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

All etiologies of acute viral hepatitis are associated with a transient suppression of hemopoiesis and, rarely, with the development of aplastic anemia. Both hepatitis A and hepatitis B viruses directly inhibit the growth and differentiation of human bone marrow progenitor cells in vitro. We now report a similar effect of a non-A, non-B (NANB) hepatitis agent on human bone marrow progenitor cells. Three chimpanzees were inoculated with a putative NANB agent. Coded sera were blindly evaluated for their ability to affect human bone marrow colony formation in vitro. Sera obtained during the acute phase of NANB hepatitis inhibited the in vitro growth of human erythroid (CFU-E, BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells, compared with sera obtained before inoculation. Sera obtained after remission of both the biochemical and histological hepatitis and sera obtained from a chimpanzee who underwent biochemical but not histological remission did not inhibit the stem cell assays as much as the acute phase sera. These results suggest an approach to identifying the viremic phase of NANB hepatitis. Inhibition of human bone marrow proliferation appears to be a common property of all known hepatitis viruses.
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PMID:Inhibition of human hemopoiesis by non-A, non-B hepatitis virus. 249 12

Cytokines, mediators of intercellular communication, penetrate as a new therapeutic group in to haematology, oncology, immunology and other disciplines. Recently two main spheres of indication of wider clinical use are in the foreground: 1. treatment of leukaemias and advanced solid tumours (interferons, interleukin-2, tumour-necrosis factor and others) and 2. treatment of impaired haematopoiesis (in clinical practice in particular erythropoietin, granulocyte-macrophage and granulocyte colonies stimulating factor). Other possibilities are offered by cytokines in the treatment of viral diseases (in addition to hepatitis B and C, perspectively also AIDS), inborn immunodeficiencies, progressive systemic sclerosis and other indications. In particular in oncological diseases, contrary to original assumptions, monotherapy with cytokines will not be greatly extended and a combination of cytokines with classical treatment will be used. The limiting factor in addition to cost is the considerable toxicity of some cytokines which calls for alternative routes of administration (local, compartmental etc).
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PMID:[Cytokine therapy]. 771 24

4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA) is the most antivirally active member of a novel class of optically active isomeric dideoxynucleosides in which the base has been transposed from the natural 1' position to the 2' position and the absolute configuration is (S,S). IsoddA was active against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2 (strain ZY), and HIV-1 clinical isolates. Combinations of the compound with zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or 5-fluoro-2'-deoxy-3'-thiacytidine showed synergistic inhibition of HIV. A moderate reduction of activity was observed with clinical isolates resistant to zidovudine. An IsoddA-resistant virus (eightfold-increased 50% inhibitory concentration) was selected in vitro by repeated passage of HIV-1 (HXB2) in the presence of increasing concentrations of IsoddA. The reverse transcriptase-coding region of the mutant virus contained a single base change resulting in a change at codon 184 from Met to Val. IsoddA was also active against hepatitis B virus (HBV) in vitro; however, it lacked substantial selective activity in an in vivo HBV model. IsoddA was inefficiently phosphorylated in CEM cells; however, the half-life of the triphosphate was 9.4 h, and IsoddATP was a potent inhibitor of HIV-1 reverse transcriptase, with a Ki of 16 nM. The cytotoxicity 50% inhibitory concentrations of IsoddA were greater than 100 microM for CEM, MOLT-4, IM9, and the HepG2-derived HBV-infected 2.2.15 (subclone P5A) cell lines but were 12 and 11 microM for human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol. 854 Jul 5

MxA protein is interferon inducible, and its role as an antiviral mediator is being studied in various viral diseases. Several cytokines, including type 1 interferons (alpha and beta), interleukins 2 and 12, and granulocyte, macrophage, and granulocyte-macrophage colony-stimulating factors, were tested for their ability to induce human MxA protein synthesis in peripheral blood mononuclear cells from 15 chronic hepatitis B virus-infected patients and 6 healthy subjects as controls. Constitutive MxA expression was scarce in patients and controls but increased significantly in response to type I interferons. MxA responsiveness to interferon alpha was diminished significantly in chronic hepatitis B patients, compared with healthy donors (P < 0.05); this effect was more marked in patients with high viremia levels. Interleukins 2 and 12, and none of the colony-stimulating factors tested, induced low, but detectable, MxA protein levels. These results indicate that chronic infection by hepatitis B virus may impair activation of the immune cells and their capacity to respond to type 1 interferons.
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PMID:Impaired interferon induction of human MxA protein in chronic hepatitis B virus infection. 909 49

In this study, we provide direct evidence that the magnitude and nature of the immune response to a DNA vaccine can be differentially regulated by codelivery of various mouse cytokine genes. Mice immunized with a hepatitis B virus (HBV) DNA vaccine and the IL-12 or IFN-gamma gene exhibited a significant enhancement of Th1 cells and increased production of anti-HBV surface IgG2a Ab, as well as a marked inhibition of Th2 cells and decreased production of IgG1 Ab. In contrast, coinjection of the IL-4 gene significantly enhanced the development of specific Th2 cells and increased production of IgG1 Ab, whereas Th1 differentiation and IgG2a production were suppressed. Coinjection of the IL-2 or the granulocyte-macrophage-CSF gene enhanced the development of Th1 cells, while the development of Th2 cells was not affected, and the production of IgG1 and IgG2a Ab were both increased. The CTL activity induced by HBV DNA vaccination was most significantly enhanced by codelivery of the IL-12 or IFN-gamma gene, followed by the IL-2 or granulocyte-macrophage-CSF gene, whereas codelivery of the IL-4 gene suppressed the activity. When challenged with HBV surface Ag (HBsAg)-expressing syngeneic tumors, significant reduction of tumor growth was observed in mice that were coadministered the IL-12 gene but not the IL-4 gene. Taken together, these results demonstrate that application of a cytokine gene in a DNA vaccine formulation can influence the differentiation of Th cells as well as the nature of an immune response and may thus provide a strategy to improve its prophylactic and therapeutic efficacy.
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PMID:Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. 957 May 50