Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duck hepatitis B virus (DHBV) shows clear age-dependent infectious patterns like that of Hepatitis B virus, and many factors have been assumed to have a role in the persistence of the infection. In the present study, the activities of the interferon-induced enzyme 2',5' oligoadenylate synthetase (2,5AS) were observed sequentially in the serum of ducks experimentally infected with DHBV on posthatch days 1, 7 and 14. These were compared with the infectious pattern to investigate whether the endogenous interferon response after infection in ducks of different ages has a major role in its determination. The infectious pattern of DHBV in 1-day-old ducks was persistent without hepatitis and the others were transient with hepatitis. Persistently infected ducks showed significantly lower activities of 2,5AS compared with those with transient hepatitis, which resulted in a rapid elimination of DHBV. Although 1-day-old ducks showed significantly high 2,5AS compared with non-infected ducks, interferon response alone appeared to be insufficient for the elimination of DHBV. The immune response seemed necessary for the complete elimination of DHBV by way of evoking hepatitis and stimulating more interferon response during the usual infectious course. The interferon system alone did not seem to have a critical role in determining the infectious pattern. Other factors, including the immune response to the virus, seemed to have a major role in this problem.
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PMID:The sequential change of serum 2',5' oligoadenylate synthetase in different infectious patterns of duck hepatitis B virus in ducks in experimental transmission. 137 31

Ninety per cent of patients infected in adult life with the hepatitis B virus clear the virus completely and 10% develop chronic infection. There is evidence for the involvement of interferon in the clearance of acute hepatitis B virus infection. We report that, in in vitro tests, some hepatitis B virus carriers have a reduced capacity to produce alpha- and gamma-interferon which is unrelated to the level of viral replication and to the severity of the liver disease and that the level of 2-5 oligoadenylate synthetase in their livers is only minimally elevated compared to controls. Treatment with lymphoblastoid (alpha-) interferon leads to a marked rise in 2-5 oligoadenylate synthetase activity. These data indicate that some patients with chronic hepatitis B virus infection acquired in adult life have a partial deficiency of production of alpha-interferon but can respond to exogenous alpha-interferon. These observations provide a logical basis for attempts to treat this condition with interferons.
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PMID:Evidence for a deficiency of interferon production in patients with chronic hepatitis B virus infection acquired in adult life. 242 24

Immune function was assessed in 93 adult hemophiliacs in the 2 years prior to HTLV-III antibody testing of blood donors and routine heat treatment of coagulation factor concentrates. Parameters of humoral and cellular immunity studied included serum complements, immunoglobulins, immune complexes, blood cell counts, lymphocyte subsets, lymphocyte transformation, 2-5A synthetase, serology for HTLV-III and hepatitis B, skin tests, and clinical status. HTLV-III seropositivity was significantly more prevalent in patients treated with factor VIII concentrate; seropositive patients had a higher proportion of abnormal test results and were more symptomatic. Although many subjects had abnormal test results, specific test results generally did not correlate with type of blood component received or time of preceding treatment. The proportion of tests abnormal in individual patients was correlated with the intensity of factor replacement therapy when the time interval from the last treatment was a covariate. While T8+ lymphocytes were increased and T4/T8 ratios were decreased in many patients, significantly reduced T4+ lymphocytes were seen only in seropositive patients and in those treated with factor VIII concentrate. Neither seropositivity nor presence of symptoms correlated with abnormal lymphocyte mitogenic response or 2-5A synthetase levels, but synthetase levels were increased in 65% of patients tested. Over the 2-year study period, no significant deterioration of clinical or laboratory variables was observed in the patients. Abnormalities of immune function were found to be common in hemophiliacs regardless of type of treatment or of evidence of HTLV-III infection.
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PMID:Humoral and cellular immune abnormalities in adult hemophiliacs followed over a 2-year period. 243 26

Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via an asialoglycoprotein receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein having a single asparagine-linked sugar chain. Although natural human interferon-beta may also be metabolized through this pathway, there is very little information about the biologic features of human asialointerferon-beta. We evaluated the pharmacokinetics and biologic activities of human native and asialointerferon-beta s. After intravenous administration to rabbits, human asialointerferon-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the liver than the native type, but it induced less 2'5'-oligoadenylate synthetase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B virus-transfected HuH6 cell line, HB611, revealed that the inhibition of hepatitis B virus DNA replication by the asialoprotein was weaker than that by the native protein. The results showed that the different effects exerted by the human native and asialointerferon-beta s may be a result of recognition of the sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pharmacokinetics and biologic activities.
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PMID:Pharmacokinetics and biologic activities of human native and asialointerferon-beta s. 764 42

In the 35 years since the discovery of interferon, significant biological activity has been described for interferon-alpha (IFN alpha) in various cancers, particularly haematological malignancies such as hairy cell leukaemia and chronic myelogenous leukaemia. Except for localised therapy in bladder and ovarian cancer, activity against most solid tumours has been disappointing. Other notable exceptions include Kaposi's sarcoma, renal cell carcinoma and malignant melanoma, tumours known to be susceptible to immunological attack. More recently, broad spectrum antiviral activity has been demonstrated for both recombinant and naturally occurring IFN alpha. Hepatitis C is responsive to IFN alpha in about 40% of patients, but long term remissions are rare. In contrast, long term suppression of hepatitis B is common following IFN alpha therapy. Both diseases respond in a dose proportional fashion, with daily doses of 5 million units (MU) significantly more effective than lower doses. The mechanism of action in viral diseases involves the expression of unique antiviral proteins such as endonuclease and 2'-5'-oligoadenylate synthetase which enhance the destruction of viral RNA. General cellular protein synthesis is also inhibited, including cytochrome P450 enzymes. This forms the basis for potential drug interactions, with IFN alpha slowing the clearance of highly metabolised drugs such as theophylline. As an antitumour agent, the mechanism of action of IFN alpha is unclear, particularly in haematological cancers. In melanoma and renal cell carcinoma, antitumour effects may be mediated by augmented immune responses including activation of natural killer lymphocytes and enhanced expression of cell surface antigens (e.g. MHC I and II). Conversely, antibody formation to recombinant IFN alpha may result in a loss of activity. This has been observed in both renal cell cancer and hepatitis B and C. The elimination half-life of IFN alpha is short, 4 to 5 hours, but biological activity extends for 2 to 3 days after administration, which facilitates daily or thrice weekly administration. Clearance of IFN alpha is mediated by catabolism in the renal tubules; no intact drug is excreted in the urine. It is probable that the antiviral indications of IFN alpha will expand as the agent is more clearly recognised as a primary endogenous defence against various viral conditions.
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PMID:Interferon-alpha in malignant and viral diseases. A review. 768 71

We have investigated the relation between acute-like transaminase exacerbations and the induction of 2',5'-oligoadenylate (2-5A) synthetase activity, HLA-I associated beta 2-microglobulin and macrophage activated release of neopterin during hepatitis B virus clearance in 70 patients treated or not with interferon. In treated patients who had an exacerbation in ALT during HBV clearance (loss of HBeAg and HBV-DNA from serum), the activity of the enzyme 2-5A synthetase and the level of beta 2 microglobulin increased markedly (p < 0.05). In contrast, in the absence of a peak in ALT during HBV clearance following interferon administration, the levels of 2-5A synthetase activity and neopterin, but not of beta 2-microglobulin, rose significantly (p < 0.05). Neither the non-responder treated patients nor the untreated controls had significant changes in these parameters, irrespective of the transaminase levels. Thus, elimination of viremia after interferon treatment may occur by different pathways as reflected by the presence or absence of acute-like biochemical exacerbations.
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PMID:[Changes in serum levels of beta 2-microglobulin, neopterin and 2',5'-oligoadenylate synthase activity during clearance of hepatitis B virus with or without acute phase in transaminases]. 768 94

