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)

Immune complexes could be formed with hepatitis B Ag and anti-IgG serum after treatment of the antigen with detergent, CsCl or glycerol, but not before. It is suggested that an antigenic determinant specifically reacting with anti-IgG forms an integral part of hepatitis B Ag. This determinant is ordinarily obscured in the undamaged antigen.
 ...
PMID:Hepatitis B antigen: IgG components shown by immune electron microscopy. 5 92

Various physico-chemical parameters have been studied in order to improve the production of hepatitis B virus pre-S2 antigen (middle surface antigen) by the methylotrophic yeast Hansenula polymorpha. Antigen production was done in two steps: first, production of cells on glycerol (Phase 1), followed by induction of antigen expression with methanol (Phase 2). Dense cultures of H. polymorpha, equivalent to 35-40 g/l (dry weight), were readily obtained in small fermenters using minimal medium containing glycerol as carbon source. Antigen expression in this minimal medium, after induction with methanol, was however, low and never exceeded 1.6 mg/l of culture. Antigen production was greatly enhanced by adding complex organic nitrogen sources along with methanol at induction time; yeast extract was the best of all the sources tested. In shake flasks, antigen production was proportional to yeast extract concentration up to 7% (w/v) yeast extract, it became clear the the nutritional conditions for good antigen expression were different from those for good biomass production. The effects of yeast extract were reproduced in small fermenters: antigen levels reached 8-9 mg/l in medium containing 6% (w/v) yeast extract during induction with methanol. The mechanisms of yeast extract's effects are still unknown but are probably nutritional. The recombinant H. polymorpha strain produced both periplasmic and intracellular antigen. The periplasmic antigen was shown to be present as 20-22-nm particles and was therefore immunogenic. Immunoblotting indicated that part of the pre-S2 antigen was present as a 24-kDa degradation product. These studies have led to a 140-fold increase in volumetric productivity of antigen and to a 4.6-fold increase in specific production.
 ...
PMID:Fermentation study for the production of hepatitis B virus pre-S2 antigen by the methylotrophic yeast Hansenula polymorpha. 136 97

The hepatitis B virus particle consists of an envelope carrying the surface antigen of the virus and an internal capsid consisting of the core antigen (HBcAg). The internal capsid contains the circular, partially dsDNA genome and the viral polymerase. Empty core particles have been produced in Spodoptera frugiperda cells using a recombinant baculovirus vector, YM1KTc, that expresses a 21.4K derivative of the HBcAg gene. The particles have been purified to homogeneity by caesium chloride density gradient centrifugation followed by glycerol gradient centrifugation. Physicochemical analysis of the core particles showed that they exhibited a sedimentation coefficient (s20,(0)w) of 82.5S and a diffusion coefficient (D) of 1.28 x 10(-7) cm2/s. The Mr obtained by substitution of these values in the Svedberg equation was 5.8 x 10(6), using a partial specific volume of 0.73 ml/g for the viral protein as estimated from the amino acid composition. The Mr determined from sedimentation equilibrium analyses was 6.3 x 10(6). Spectrophotometric and metabolic labelling analyses failed to detect nucleic acids in the core preparations. The data are at variance with the prediction that cores exhibit a T = 3 symmetry and contain some 180 subunits. The results suggest that the baculovirus-expressed cores may contain up to 300 subunits of HBcAg protein.
 ...
PMID:Physicochemical analysis of the hepatitis B virus core antigen produced by a baculovirus expression vector. 225 55

Hepatitis B surface antigen (HBsAg, an exogenous protein) was produced by fermenting recombinant Saccharomyces cerevisiae containing the HBsAg gene. The relative HBsAg concentrations increased from 3.89 to 8.12 when glucose content was reduced and the culture medium was supplemented with glycerol and sucrose; specific activity also increased by a factor of 2.69. The temperature variation sequence for fermentation processes was established from experimental results. The amount of HBsAg gene expressed reached 13.51 in relative concentration terms. The stability of the recombinant plasmid containing the HBsAg gene was studied by the varying fermentation temperatures in a fed-batch process. There was a conversion activity distribution for the yeast containing the exogenous DNA, which affected HBsAg production by the genetically engineered yeast in fermentation processes.
 ...
PMID:Effects of culture medium composition and temperature on hepatitis B surface antigen expression by recombinant yeast in fermentation processes. 249 23

