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)

The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg.
 ...
PMID:Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor-alpha on hepatitis B virus enhancer activity. 131 44

Interferon-alpha (IFN-alpha) is known to inhibit both DNA and RNA viruses, including hepatitis B virus (HBV). In humans the antiviral effect, if any, of IFN-alpha on hepatitis delta virus (HDV) is complicated by the fact that HDV is spread only to patients already infected with HBV. An in vitro model system was used to assay for an antiviral effect of IFN-alpha on HDV genome replication. Hep G2 cells were transfected with a plasmid containing a trimer of HDV and treated with IFN (20 or 100 units/mL) starting 1-7 days after transfection. RNA extracted from treated and nontreated cells was assayed by both slot blot and Northern analyses. The IFN-alpha treatment as expected increased the 2'-5' oligo A synthetase RNA activity, but it did not affect HDV genome replication. Thus, in the absence of HBV, it appears that HDV is resistant to IFN-alpha.
 ...
PMID:Resistance of hepatitis delta virus replication to interferon-alpha treatment in transfected human cells. 132 4

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Fundamental studies of hepatitis C virus: a review]. 133 74

Human hepatocyte expression of intercellular adhesion molecule-1 (ICAM-1) (CD54) was studied in vitro by exposing the well differentiated human hepatoblastoma cell line HepG2 to various cytokines. In addition, hepatitis B virus (HBV)-DNA transfected HepG2 cells were also analysed. Expression of ICAM-1 on HepG2 cells was then revealed with an immunohistochemical procedure. Untreated HepG2 cells were unreactive, but showed strong cytoplasmic ICAM-1 immunoreactivity after treatment with interferon-gamma (IFN-gamma). This induction was completely inhibited by addition of a neutralizing antibody directed to IFN-gamma. IL-1, IL-6, tumour necrosis factor-alpha (TNF-alpha) and IFN-alpha, used alone or in combination, did not induce ICAM-1 expression, neither did they inhibit the IFN-gamma-induced expression of this adhesion molecule on HepG2 cells. Untreated hepatitis B virus-DNA transfected HepG2 cells expressed membranous ICAM-1. These results indicate that IFN-gamma is the main cytokine trigger for ICAM-1 expression on HepG2 cells, suggesting that in areas of liver inflammation this adhesion molecule is up-regulated on hepatocytes by locally released IFN-gamma. In addition, expression of ICAM-1 by hepatitis B virus-DNA transfected HepG2 cells suggests other, still unknown, triggering mechanisms in the induction of such adhesion molecules, for instance gene activation by viral genome, or autocrine virus-induced hepatocellular cytokine production.
 ...
PMID:Induction of intercellular adhesion molecule-1 (CD54) on human hepatoma cell line HepG2: influence of cytokines and hepatitis B virus-DNA transfection. 134 74

A 28 year old woman with hepatitis B (HB) related chronic active hepatitis was treated with a 12 week course of alpha-interferon (alpha-IFN). She developed acute mono-arthritis 1 week after completion of treatment. Her rheumatoid factor (RF) was positive before alpha-IFN and fell steadily during therapy. This was followed by a rebound of RF level with the associated arthritis occurring 1 week after completion of the course of alpha-IFN. In absence of any medication RF gradually fell and became negative at the end of 1 year. This observation is thought to be related to the immunomodulatory effect of alpha-IFN either directly on RF production or indirectly through the control of hepatitis.
 ...
PMID:Mono-arthritis in a chronic hepatitis B patient after alpha-interferon treatment. 151 71

Constructs expressing the core, surface, X, or polymerase proteins of hepatitis B virus were transfected into human cells. In transient assays, only the polymerase inhibited the responses to interferons alpha and gamma (IFN-alpha and -gamma). Stable expression of the polymerase was achieved in the cell line 2fTGH, which carries an IFN-inducible marker gene, by growth under conditions that select for inhibition of the response to IFN-alpha, but the clones grew poorly. When expressed alone, the terminal protein domain of the polymerase gene inhibited the response to IFN-alpha and the reverse transcriptase plus RNase H domains appeared to be toxic. Clones of cells expressing terminal protein alone, selected for the loss of response to IFN-alpha, grew normally and had no detectable response to IFN-alpha, IFN-gamma, or double-stranded RNA. Binding of IFN-alpha to these cells was not impaired but did not lead to activation of the E alpha subunit of the IFN-induced transcription factor E. These observations are of potential importance in relation to the pathogenesis of chronic hepatitis B virus infection and the resistance of such infection to IFN-alpha therapy.
 ...
PMID:Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA. 170 74

