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)

Nineteen patients with chronic non-A, non-B hepatitis (CH-NANB) and 24 patients with chronic hepatitis B (CH-B) were treated with interferons, and the therapeutic and biological responses of the two groups (CH-NANB and CH-B) were compared. All patients had had sustained elevations in serum glutamic pyruvic transaminase (sGPT) levels for more than 6 months and were proven to have chronic hepatitis by liver biopsy. alpha-Interferon (IFN-alpha) or beta-interferon (IFN-beta) was administered in low doses of 3 to 6 mega international units (MIU) daily for 4 wk. Liver biopsies were taken from 13 CH-NANB and 14 CH-B subjects just before and immediately after treatment, and histological findings were assessed by the histology activity index (HAI) score. SGPT levels decreased much more rapidly and markedly in CH-NANB than in CH-B during IFN therapy (p less than 0.01). The HAI score decreased 3.5 points in CH-NANB and 1.0 point in CH-B between pretreatment and posttreatment. Serum beta 2-microglobulin (beta 2-MG) increased in both types of chronic hepatitis during treatment, but the rate of elevation was significantly less in CH-NANB than in CH-B (p less than 0.001). beta 2-MG expression on hepatocytes stained by the PAP method was almost identical in CH-NANB before and after treatment, whereas it increased steadily in CH-B. The serum 2',5'-oligoadenylate synthetase level increased in both types of hepatitis on IFN administration. These results suggest that, in IFN treatment for CH-NANB, the antiviral actions of IFNs may play a very important role in reducing the activity of chronic hepatitis.
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PMID:Comparative study of clinical, histological, and immunological responses to interferon therapy in type non-A, non-B, and type B chronic hepatitis. 168 84

The efficacy of interferon therapy (IFN) was investigated in 46 patients with chronic non-A, non-B (NANB) hepatitis, of would 40 (87.0%) were positive for anti-HCV antibody (Ab) (C-100-3). Three kinds of IFN were used; human lymphoblastoid interferon (HLBI), interferon alpha-2b and interferon beta. Total doses of IFN ranged from 1 million units (MU) to 10 MU and treatment duration ranged from 2 weeks to 144 weeks. Of 46 patients 34 (73.9%) responded to IFN. Nine patients have maintained normal ALT levels and 5 patients have maintained near-normal ALT levels for more than 6 months after cessation of IFN treatment. In these cases the titers of anti-HCV Ab had decreased significantly at the end of IFN therapy and 6 months after IFN therapy respectively. The mean age was young and the mean disease duration was short in effective cases. As for doses and treatment duration of IFN, low doses of IFN requires long treatment duration to acquire continuous efficacy and high doses of IFN requires rather short treatment durations. Therefore, early IFN treatment, higher doses and longer periods of IFN treatment may improve the response rate of patients with chronic NANB hepatitis.
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PMID:Treatment of chronic non-A, non-B hepatitis with interferon. 190 72

Effects of various cytokines on the proliferation of mouse hepatocytes were investigated. Human recombinant IL-6 not only enhanced the proliferation of mouse hepatocytes in the presence of epidermal growth factor, but also without epidermal growth factor. However, other human or mouse cytokines such as recombinant IL-1, IL-2, IL-3, IL-4, IFN-beta and IFN-gamma, which are known to regulate immune responses and/or hematopoiesis, had no effect on the proliferation of hepatocytes. These results suggest that IL-6 plays a crucial role in regulating the regeneration of hepatocytes after hepatitis or partial hepatectomy.
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PMID:Effect of human recombinant interleukin-6 on the proliferation of mouse hepatocytes in the primary culture. 218 3

