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)

A previous study shows that Hsp60 not only interacts with, but also activates human hepatitis B virus polymerase, HBV Pol (S. G. Park and G. Jung, 2001, J. Virol. 75, 6962-6968). To provide a more detailed analysis of the relationship between the two proteins, (i) the binding sites on human HBV Pol for Hsp60 and (ii) the effect of pregenomic RNA on human HBV Pol-Hsp60 binding were analyzed. The binding sites on human HBV Pol were mapped with several deletion mutant proteins of the Pol expressed in insect cells by using recombinant baculovirus. Immunoprecipitation of each deletion mutant protein by M2 beads showed that binding of Hsp60 to human HBV Pol requires two minimal sites on human HBV Pol: amino acids 1 to 199 (TP) and amino acids 680 to 842 (RH). Human HBV Pol was also shown to bind to Hsp60 in HepG2 cells, the host cell line for human HBV. In addition, Hsp60 binding to the Pol was found to be dispensable to pregenomic RNA binding to human HBV Pol. Overall, this article infers that Hsp60 activates human HBV Pol through binding at the TP and RH domains of the Pol and the Pol binding to Hsp60 does not require pregenomic RNA.
 ...
PMID:Binding site analysis of human HBV pol for molecular chaperonin, hsp60. 1209 79

Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus (HBV) replication in vitro and in vivo that is currently in clinical trials for the treatment of chronic HBV infections. A major limitation of the current HBV antiviral therapy, lamivudine (3TC), is the emergence of drug-resistant HBV in a majority of treated patients due to specific mutations in the nucleotide binding site of HBV DNA polymerase (HBV Pol). To determine the effects of 3TC resistance mutations on inhibition by ETV triphosphate (ETV-TP), a series of in vitro studies were performed. The inhibition of wild-type and 3TC-resistant HBV Pol by ETV-TP was measured using recombinant HBV nucleocapsids, and compared to that of 3TC-TP. These enzyme inhibition studies demonstrated that ETV-TP is a highly potent inhibitor of wild-type HBV Pol and is 100- to 300-fold more potent than 3TC-TP against 3TC-resistant HBV Pol. Cell culture assays were used to gauge the potential for antiviral cross-resistance of 3TC-resistant mutants to ETV. Results demonstrated that ETV inhibited the replication of 3TC-resistant HBV, but 20- to 30-fold higher concentrations were required. To gain further perspective regarding the potential therapeutic use of ETV, its phosphorylation was examined in hepatoma cells treated with extracellular concentrations representative of drug levels in plasma in ETV-treated patients. At these concentrations, intracellular ETV-TP accumulated to levels expected to inhibit the enzyme activity of both wild-type and 3TC-resistant HBV Pol. These findings are predictive of potent antiviral activity of ETV against both wild-type and 3TC-resistant HBV.
 ...
PMID:Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. 1212 28

The presence of Deleted Genomes has been shown in a number of viral models including Hepadnaviridae. The analysis of woodchuck hepatitis B virus (WHV) population after experimental infection of woodchuck 197 (W197) with WHV7-PI inoculum revealed the presence of two Deleted Genomes: DG600 lacking a 1330 bp region (Core/Polymerase/PreS1) and DG900 showing a deletion of 869 nts (Pol/PreS/S). These mutants were also present in WHV7-PI. The successive WHV experimental infections in adult animals were performed using W197-w7 inoculum containing DG600 and DG900. Infections were divided into three groups presenting different patterns of viral replication, different presence of markers, occurrence of variants and persistence of infection. The first group displayed 2-3 weeks viremic phase and WHV-DNA titres of 10-30 ng/ml; the second a longer viremic phase (8-9 weeks) and higher WHV-DNA titres (up to 78 ng/ml). In contrast, the third group exhibited lifetime presence of WHV-DNA and WHVeAg in serum and viral replication in liver. The Deleted Genomes were transmitted in the newly infected animals with the same genomic organization. DG600 was persistently found only in chronically infected woodchuck, whereas a different pattern of presence was described for DG900. The characterization of these classes of deleted mutants in woodchuck-WHV model raises new questions on the link between DGs and persistent infections.
 ...
PMID:In vivo transmission and dynamics of deleted genomes after experimental infection of woodchuck hepatitis B virus in adult animals. 1241 78