PreS1 region gene fragment encoding the N-terminal 56 amino acid (aa) of hepatitis B virus (HBV, adr subtype), which encodes B- and T-cell epitopes and an hepatocyte receptor binding site, was synthesized by PCR and fused to the 3'-end of MalE gene encoding maltose-binding protein (MBP) to yield expression plasmid pMalpreS1-56. The plasmid was introduced into Escherichia coli DH5 alpha and expressed at 37 degrees C under the control of inducible tac promoter. The resulting fusion protein was highly expressed in a soluble form, about 40% of total cellular proteins, but it bound only partially to an amylose column. Therefore, the soluble preS1 fusion protein was purified to near homogeneity by two passages of anion-exchange chromatography followed by gel filtration. The yield of the fusion protein was 70 mg per 1 culture that had been induced by IPTG for 6 h. The purified fusion protein was specifically cleaved by a Factor Xa digestion to release the preS1 peptide, which was then purified by gel filtration to homogeneity. The purity, integrity, antigenicity and immunogenicity of the purified preS1 peptide was confirmed by glycerol-SDS-PAGE, Western analysis, N-terminal amino acid sequencing and an indirect ELISA.
 ...
PMID:High level expression of hepatitis B virus preS1 peptide in Escherichia coli. 776 64

The ability of macromolecules to protect 8-cell mouse embryos during a vitrification protocol was assessed by the comparison of a synthetic macromolecule, polyvinylpyrrolidone (in the form of Percoll), and a biological macromolecule, human serum albumin (HSA). Vitrification solutions, which included glycerol (50% v/v), sucrose (0.75 mol/l) and either macromolecule Percoll (50% v/v) or HSA (1.125% w/v), were found to provide similar rates of survival. Both compounds resulted in a significant reduction in the incidence of disruption to the zonae pellucidae of cryopreserved embryos, to 4.8 +/- 1.3% and 10.3 +/- 1.2% respectively, when compared to the outcome when neither was present in the vitrification solution (20.4 +/- 2.5%; P < 0.01). Polyvinylpyrrolidone in the form of Percoll offers advantages over HSA in this work: it provides a lower rate of zona disruption and avoids the need for screening for pathogenic contaminants such as human immunodeficiency virus and hepatitis B and C.
 ...
PMID:Synthetic and biological macromolecules: protection of mouse embryos during cryopreservation by vitrification. 778 47

We recently found that phosphatidyl-2',3'-dideoxycytidine (phosphatidyl-ddC) had substantial anti-hepatitis B virus (HBV) activity in vitro compared to 2',3'-dideoxycytidine (ddC) (Hostetler et al. (1994) Antiviral Res. 24, 59-67). Upon administration of liposomal phosphatidyl-ddC to mice, a 40-fold higher drug area under curve was observed in the liver. To evaluate the possibility of using liver-targeted anti-HBV nucleosides to treat woodchuck hepatitis virus, we wanted to find the most potent and selective lipid conjugates. It has been shown that 2',3'-dideoxy-3'-thiacytidine as a racemic mixture of the cis-isomer (cis-(+/-)-BCH-189) has much greater activity against HBV viruses than ddC in vitro. Recently, it was shown that the (-)-beta-L-enantiomer (3TC) is more active and less toxic than the (+)-beta-D-form ((+)-BCH-189). To determine whether phospholipid conjugates of 3TC retain antiviral activity in 2.2.15 cells as demonstrated previously with ddC, we synthesized the 1,2-dipalmitoyl-sn-glycerol-3-phosphate conjugates of (+/-)-BCH-189 and 3TC and assessed their anti-HBV and anti-HIV activities, in vitro. Phosphatidyl-3TC and phosphatidyl-BCH-189 had antiviral activity comparable to the respective free drugs in 2.2.15 cells which chronically produce HBV. In HIV-1-infected human peripheral blood mononuclear cells and HT4-6C cells, phosphatidyl-3TC and phosphatidyl-(+/-)-BCH-189 exhibited significantly lower activity than the corresponding free nucleosides. In view of the documented ability of phosphatidyl-ddC to target drug to the liver, it seems reasonable to expect that phosphatidyl-3TC or phosphatidyl-(+/-)-BCH-189 could be employed to provide greatly enhanced hepatic antiviral activity in HBV infection in vivo.
 ...
PMID:Phosphatidyl-2',3'-dideoxy-3'-thiacytidine: synthesis and antiviral activity in hepatitis B-and HIV-1-infected cells. 858 65