To characterize receptors for alpha interferon (IFN-alpha) on human cells, we studied the binding of radioiodinated recombinant DNA-derived human IFN-alpha to human peripheral blood mononuclear cells (PBMCs) from normal individuals and from patients with chronic type B hepatitis. At 1 degree C, binding reached equilibrium after 2 to 3 hours of incubation, and saturation of specific binding occurred at a concentration of approximately 4000 fmol/ml. Binding of labeled IFN-alpha was specific; it was inhibited by an excess of unlabeled IFN-alpha or IFN-beta but not by cholera toxin or IFN-gamma. Scatchard analysis of binding data yielded for normal PBMCs an apparent dissociation constant (Kd) of 1.54 +/- 0.49 x 10(-9) mol/L (mean +/- SD) and an apparent maximum binding capacity (Bmax) of 7.35 +/- 1.22 x 10(-11) mol/L. Corresponding values for patients with chronic type B hepatitis who had not received treatment were similar, suggesting that such patients should respond normally to endogenous interferon. Analysis of data on the binding of labeled IFN-alpha to normal PBMCs from experiments in which a high specific activity ligand or subpopulations of PBMCs had been used revealed that receptors for IFN-alpha on PBMCs are heterogenous. In patients with chronic type B hepatitis who were receiving IFN-alpha therapy, the apparent Kd was increased (3.02 +/- 0.91 x 10(-9) mol/L) without any appreciable change in the apparent Bmax or any appreciable changes in the proportions of subpopulations of PBMCs. This decreased affinity induced by IFN-alpha treatment does not necessarily reflect an effect on a single binding site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific binding of human alpha interferon to high-affinity cell-surface binding sites on peripheral blood mononuclear cells. 252 45

Recombinant murine interferon beta (rMuIFN-beta) protected susceptible C57BL/6 mice against lethal mouse hepatitis virus (MHV) infection. rMuIFN-beta was life saving if it was given intraperitoneally beginning 21 h before infection and daily thereafter for 9 days, and lengthened the survival time if given from 3 h after infection. rMuIFN-beta treatment beginning 24 h after infection was ineffective. The survival rate was dose-dependent, and the 50% effective dose of rMuIFN-beta for survival was 1780 IU per day. rMuIFN-beta pretreatment inhibited virus growth completely in the brain and moderately in the liver and spleen and prevented severe hepatic lesions. rMuIFN-beta also protected beige mice and cyclophosphamide-treated mice against MHV infection, suggesting that activation of natural killer cells or T-cells by rMuIFN-beta is not critical for protection.
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PMID:Protective effect of recombinant murine interferon beta against mouse hepatitis virus infection. 283 Aug 46

Interferon-gamma (IFN-gamma) was induced from a human peripheral mononuclear fraction by incubation with a streptococcal preparation stabilized with penicillin G (OK432). This IFN-gamma-producing activity was significantly reduced in patients with chronic hepatitis and hepatocellular carcinoma. In patients with liver cirrhosis it was also reduced but not significantly. Serum hepatitis B virus DNA and skin tests for the purified protein derivative of tuberculin, phytohemagglutinin-P and a polysaccharide fraction prepared from streptococcus pyogenes Su strain were determined to have no significant relation to this IFN-gamma-producing activity. Although the addition of interleukin 2 (IL-2) to the culture medium enhanced the IFN-gamma-producing activity, there was no difference in this enhancement between normal control and chronic hepatitis. Therefore reduction of the IFN-gamma-producing activity observed in chronic hepatitis seems to be caused by a decreased number of IFN-gamma-producing activity cells or hypofunction of these cells or both. Since HBeAg became negative in patients whose IFN-gamma-producing activity was increased by the administration of the immunopotentiator OK432 or IFN-beta, the IFN-producing system in the patients with B type hepatitis may contribute to the elimination of HBV. Adenine arabinoside suppressed IFN-gamma-producing activity both in vivo and in vitro.
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PMID:In vitro interferon producing activity of peripheral mononuclear cells in patients with chronic liver disease. 303 38

Human recombinant interleukin 2 (hrIL-2) was demonstrated in vitro to be chemotactic for mouse large granular lymphocytes (LGL) activated in vivo by virus infection. Peritoneal exudate cells harvested from virus-infected mice were used as a source of LGL. LGL collected from mouse hepatitis virus-infected mice at 3 days postinfection were a source for NK 1.1 positive natural killer (NK)/LGL. LGL collected from mice treated with antiserum to gangliotetraosylceramide and infected with lymphocytic choriomeningitis virus for 7 days were used as a source for Lyt-2 positive cytotoxic T lymphocytes (CTL)/LGL. Both NK/LGL and CTL/LGL responded chemotactically to hrIL-2, purified IFN-beta, and to crude cell-free washout fluids collected from the peritoneal cavity of virus-infected mice. hrIL-2 had chemotactic activity for virus-elicited granular and agranular lymphocytes but did not attract the contaminating macrophages, in contrast to IFN-beta, which displayed chemotactic activity for virus-elicited granular and agranular lymphocytes as well as macrophages. The migration to hrIL-2 was inhibited by a monoclonal antibody (7D4) to the IL-2 receptor, but treatment with 7D4 did not affect migration in response to IFN-beta. Microscopic examination of Wright's-Giemsa-stained migrated NK/LGL and CTL/LGL revealed that the majority of migrated LGL in either LGL population had a blast cell morphology (enlarged cells with rich basophilic cytoplasm). The frequency of cells bearing the LGL morphology within the virus-elicited nonadherent peritoneal exudate cell population was on incubation in vitro, stabilized by either hrIL-2 or IFN-beta. These data suggest that another important immunomodulating function of IL-2 may be to attract activated NK/LGL and CTL/LGL to sites of inflammation.
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PMID:Chemotactic effect of human recombinant interleukin 2 on mouse activated large granular lymphocytes. 349 69