Hepatitis B virus still remains the main etiological factor of acute hepatitis in Poland. The review presents the immunogenicity of the vaccine and indications for immunizing patients with chronic liver disease against hepatitis B. Recommended vaccine dosages and schedules are presented.
Pol Merkur Lekarski 2002 Aug
PMID:[Immunizations against viral hepatitis B in patients with chronic liver disease]. 1242 Mar 35

Hepatitis B virus infection remains a major epidemiological health problem worldwide, due to the high prevalence (350 mln new cases per year) and clinical consequences of this infection including chronic hepatitis, liver cirrhosis and primary liver cancer. Two cases of patients with clinical symptoms of chronic hepatitis B without traditional serological markers, pointing to active hepatitis B viral replication, were presented. The diagnosis has been confirmed by molecular methods, typical histopathology of liver biopsy specimens, and biochemical improvement after lamivudine treatment.
Pol Merkur Lekarski 2002 Dec
PMID:[Possibility of persistent replication of HBV in patients with serological evidence of virus elimination]. 1266 53

Woolly monkey hepatitis B virus (WMHBV) is a new member of Hepadnaviridae that was isolated from a New World monkey and is phylogenetically distinct from the HBV family. In this study, we explored the functional significance of sequence divergence in the HBV and WMHBV genomes. Independently expressed TP and RT domains of the WMHBV reverse transcriptase (Pol) formed a complex functional for in vitro nucleotide priming, consistent with previous results from priming reactions conducted with HBV. Transcomplementation assays between HBV and WMHBV TP and RT components for in vitro priming demonstrated functional compatibility, although priming with the combination of WMHBV RT and HBV TP was reduced. Examination of cross-species protein-protein interactions revealed that WMHBV core coprecipitated with HBV TP and RT, as well as with WMHBV TP and RT. Analysis in Huh7 cells revealed that WMHBV core and Pol complemented core-negative and Pol-negative HBV mutant genomes for replication. These results highlight the conservation of function despite significant sequence divergence in these viruses.
 ...
PMID:Transcomplementation of core and polymerase functions of the woolly monkey and human hepatitis B viruses. 1270 82

Programmes of vaccination against hepatitis B were introduced in Poland for the first time in 1989. The paper presents the influence of these programmes on the decrease of hepatitis B incidence in the last twelve years. We have described the methods of estimating the efficacy of hepatitis B vaccination and presented the causes of weak anti-HBV response depending on the vaccine that was used and the features of the population that was vaccinated. Special vaccination schemes were established to achieve optimal response in chronically ill or immunosuppressed patients. We have cited the latest opinions concerning booster doses in healthy people and in patients at high risk of HBV infection.
Pol Merkur Lekarski 2003 Apr
PMID:[Vaccination against hepatitis B in Poland: importance, effectiveness and future prospects]. 1286 2

Fibrosis is the process accompanying majority of chronic diseases of liver, independent of etiological factor and leading to cirrhosis and hepatic failure. Monitoring fibrosis process by liver's biopsy is limited, so many attempts are undertaken to assess concentrations of definite proteins in blood, which could be easily accessible marker of intrahepatic process. It seems, that among others, determinations of blood concentration of aminoterminal propeptide of procollagen III--index of collagen's III synthesis and TGF-beta 1--cytokine of antiproliferative action and inhibiting hepatocytes' growth, yet inducing fibroblasts' growth and stimulating fibrosis process brings out such a possibility. The aim of the study was simultaneous determination of TGF-beta 1 and PIIINP concentration in blood of patients with chronic hepatitis B and C before interferone's therapy in comparison to healthy controls, assessment of the parameters in dependence on stage of liver fibrosis and determination of correlation between TGF-beta 1 and PIIINP. Studies were performed in 40 patients with chronic hepatitis B (CAH B) and 35 patients with chronic hepatitis C (CAH C). Significantly increased serum concentrations of TGF-beta 1 as PIIINP in both groups of patients (CAH B and CAH C; grading 2-3, staging 1-2) in comparison with control group was noted. Significant positive correlation of TGF-beta 1 and PIIINP serum concentrations in both groups of patients was observed. There was not significant changes in PIIINP serum levels in patients with hepatitis B and C in dependence on stage of liver fibrosis (staging 1 vs staging 2) but TGF-beta 1 serum levels was significantly increased in CAH B and C patients with higher stage of liver fibrosis process. On the base of obtained results, it seems that changes in TGF-beta 1 concentrations in blood reflect "grading" and "staging" and can be a marker of intensification of intrahepatic fibrosis process whereas PIIINP levels in blood have rather the relation with "grading".
Pol Arch Med Wewn 2003 Jun
PMID:[Serum aminoterminal peptide of type III procollagen (PIIINP) and transforming growth factor-beta1 (TGF-beta1) levels in patients with chronic hepatitis B and C]. 1456 92

