Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight patients with chronic hepatitis B infection (seven with chronic active hepatitis and one with chronic persistent hepatitis) were treated with daily intramuscular injections of human leucocyte interferon for periods of 5 to 8 weeks and in one case for 5 months. In one patient there was a marked fall in virus-associated DNA polymerase activity and in the number of DNA containing viral particles during each of two courses of interferon. Hepatitis Be antigen (HBeAg) also disappeared, the aspartate transaminase levels fell and liver histology improved. In the four other patients with detectable DNA polymerase activity there was an early fall but this was transient and in one of these patients there was a continuing rise in activity despite treatment. One other patient became HBeAg negative but hepatitis B surface antigen (HBsAg) titres were mostly unaffected by treatment. A marked decrease in T-lymphocyte mediated cytotoxicity towards HBsAg coated target cells was demonstrated and raises the possibility that an immunosuppressant action of interferon may offsets its direct anti-viral action but may also account for the improvement in liver function which occurred in some patients.
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PMID:Effects of human leucocyte interferon on hepatitis B virus replication and immune responses in patients with chronic hepatitis B infection. 50 26

To identify factors predicting response to antiviral therapy, we reviewed the clinical features of 38 male hepatitis B surface antigen (HBsAg) carriers who received adenine arabinoside or lymphoblastoid interferon. All patients were followed for one year or longer. Response was defined as loss of hepatitis B e antigen, hepatitis B virus DNA and DNA polymerase from the serum. Only 2 of 19 (11%) homosexual men responded, compared with 10 of 19 (53%) heterosexual men (P less than 0.02). Both responders in the homosexual group had received lymphoblastoid interferon. None of the 13 homosexual men, but 8 of 16 heterosexual men, responded to adenine arabinoside or its monophosphate (P less than 0.01). Responders to antiviral therapy had higher (P less than 0.05) serum levels of aspartate aminotransferase (median 115, range 51-344) than did non-responders (median 83, range 32-181). The decreased responsiveness of homosexual men to antiviral therapy may be a result of more severe immunologic abnormalities in homosexual than in heterosexual men with HBsAg-positive chronic liver disease.
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PMID:Diminished responsiveness of homosexual men to antiviral therapy for HBsAg-positive chronic liver disease. 241 58

Twenty patients with HBe antigen positive, chronic active hepatitis receiving interferon-beta (HuIFN-beta) for 4 weeks were studied. Within the follow-up period (12.3 +/- 2.0 months; mean +/- SD), nine patients were seroconverted to anti-HBe positive and/or HBe antigen negative. In vitro synthesis of interleukin-1 (IL-1), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined from supernatants of peripheral blood mononuclear cells (PBMCs) cultured in the presence of lipopolysaccharide or concanavalin-A. PBMCs from patients before IFN-beta treatment secreted markedly reduced levels of IL-1 (p less than 0.01) and IFN-gamma (p less than 0.01) as compared with healthy controls. However, IFN-gamma synthesis in the patients was significantly increased (p less than 0.05) along with the IFN-beta treatment. IL-2 synthesis was similar in chronic active hepatitis B patients before and during IFN-beta treatment when compared to normal controls, but after the therapy, the elevation of IL-2 synthesis was observed in accordance with the elevation of serum AST in two cases. Nine patients who seroconverted to anti-HBe positive and/or HBe antigen negative showed the significantly lower levels of DNA polymerase before IFN-beta treatment than non-responder group. There were no other differences in sex, age, serum AST, histologic activities and cytokine production in vitro between two groups. These results indicate the presence of immunologic deficiencies in patients with HBe antigen positive chronic active hepatitis and give the rationales for the use of interferon treatment on immunologic basis.
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PMID:[In vitro cytokine production in patients with HBe antigen positive chronic active hepatitis receiving interferon-beta]. 250 83

Seven children with chronic active hepatitis (CAH) and one child with persistently abnormal results of liver function test due to hepatitis B virus (HBV) infection were treated with human leukocyte interferon (Hu-alpha-IFN). Five of them were positive for eAg and two of the three who were measured for DNA polymerase (DNAP) activity in sera showed moderate elevations of its levels. Hu-alpha-IFN was injected intramuscularly daily or once weekly at doses of 0.05-1 X 10(6) IU. The total dose per patient varied from 10.5-54 X 10(6) IU. After administration of Hu-alpha-IFN, rapid loss of eAg was observed in two of the five eAg patients, and DNAP activity reverted to normal ranges in the two patients with moderate elevations of its levels. One of the patients who lost eAg has retained normal serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels for more than 2 years after therapy with Hu-alpha-IFN. Serial hepatic biopsies were performed in only one patient. In the second biopsy, 3 months after therapy with Hu-alpha-IFN, infiltration of inflammatory cells in the portal region was improved compared with earlier findings. Immediate and/or prolonged adverse side effects were not observed during or after administration of Hu-alpha-IFN. For the present, we propose these six conditions for use of Hu-alpha-IFN in children with HBV infection. Children should: (a) be more than 1 year old; (b) have abnormal liver function for more than 6 months; (c) have a liver biopsy demonstrating CAH; (d) have moderate elevation of DNAP activity; (e) be eAg positive; and (f) be unresponsive to other treatments.
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PMID:Therapeutic effects of human leukocyte interferon on chronic active hepatitis B in children. 398 64