Peritoneal macrophages were used to analyse host genetic control of mouse hepatitis virus type 4 (MHV-4) infection. Both infectious centre and immunofluorescence assays indicated that only a subset of macrophages from either susceptible (BALB, C3H or C57BL/6J) or resistant (SJL/J) mice were initially infected with MHV-4 during the first cycle of infection. However, compared to macrophages from susceptible mice, three- to sixfold fewer SJL/J macrophages were infected, and there was no amplification of virus replication by involvement of adjacent cells during the second cycle of infection. Treatment of macrophages from susceptible mice with interferon beta could not duplicate the aborted second cycle of infection that occurred in macrophages from resistant mice.
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PMID:Host genetic control of mouse hepatitis virus type 4 (JHM strain) replication. I. Restriction of virus amplification and spread in macrophages from resistant mice. 608 81

The interferon (IFN) system consists of both the formation of the various IFN proteins, and the diverse cellular responses which these induce: these result from the intracellular changes which follow their binding to a specific cell surface receptor. There is only a single human gamma, omega and beta IFN; in contrast, there are 13 closely related chemical species ("subtypes") of human alpha IFN, which are nevertheless chemically and biologically distinct. IFN preparations made from mass cultured human cells or by using recombinant DNA techniques are now readily available for clinical use. IFN have a major role in the defence of the body against virus infections. In acute virus infections, preformed exogenous IFN cannot be given soon enough to be of value. However, IFN-alpha and IFN-beta have proved of considerable value in some chronic virus infections, particularly chronic virus hepatitis and chronic papillomavirus infections. The doses routinely used are associated with both acute and chronic toxic side effects. Also, some patients form specific neutralising antibodies against the particular IFN preparation injected, which may abrogate all the benefits of the treatment. Nevertheless, IFN are now established as agents for use in routine medical practice.
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PMID:Cytokines in the treatment of virus infections. 786 46

The hepatitis delta virus (HDV) genome consists of circular ssRNA which has extensive intramolecular complementarity and can form a dsRNA rod-like structure. If such RNA species were to exist in an unmasked form in cells, they would be expected to induce interferon (IFN) expression and activate two IFN-inducible dsRNA-dependent enzymes with anti-viral activity, namely the dsRNA-dependent protein kinase (PKR) and 2',5' oligoadenylate (2',5' A) synthetase. Since the virus replicates to high copy number for prolonged periods in infected cells it is apparently able to evade these antiviral mechanisms. The RNA genome may be masked and fail to induce or activate the antiviral response, or the virus may inhibit such a response. Treatment of a hepatoma cell line, Huh7, and a fibrosarcoma cell line, HT1080, stably transfected with a trimeric HDV cDNA construct, with IFN-alpha or IFN-gamma for up to seven days failed to influence the level of expression of genomic or antigenomic HDV RNA, or delta antigen (Ag). This is consistent with either failure of activation or inhibition of the IFN response. However the induction of several IFN-responsive genes, including PKR, 2',5' A synthetase and class I MHC is normal and cotransfection of a construct expressing delta Ag did not affect expression from an IFN-inducible chloramphenicol acetyltransferase construct. In addition, the activation of PKR is not inhibited in HDV-expressing cells and antiviral assays suggest that the ability of these cells to mount an antiviral response to at least two cytopathic viruses is unaffected. IFN-beta is inducible normally by dsRNA in cells transfected with the delta cDNA trimer. We conclude that HDV replication is not inhibited by IFN-alpha or IFN-gamma, even though the responses of cells expressing HDV RNA and antigen to IFN and dsRNA are intact.
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PMID:Hepatitis delta virus replication in vitro is not affected by interferon-alpha or -gamma despite intact cellular responses to interferon and dsRNA. 791 7


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