in the liver of patients with chronic hepatitis C virus infection: detection by suppression-subtractive hybridization. 1115 6

The extracellular signal-regulated (ERK), mitogen-activated protein kinase (p42/p44 MAPK) pathway is up-regulated in hepatocellular carcinoma (HCC). Molecular targeting of this critical mitogenic pathway may have therapeutic potential for the treatment of HCC; however, chemoresistance to long-term therapy may develop. In the present study, we employed small-molecule MAPK kinase (MEK) inhibitors, including U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene] and PD184161 (Neoplasia 8:1-8, 2006), in HepG2 and Hep3B human HCC cell lines to identify potential mechanism(s) of resistance. U0126 dose-dependently suppressed ERK phosphorylation at both 1- and 24-h time points in HepG2 cells, previously shown to be sensitive to growth inhibition by U0126. In contrast, ERK phosphorylation was only decreased at the 1-h time point but not at 24 h in the more resistant Hep3B cells. It is interesting that the lack of prolonged phospho-ERK suppression was associated with MEK hyperphosphorylation in Hep3B cells. Several MEK/ERK pathway intermediates were up-regulated in Hep3B cells; furthermore, transfection of Raf-1 small interfering RNA to suppress MEK/ERK pathway activation sensitized Hep3B cells to U0126. MEK inhibitor resistance was independent of p53 or hepatitis Bx protein status. Finally, we showed that combining two chemically distinct MEK inhibitors enhanced growth inhibition and apoptosis compared with the single agents. Taken together, these results suggest that up-regulated expression or activity of the MEK/ERK pathway contributes to MEK inhibitor resistance in HCC cells. Our findings also provide preclinical evidence suggesting that the status of the MEK/ERK pathway in patients may predict response to MEK/ERK-targeted therapeutics.
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PMID:Resistance to mitogen-activated protein kinase kinase (MEK) inhibitors correlates with up-regulation of the MEK/extracellular signal-regulated kinase pathway in hepatocellular carcinoma cells. 1925 20