A controlled trial has been undertaken to evaluate adenine arabinoside in the treatment of hepatitis B surface antigen-positive chronic liver disease. Thirteen patients (7 hepatitis B virus DNA polymerase and hepatitis B e antigen-positive, 6 DNA polymerase negative and hepatitis B e antibody-positive) were treated with adenine arabinoside. Eleven comparable patients served as controls, and follow-up was for 6 mo. In the 7 hepatitis B e antigen-positive patients, adenine arabinoside produced a fall in DNA polymerase activity during treatment. When this effect was sustained, it was followed by a loss of e antigen (3 patients). Hepatitis B surface antigen concentrations and aspartate transaminase levels fell significantly at 6 mo (p less than 0.05) in the treated group compared with controls. In the hepatitis B e antibody-positive patients, adenine arabinoside treatment produced no significant change in hepatitis B surface antigen concentrations or aspartate transaminase levels at 6 mo as compared with controls. Adenine arabinoside would appear to reduce either transiently or permanently, hepatitis B virus replication, and it may therefore be useful in reducing the infectivity of some carriers of this virus. In the dose used, adenine arabinoside was ineffective in clearing hepatitis B surface antigen from the serum and eradicating hepatitis B virus from the liver, but combination with other antiviral or immunostimulant agents may enhance its therapeutic effectiveness.
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PMID:Adenine arabinoside therapy in HBsAg-positive chronic liver disease: a controlled study. 700 10

Changes in markers of hepatitis B viral replication and standard liver function tests were studied in 30 patients with HBsAg positive chronic liver disease starting or stopping prednisolone/azathioprine therapy, and compared with those occurring in 15 patients who did not receive therapy. On stopping prednisolone/azathioprine, 10 out of 11 HBeAg positive patients and one out of three patients negative for HBeAg and anti-HBe, lost HBV-DNA polymerase activity (p less than 0.01), five lost HBeAg, three developed anti-HBe and HBsAg concentration decreased (p less than 0.01). Only one out of seven untreated HBeAg positive patients lost HBeAg and there were no significant changes in DNA polymerase activity. In the anti-HBe positive patients, 14 starting therapy and eight untreated, there were no significant changes in the markers of viral replication - although two patients developed DNA polymerase activity on high maintenance doses of prednisolone - but a significant decrease (p less than 0.05) in aspartate transaminase in the treated group. It is concluded that the cessation of prednisolone/azathioprine therapy in HBeAg positive patients will result in a reduction in viral replication. In anti-HBe positive patients such therapy may be beneficial.
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PMID:Effects of prednisolone/azathioprine in chronic hepatitis B viral infection. 709 59

Hepatitis B virus associated DNA polymerase activity, hepatitis b surface antigen (HBsAg), and serum aspartate aminotransferase were followed in 21 patients with chronic active hepatitis while immunosuppressive therapy (prednisone +/- azathioprine) was being withdrawn. In every case, DNA polymerase activity fell within 6-10 wk of decreasing treatment and became undetectable in 8 patients. This was usually accompanied by a fall in HbsAg titer and a transient rise in serum aspartate aminotransferase activity. Four additional patients with previously untreated HbsAg positive chronic active hepatitis were placed on prednisone for 12 wk. There was a rise in DNA polymerase activity and HBsAg titer with a fall in serum aspartate aminotransferase values during treatment. Upon discontinuing therapy, DNa polymerase activity fell dramatically in all 3 patients who completed their course of prednisone and became undetectable in 1. These findings suggest that immunosuppressive therapy has a potentiating effect on hepatitis B viral replication in patients with chronic active hepatitis.
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PMID:Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. 728 93