The detection and quantification of hepatitis B virus (HBV) genomes appear to be the most reliable method for monitoring HBV infection and assessing responses to antiviral treatment. For quantitative determination of HBV viremia molecular biology-based assays are used. The aim of this study was to compare and evaluate the performance of two HBV DNA detection and quantification commercial assays: hybrid-capture Digene Hybrid Capture HBV DNA assays and based on competitive polymerase chain reaction (PCR) Cobas Amplicor HBV Monitor Roche Diagnostics. Reproducibility, linearity, sensitivity were determined with 2-fold dilution series of high-titers samples and with 113 sera samples from patients with chronic HBV infection. Within-run and between-run coefficients of variation ranged from 2.4-9.7% for hybrid-capture and from 3.7-15% for PCR-based Monitor. The hybrid-capture and PCR Monitor assays appeared to be linear throughout their range of quantification: 5-2000 pg/ml and 2 x 10(2)-2 x 10(5) copies/ml respectively. The HBV DNA units used in the two assays were not comparable. Hybrid-capture and Monitor gave concordant results with 87 (82.1%) of 106 samples. The assays were both positive with 79 (74.5%) samples and were negative in 7 (7.5%) cases. Hybrid-capture and Monitor gave discordant results in 17 (17.9%) cases. The Monitor Assay was positive in 13 (61.9%) of the 21 samples negative in hybrid-capture. The competitive PCR-based Monitor assay appear to be significantly more sensitive but slightly less reproducible than the hybrid-capture. In the group of patients with seroconversion to anti-HBe PCR method should be used for measurement of viral load. In the presence of HBe antigen concentration of HBV DNA may be tested by hybrid-capture assay. Also these two assays may be used in complementary fashion in the management of HBV infected patients. It seems reasonable to use a hybrid-capture assay first, because its linear range of quantification is extended to high values and to use Monitor for samples that are negative in hybrid capture, because, its significantly higher sensitivity. However the lack of standardization among the assays makes it difficult to compare the results.
Pol Arch Med Wewn 2003 Dec
PMID:[Comparison of two commercial molecular assays for quantitative measurement of hepatitis B viral DNA]. 1505 39

Current therapy of chronic hepatitis B with interferon-a or lamivudine is directed first of all to reduce viral replication. Unfortunately these relatively expensive therapeutic methods can eliminate the infection in only one third of patients. However the pathogenesis of chronic infection with hepatitis B virus is related mostly to the deficits of specific immune response both cellular and humoral. Therefore research on therapeutic vaccination have been started recently. It was supported by development in the last years vaccines, that applied prophylactically demonstrated extraordinary immunogenicity and efficiency. Short story on research related to use of this low cost method for the fight against one of the most common infectious disease was presented in this paper. Experimental studies and small number of clinical trials with recombinant and lipopeptide vaccines, and the most recent based on viral DNA, demonstrated their safety and simultaneously enriched knowledge on the disease pathogenesis. This therapy did not lead to elimination of the infection in the proportion greater than interferon-a or lamivudine, but enables to faster reduction of its activity. Clinical trials including combined use of current therapeutical standards and vaccine immunotherapy, can be expected in coming years.
Pol Merkur Lekarski 2003 Dec
PMID:[Therapeutic vaccination in chronic hepatitis B: chance or utopia?]. 1505 47


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