Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test whether (HCV) persistence is related to interferon (IFN) hyporesponsiveness, peripheral blood monuclear cells from 29 patients and 11 controls were studied for MxA protein expression. In vitro, only IFN-alpha (P<.001) and interleukin-2 (P<.05) induced MxA protein expression above unstimulated levels. Forty patients were treated with IFN-alpha2b. Patients showed higher basal levels of MxA protein (P<.02) and 2',5'-oligoadenylate synthase (2-5A) activity (P<.05) than controls. During therapy, MxA protein levels (P<.001) and 2-5A activity (P<.05) increased; after 1 month, MxA levels remained high, whereas 2-5A activity declined to initial levels. Increases in MxA were inversely correlated with decreases in serum alanine aminotransferase levels, and MxA induction was greater among virological responders. Thus, the IFN system seems to be activated in chronic HCV infection, but HCV appears to modulate these two components of the IFN system differentially. These results suggest that an inefficient response may contribute to virus persistence and affect the therapeutic outcome.
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PMID:In vivo and in vitro induction of MxA protein in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus. 1039 38

As a part of the defense mechanism of the host to viral infection, interferons induce the transcription of several genes. These interferon-inducible genes contribute to the eradication of the viruses. Whereas some studies suggested the participation of a dsRNA-dependent protein kinase in the host reaction to hepatitis C virus infection, the involvement of other interferon-inducible genes has not been evaluated. Furthermore, there has been no analysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of interferon-inducible genes with a special concern to chronic hepatitis C. A total of 76 liver biopsy samples (28 with chronic hepatitis C, 10 with chronic hepatitis B, 9 with alcoholic liver disease, 14 with autoimmune hepatitis, 10 with primary biliary cirrhosis, and 5 of normal liver) were enrolled. The expression of the following genes was quantified by competitive reverse transcription-polymerase chain reaction and was compared according to the etiology; dsRNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase (2,5-AS), latent cellular endoribonuclease (RNase L), RNase L inhibitor, and MxA. As a result, PKR mRNA was significantly overexpressed in the liver of chronic hepatitis C compared with those of other etiologies (P =.0178), and it correlated significantly with serum alanine transaminase values (r =.51, P =.0054). Also, the expression of the RNase L inhibitor showed a significant reduction in chronic hepatitis C (P =.0184). The expressions of 2,5-AS, RNase L, and MxA were not different significantly irrespective to the etiology. In conclusion, hepatic overexpression of PKR and reduced expression of RNase L inhibitor seem to contribute to the anti-HCV mechanism characteristically.
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PMID:Intrahepatic mRNA expression of interferon-inducible antiviral genes in liver diseases: dsRNA-dependent protein kinase overexpression and RNase L inhibitor suppression in chronic hepatitis C. 1105 60

Hepatitis B is not only a preventable but now treatable disease. Five drugs have been approved for the treatment of chronic hepatitis B virus (HBV) infection: standard interferon-alpha (IFN), pegylated IFN, lamivudine, adefovir dipivoxil and entecavir. Among these agents, the responses to interferon therapy are invariably influenced by both host and viral factors. Therefore, understanding these factors is important for practicing hepatologists, and it may help design individualized medicine for the treatment of chronic hepatitis B. HBV genotypes affect the disease progression and outcomes of HBV-related chronic liver disease, as well as the response to antiviral treatments. Existing data indicate a better sustained response to standard IFN-alpha in HBeAg positive genotype B patients than genotype C patients, and in genotype A patients than genotype D patients. Nevertheless, conflicting results exist regarding the response to pegylated IFN, and more studies are needed. As to HBV genetic polymorphisms, a recent study showed that an IFN sensitivity-determiningregion may not exist within the whole genome of HBV subgenotype Ba, and host factors as well as virus-host interactions may be more important than viral factors alone in determining the treatment outcomes with IFN. Regarding host genetic polymorphisms, single nucleotide polymorphisms within eukaryotic translation initiation factor 2 and MxA promoter regions may be associated with the responsiveness to standard IFN-alpha treatment in patients with HBeAg positive chronic hepatitis B. In the foreseeable future, individualized chronic hepatitis B treatment algorithms should be tailored to host (immune status, ALT level and genomic polymorphisms), virus (HBeAg status, HBV DNA level, genotype, precore/basal core promoter mutants and pre-S deletion mutant) as well as liver disease status (hepatitis activity and fibrosis stage).
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PMID:Appropriate use of interferon for treatment of chronic hepatitis B. 1762 36

Antiviral effect of interferon is mediated by the expression of interferon-stimulated genes (ISGs). However, because of the difficulty in obtaining paired liver biopsies before and after interferon treatment, the key ISGs expressed in human hepatocytes and responsible for interferon-based antiviral activities in chronic hepatitis C remain illusive. Prior to a standard course of peginterferon plus ribavirin therapy, 104 patients underwent a liver biopsy. A small piece of the liver biopsy sample from each patient was submitted for ex vivo tissue culture in the presence or absence of interferon. Hepatic expression of 8 ISGs was detected by RT-PCR. The ISG expression patterns and clinicopathological variables were correlated with subsequent treatment outcomes. Multivariate logistic regression analysis showed that hepatic MxA expression (P = 0.008) and leucocyte count (P = 0.040) independently predicted the end of therapeutic virological response, while hepatic OAS1 expression (P = 0.003), genotype 1 (P = 0.002), HCV-RNA level (P = 0.007), AST/ALT ratio (P = 0.004) and leucocyte count (P = 0.034) independently predicted the sustained virological response. Immunohistochemistry analysis showed that interferon-induced OAS1 expression localized to the hepatocytes. In conclusion, hepatic MxA and OAS1 expression predicted, respectively, the end of therapeutic and sustained virological responses in interferon-based treatment of chronic hepatitis C.
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PMID:Hepatic expression of MxA and OAS1 in an ex vivo liver slice assay independently predicts treatment outcomes in chronic hepatitis C. 2223 13

CpG oligodeoxynucleotides (ODNs) stimulate immune cells via TLR9 and are potentially useful immunomodulators for the treatment of chronic viral infections. In the present study, different classes of CpGs were tested for their capacities for innate immune activation and antiviral activities in the woodchuck model. A class P CpG ODN was found to stimulate interferon (IFN) production in woodchuck peripheral blood mononuclear cells (PBMCs) in vitro, and following subcutaneous administration in vivo, it was observed to induce IFN and MxA expression in woodchuck PBMCs. Combination treatment with CpG ODN and entecavir (ETV) led to effective suppression of the woodchuck hepatitis virus (WHV) load in the woodchucks, with early viral responses and inhibition of replication. The woodchuck hepatitis surface antigen (WHsAg) serum concentrations were strongly decreased by CpG and ETV together but not by either agent alone, indicating synergistic effects. However, viral control post-treatment was still transient, similar to that observed with ETV alone. Significantly elevated levels of serum aspartate aminotransferase (AST) but not of alanine aminotransferase (ALT) in some of the woodchucks receiving CpG ODN were noted, but these increases were resolved before the completion of treatment and were not associated with an elevated serum bilirubin level or coagulation disorders, suggesting the absence of a significant safety concern.
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PMID:Combination therapy including CpG oligodeoxynucleotides and entecavir induces early viral response and enhanced inhibition of viral replication in a woodchuck model of chronic hepadnaviral infection. 2658 44