The relationship between 2', 5'-oligoadenylate synthetase (2-5AS) and HLA class I antigen in the hepatocyte of patients with type B or type C chronic hepatitis with and without interferon (IFN) therapy was investigated. The expression of HLA class I antigen of hepatocytes of biopsied specimen and PBL HLA class I antigen expression showed relevancy. Then, the HLA antigen expression of peripheral blood lymphocyte (PBL) and the 2-5AS activity of peripheral blood mononuclear cell (PBMC) were analyzed. In patients with type B or type C hepatitis, the mean activity of PBMC 2-5AS was significantly higher than that of healthy controls. Also the HLA class I antigen expression of PBL was significantly intense in patients with type B or type C hepatitis compared with healthy controls. In the acute exacerbated phase of type B chronic hepatitis, the HLA class I antigen expression of PBL and 2-5AS activity of PBMC increased along with elevation of serum GPT and then decreased with the remission of serum GPT. These results suggest that endogenously produced IFN leads the lysis of hepatocyte infected with hepatitis B virus (HBV) by cytotoxic T cells, and the restriction of HBV replication by activation of the 2-5A system simultaneously, and then leads the elimination of HBV. The activity of PBMC 2-5AS and the expression of PBL HLA class I antigen increased significantly during IFN therapy. In type B chronic hepatitis, the effective cases showed relatively high activity of serum 2-5AS compared with the non-effective cases. On the other hand, there were no significant differences in PBL HLA class I antigen expression between effective cases and non-effective cases. In type C chronic hepatitis, most patients with type III and type IV HCV genotype showed disappearance of HCV-RNA regardless of serum 2-5AS activity. In patients with type II HCV genotype, the serum 2-5AS activity was related to the anti-viral effect of IFN therapy.
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PMID:[Mechanisms of the effect of interferon (IFN) therapy in patients with type B and C chronic hepatitis]. 768 26

Activation of the arachidonic acid metabolism seems to be one of the post-receptor mechanisms by which interferon-alpha induces antiviral protein synthesis. In this study, we evaluated the changes on serum 2'5'-oligoadenylate synthetase levels induced by acute administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin in 21 patients with hepatitis B or C virus chronic active hepatitis. Serum samples for 2'5'-oligoadenylate synthetase determination were collected in basal conditions and 8 h after the administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin. Compared to control value (mean +/- SE) (40.2 +/- 7.9 pg/dl) serum 2'5'-oligoadenylate synthetase concentration was significantly increased 1.5-fold after interferon-alpha (63.4 +/- 11, p < 0.001), 2.8-fold after indomethacin (115.5 +/- 21, p < 0.001) and 3.7-fold after interferon-alpha plus indomethacin (148.9 +/- 25.1, p < 0.001). When patients with different viral infections were considered separately, basal 2'5'-oligoadenylate synthetase concentrations were similar in both HBeAg- and HBeAb-positive patients, but about 2-fold higher in hepatitis C virus. Compared to the control value, interferon-alpha caused a 1.5-fold increase in HBeAg- and hepatitis C virus-positive and a 2-fold increase in HBeAb-positive patients. Indomethacin led to a 1.8-fold increase in HBeAg, a 2-fold increase in hepatitis C virus-positive and surprisingly a 6.8-fold increase in HBeAb-positive patients. Simultaneous administration of the two drugs had an additive effect on the 2'5'-oligoadenylate synthetase increase in HBeAg-positive (2.4-fold increase) and a synergistic effect in hepatitis C virus- and HBeAb-positive patients (2.7- and 10.2-fold increase, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indomethacin enhances serum 2'5'-oligoadenylate synthetase in patients with hepatitis B and C virus chronic active hepatitis. 769 63

To evaluate the relationship between the sugar chain structure and biological activity, fibroblast-derived glycosylated human interferon-beta, Chinese hamster ovary cell-derived glycosylated recombinant human interferon-beta and Escherichia coli-derived unglycosylated recombinant human interferon-beta were evaluated using human hepatoblastoma cells in vitro. Native fibroblast interferon-beta expressed more cell-growth inhibitory action, 2'5'-oligoadenylate synthetase induction, and the inhibition of hepatitis B virus DNA replication than its asialoform and two recombinant interferon-betas. These results showed that the sugar chain structure of human interferon-beta affects its biological activity on human hepatoblastoma cells.
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PMID:Carbohydrate-dependent biological activities of glycosylated human interferon-beta on human hepatoblastoma cells in vitro. 778 83

Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000 U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300,000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects. 830 Oct 59


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