Interferon has profound anti-viral, anti-proliferative and immunomodulatory effects. Future studies should be directed at observing how the immunomodulatory effects predict a response in certain groups of patients. Interferon is very useful in chronic hepatitis B but may require the addition of a steroid pulse. Individuals with low serum ALT appear to benefit most from a steroid pulse. Therapy should be given with a great deal of caution in patients with decompensated liver disease, as one may precipitate the untimely demise of the patient even though viral replication is decreased. One of the patients in the IFN study in fact did have decompensation after prednisone therapy, which subsequently led, a couple of months later, to a variceal haemorrhage. In summary, in treating hepatitis B viral infection, no single agent is totally effective and perhaps the combination of suppressing viral replication and augmenting the immune system is the optimal way to eradicate the virus. At present, an adequate response is found in only about 30-40% of patients even with 'optimal' therapy.
 ...
PMID:Alpha-interferon combined with immunomodulation in the treatment of chronic hepatitis B. 175 97

To examine whether sizofiran (SPG), a polysaccharide isolated from Schizophyllum commune Fries, could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV) nucleocapsid antigens, we investigated in vitro the production of interferon-gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe), and proliferation by peripheral blood mononuclear cells (PBMC) from six patients with chronic hepatitis B and four control individuals in the presence of recombinant HBcAg and purified HBeAg. Sizofiran alone in culture and in combination with HBV Ag was found to enhance IFN-gamma production and the proliferative response of PBMC from the patients compared with corresponding medium or HBV Ag alone culture. In contrast, antibody production was not elicited by SPG alone, but amplified by the drug in HBcAg-stimulated culture. In vitro leukocyte IFN-alpha addition increased IFN-gamma production, but suppressed the proliferation of PBMC from both controls and patients in the presence or absence of SPG and HBV Ag. These results indicate that SPG is able to modulate both cellular and humoral immune responses specific for nucleocapsid antigens in patients with chronic hepatitis B.
 ...
PMID:Effect of sizofiran, a polysaccharide, on interferon gamma, antibody production and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B. 176 62

The Bombyx mori nuclear polyhedrosis virus (BmNPV) in the silkworm was used successfully for mass production of biologically active foreign genes under the control of the polyhedrin promoter. This system was adapted for the production of large amounts of hepatitis B virus surface antigens (HBsAg). The DNA fragments coded for the middle protein, which is composed of the S protein with the pre-S2 region, were cloned, the signal protein gene of beta-IFN was added, and both were inserted into a cloning vector. After co-transfection with wild-type BmNPV, stable recombinant viruses were isolated by the limiting dilution method. Infected silkworm larvae with the recombinants expressed HBsAg at high levels (400-600 micrograms/ml). These products, consisting of two polypeptides with molecular weights of approximately 25,000 (p25) and glycosylated P25 (GP28), were purified as assembled 22-nm particles. We demonstrated that HBsAg from silkworms consists of S protein with 7 amino acids of Pre-S2.
 ...
PMID:High-level expression and characterization of hepatitis B virus surface antigen in silkworm using a baculovirus vector. 181 52

Chronic delta hepatitis is a severe disease with a rapidly progressive course for which currently no effective treatment exists. Treatment with alpha-interferon (alpha-IFN) can inhibit HDV replication and improve serum chemistries in a number of patients. Meta-analysis of five randomized controlled trials using at least 5 MU/m2 of alpha-IFN t.i.w. for a minimum of 3 months showed that alpha-IFN had a statistically significant effect in normalizing ALT values during therapy at a p level of less than 0.001, with a 10.24 odds ratio and a 28.69% risk difference (Mantel-Haentzel-Peto chi 2 = 24.13) but had no significant effect on ALT activity after its discontinuation. From hitherto available results, it appears that the best treatment schedule is a 5 MU standard dose of alpha-IFN given daily (QD) or 9 MU t.i.w. for at least 1 year, which is associated with a remission of the disease in 50-70% of patients. A trial conducted in Greece showed that the mean duration of disease remission under alpha-IFN therapy was 3.8 months per year compared to 1.7 months per year of non-treatment (relative risk = 2.8). Unlike hepatitis B, no factors predictive of the response to alpha-IFN therapy have been identified except, perhaps, for the duration of the disease. No adjuvants have been found to enhance the efficacy of alpha-IFN treatment and no therapeutic alternatives are available at present. Advances in understanding HDV replication and the pathogenetic mechanisms in chronic delta hepatitis may bring about significant improvement in its therapy in the future.
 ...
PMID:Use of alpha-interferon in the treatment of chronic delta hepatitis. 183 31


1 2 3 4 5 6 7 8 9 10 Next >>