The sodium salts of some hetaryls of the quinoxalin-2-ones 2-4, phthalazine-1,4-dione 5, phthalazin-1-one 6, and pyridazin-6-ones 7 and 8 were alkylated with (+/-) 2,3-O-isopropylidene-1-O-(4-toluenesulfonyl)glycerol (1) to give the respective tetraseco-nucleosides 9-15. Their deisopropylidenation with 70% acetic acid in water gave the corresponding 2,3-dihydroxyprop-1-yl hetaryls 16-22. Compounds 16-22 showed varying inhibition activity against Hepatitis B virus (HBV) with low to moderate cytotoxicity, where 18 and 21 showed the highest replication inhibition and low cytotoxicity.
 ...
PMID:Synthesis and anti-hepatitis B virus activity of some 2,3-dihydroxyprop-1-yl unnatural hetaryls. 1052 Mar 3

Acyclovir triphosphate is a potent inhibitor of hepatitis B virus DNA polymerase, but acyclovir treatment provides no benefit in patients with hepatitis B virus infection. This is due in part to the fact that hepatitis B virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. We synthesized 1-O-octadecyl-sn-glycero-3-phospho (3-P)-acyclovir and found that it was highly active in reducing hepatitis B virus replication in 2.2. 15 cells, while acyclovir was inactive. The greater antiviral activity of 1-O-octadecyl-sn-glycero-3-P-acyclovir appeared to be due to liver cell metabolism of the compound to acyclovir monophosphate (K. Y. Hostetler et al., Biochem. Pharmacol. 53:1815-1822, 1997). However, a closely related compound without a hydroxyl group at the sn-2 position of glycerol, 1-O-hexadecylpropanediol-3-P-acyclovir, was more active and selective in 2.2.15 cells in vitro. In this study, we treated woodchucks chronically infected with woodchuck hepatitis virus with increasing oral doses of 1-O-hexadecylpropanediol-3-P-acyclovir and assessed the response to therapy versus acyclovir or a placebo. At a dosage of 10 mg/kg of body weight twice a day, the test compound significantly inhibited viral replication in vivo, as indicated by a 95% reduction in serum woodchuck hepatitis virus DNA levels and by a 54% reduction in levels of woodchuck hepatitis virus replicative intermediates in the liver. Higher doses were somewhat less effective. In contrast, 20 mg of acyclovir/kg twice daily, a 5. 3-fold-higher molar dosage, had no demonstrable activity against woodchuck hepatitis virus. Oral 1-O-hexadecylpropanediol-3-P-acyclovir appeared to be safe and effective in chronic woodchuck hepatitis virus infection.
 ...
PMID:Antiviral activities of oral 1-O-hexadecylpropanediol-3-phosphoacyclovir and acyclovir in woodchucks with chronic woodchuck hepatitis virus infection. 1085 62

We here presented evidence that a 94-kDa glucose-regulated protein (GRP94) was associated with hepatitis B viral (HBV) polymerase in the human liver cell HepG2 and this association could be applied even in Escherichia coli. We investigated the role of GRP94 in the expression and stabilization of HBV polymerase in Escherichia coli by coexpression of the two proteins. The affinity column-purified glutathione S-transferase-tagged HBV polymerase (GST-P, 130 kDa) showed a proper molecular size and reverse transcriptase activity on several exogenous templates and was sensitive to specific inhibitors. The GST-P was associated with the maltose-binding protein-tagged GRP94 (MBP-GRP94, 130 kDa) using analyses by an affinity chromatography, native gel electrophoresis and glycerol gradient centrifugation. However, nondenaturing and partially denaturing activity gel analyses showed two active bands of approximately 260 kDa and approximately 130 kDa, respectively. Furthermore, in the presence of the encapsidation signal RNA template (HBV epsilon RNA), the approximately 260-kDa active band was gradually converted to approximately 130 kDa, which implies that HBV polymerase was dissociated from the chaperone GRP94 and bound preferentially to the HBV epsilon RNA. These results suggested that the chaperone GRP94 was necessary for the stabilization and production of HBV polymerase as an active form.
 ...
PMID:Expression of stable hepatitis B viral polymerase associated with GRP94 in E. coli. 1096 39


1 2 3 Next >>