To assess which residues of Oct-1 POU-specific (POUs) are important for DNA recognition and stimulation of adenovirus DNA replication we have mutated 10 residues of the POUs helix-turn-helix motif implicated in DNA contact. Seven of these turned out to have reduced DNA binding affinity. Of these, three alanine substituted proteins were found to have a changed specificity using a binding site selection procedure. Mutation of the first residue in the recognition helix, Gln44, to alanine led to a loss of specificity for the first two bases, TA, of the wild-type recognition site TATGC(A/T)AAT. Instead of the A, a T was selected, suggesting a new contact and a novel specificity. A change in specificity was also observed for the T45A mutant, which could bind to TATAC(A/T)AAT, a site hardly recognized by the wild-type protein. Mutation of residue Arg49 led to a relaxed specificity for three consecutive bases, TGC. This residue, which is critical for high affinity binding, is absent from the structurally homologous lambdoid helix-turn-helix motifs. Employing a reconstituted system all but two mutants could stimulate adenovirus DNA replication upon saturation. Mutation of residues Gln27 and Arg49 impairs the ability of the Oct-1 POU domain protein to enhance replication, with a concomitant loss of DNA contacts. Since the POU domain binds the precursor terminal protein-DNA polymerase complex and guides it to the origin, lack of stimulation may be caused by incorrect targetting of the DNA polymerase due to loss of specificity.
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PMID:Mutation of the Oct-1 POU-specific recognition helix leads to altered DNA binding and influences enhancement of adenovirus DNA replication. 766 96

Interferon-alpha induces remission in 30% to 40% of patients with chronic hepatitis B, but its effect on hepatic connective tissue turnover has not been well documented. We studied the changes in serum procollagen III propeptide and laminin-P1 peptide (Lam-P1) in 33 patients with chronic hepatitis B (11 nontreated controls and 22 treated patients) during a 4-mo randomized trial of interferon-alpha. Liver biopsy specimens were obtained at the start of treatment and 12 mo later. Liver biochemical tests, procollagen III propeptide, laminin-P1 peptide and hepatitis B virus DNA polymerase were determined before treatment with interferon was begun (mo -3), at the initiation (0 time) and completion of treatment (mo 4) and also at 8, 12 and 18 mo. Treated patients were classified as "responders" and "nonresponders" on the basis of clearance of HBV e antigen from serum. There were no significant changes in the control group, whereas the responders had persistent decreases in ALT, AST, hepatitis B virus dna polymerase, procollagen III propeptide and laminin-P1 peptide. The nonresponders had transient ALT, AST and hepatitis B virus dna polymerase reductions that returned toward baseline levels during follow-up, but procollagen III propeptide and laminin-P1 peptide persisted below the baseline at mo 18. Significant correlations between procollagen III propeptide and laminin-P1 peptide with ALT, AST and liver histologic specimens were noted at baseline but not after 12 mo. Changes in procollagen III propeptide levels also correlated with changes in AST, ALT and liver histologic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in serum levels of markers of hepatic connective tissue turnover during and after treatment of chronic hepatitis B with interferon-alpha. 813 56

Interferon-alpha therapy leads to HBeAg seroconversion in only one third of patients with chronic hepatitis B. In an attempt to increase the seroconversion rate, we investigated the combination of interferon-alpha and zidovudine in a subset of patients with presumably low response rates for interferon-alpha monotherapy. In a double-blind, controlled trial, 24 HBeAg-positive patients were randomized to receive lymphoblastoid interferon-alpha in subcutaneous doses increasing to 5 MU daily, combined with zidovudine given orally in doses increasing from 500 to 1,000 mg/day or with placebo for 16 wk. Treatment effects were monitored by quantitative assessment of HBV DNA, HBeAg and HBV DNA polymerase. Six months after termination of therapy, 1 of 12 (8%; 95% confidence interval = 2% to 39%) patients treated with interferon-alpha plus zidovudine and 2 of 12 (17%; 95% confidence interval 2% to 48%) patients from the control group exhibited responses (HBeAg seroconversion). All patients remained HBsAg positive. The only responder of the interferon-alpha-zidovudine group relapsed after cessation of therapy, so none of the zidovudine-treated patients were HBeAg negative at the end of follow-up. No significant difference in AST level or in any of the virological markers was observed between the two groups during the course of the study. Adverse effects (anemia, leukopenia) necessitated reduction in the dose of zidovudine in 50% and of interferon-alpha in 42% of the patients treated with interferon-alpha plus zidovudine; in the control group these rates were 0% for placebo and 8% for interferon-alpha. In conclusion, the antiviral effect of interferon-alpha in chronic hepatitis B was not enhanced by additional zidovudine treatment. The combination therapy induced considerable side effects leading to dose reduction for both zidovudine and interferon-alpha. For combination therapy with interferon-alpha, oral nucleoside analogs with more potent antiviral effects and less toxicity than zidovudine should be developed.
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PMID:Interferon-alpha and zidovudine combination therapy for chronic hepatitis B: results of a randomized, placebo-controlled trial. 844 11


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