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

Diaspirin crosslinked hemoglobin (DCLHb), a hemoglobin based oxygen carrying solution prepared from outdated human blood, is subjected to a heat treatment step to inactivate viruses in our manufacturing process. To validate the efficacy of this inactivation, we have simulated the heat treatment procedure at a reduced scale using hemoglobin solution spiked with representative viruses. Human Immuno-deficiency Virus (HIV), Cytomegalovirus (CMV), and Duck Hepatitis B Virus (DHBV) were used in this validation. Inoculation with concentrated virus was performed just prior to the heat treatment to determine the effect of that specific process step. Samples were taken before, during, and after heat treatment and assayed for virus titer in an attempt to assess the rate as well as the extent of virus inactivation. CMV was analyzed in a plaque assay using MRC-5 indicator cells. The titer was reduced from 3.3 x 10(6) plaque forming units (PFU) per mL to less than 5 x 10(1) PFU/mL (detection limit) within 30 minutes. DHBV was analyzed by inoculation of serially diluted samples into Pekin ducklings, followed at intervals by screening sera for DHBV DNA by dot blot hybridization. The titer was reduced from 5.0 x 10(6) duck infectious units (DIU) per mL to less than 5 x 10(0) DIU/mL (detection limit) within 1 hour. HIV titers were determined through an ELISA assay for p24 antigen present in peripheral blood lymphocyte cocultivation supernatants. The titer was reduced from 2.0 x 10(4) infectious units (IU) per mL to less than 2 x 10(0) IU/mL (detection limit) within 1 hour. These data indicate that high titers of these blood borne viruses are rapidly inactivated by this heat treatment process.
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PMID:Validation of virus inactivation by heat treatment in the manufacture of diaspirin crosslinked hemoglobin. 132 42

Several vaccinia virus recombinants inducing the synthesis of the middle surface (M) protein of hepatitis B virus (HBV) were constructed. One of them, denoted v137, was examined in some detail. The virus replicated nearly to the same extent in various cell lines, viz. human embryo diploid fibroblast LEP and MRC-5 cells, rabbit embryo fibroblast REF cells, TK- rat RAT-2 cells, and green monkey CV-1 cells. However, the production of M protein was found considerably lower in the human LEP and MRC-5 than in the other cells examined. In addition, the kinetics of M formation were different in these two cell systems, LEP cells lagging significantly behind CV-1 cells. The low-level production of M protein in LEP cells was not increased by repeated v137 passages in LEP cells, nor by a passage in a laboratory worker accidentally infected with the v137 virus, nor by shortening the leader sequence preceding the translation initiation codon. The greater part of the M antigen was found to be cell associated, more so in the cells of human than monkey origin. From the major HBV S antigen (HBsAg) isolated from the plasma of chronically infected subjects, the antigen released by cell destruction differed by binding to polymerized human albumin. This property was utilized in ELISA to detect anti-preS2 antibody. Rabbits inoculated intradermally with the v137 virus developed antibodies reactive in this assay as well as with a synthetic peptide corresponding in the amino acids 14-34 of the NH2 terminus of the HBsAg preS2 region.
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PMID:A recombinant vaccinia virus expressing hepatitis B virus middle surface protein. Restricted expression of HBV antigens in human diploid cells. 237 67

Several novel 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D- arabinofuranosyl)pyrrolo[2,3-d]pyrimidines have been synthesized and evaluated for their anti-human cytomegalovirus (HCMV), anti-hepatitis B virus (HBV), and anti-herpes simplex virus (HSV) activities in vitro. These nucleosides were prepared starting from 2-amino-4-chloro-7-(2-deoxy-2-fluoro- 3,5-di-O-benzoyl-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (3), which in turn was synthesized by direct glycosylation of the sodium salt of 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (1) with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide (2). Displacement of the 4-chloro group of 3 with OH, NH2, NHOH, SH, and SeH nucleophiles furnished the corresponding nucleosides 6-8, 12, and 14, respectively. The 3'-deoxygenation of 2-amino-4-chloro-7- (2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (4) and subsequent amination gave 2,4-diamino-2',3'-dideoxy derivative 19. Catalytic hydrogenation of 3 followed by debenzoylation afforded 2-aminopyrrolo[2,3-d]pyrimidine nucleoside 23. Among the compounds evaluated for their ability to inhibit the growth of HCMV (strain AD169) in MRC-5 cells using a plaque reduction assay, only 7 was significantly active in vitro with a 50% inhibitory concentration (IC50) of 3.7 micrograms/mL (TI > 125), whereas the IC50 value of ganciclovir (DHPG) was 3.2 micrograms/mL. Strain D16 of HCMV was more resistant to 7 (IC50 11 micrograms/mL) than the AD169 strain. When 7 was tested in combination with DHPG, the resultant anti-HCMV activity was found to be moderately synergistic with no evidence of antagonism. Nucleoside 7 also reduced episomal HBV replication in human hepatoblastoma 2.2.15 cells with an IC50 of 0.7 micrograms/mL (TI > 143). Development of cells harboring HBV which had become resistant to the drug was not observed with 7. Compound 7 also exhibited significant activity against herpes simplex virus types 1 and 2 (IC50 of 4.1 and 6.3 micrograms/mL, respectively) in Vero cells.
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PMID:Synthesis and anti-DNA viral activities in vitro of certain 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d d pyrimidine nucleosides. 756 29

The carbocyclic analog of 2'-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because of recent observations with other nucleoside analogs that biological activity may be associated the L enantiomer rather than, as expected, with the D enantiomer, we have studied the metabolism of both enantiomers of CdG to identify the enzymes responsible for the phosphorylation of CdG in noninfected and virally infected human and duck cells. We have examined the enantiomers as substrates for each of the cellular enzymes known to catalyze phosphorylation of deoxyguanosine. Both enantiomers of CdG were substrates for deoxycytidine kinase (EC 2.7.1.74) from MOLT-4 cells, 5'-nucleotidase (EC 3.1.3.5) from HEp-2 cells, and mitochondrial deoxyguanosine kinase (EC 2.7.1.113) from human platelets and CEM cells. For both deoxycytidine kinase and mitochondrial deoxyguanosine kinase, the L enantiomer was the better substrate. Even though the D enantiomer was the preferred substrate with 5'-nucleotidase, the rate of phosphorylation of the L enantiomer was substantial. The phosphorylation of D-CdG in MRC-5 cells was greatly stimulated by infection with human cytomegalovirus. The fact that the phosphorylation of D-CdG was stimulated by mycophenolic acid and was not affected by deoxycytidine suggested that 5'-nucleotidase was the enzyme primarily responsible for its metabolism in virally infected cells. D-CdG was extensively phosphorylated in duck hepatocytes, and its phosphorylation was not affected by infection with duck hepatitis B virus. These results are of importance in understanding the mode of action of D-CdG and related analogs and in the design of new biologically active analogs.
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PMID:Metabolism in human cells of the D and L enantiomers of the carbocyclic analog of 2'-deoxyguanosine: substrate activity with deoxycytidine kinase, mitochondrial deoxyguanosine kinase, and 5'-nucleotidase. 959 24

Diploid cells (WI-38, MRC-5) vaccines have their origin in induced abortions. Among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis A, chickenpox, and herpes zoster. Nowadays, other abortion tainted vaccines cultivated on transformed cells (293, PER.C6) are in the pipeline: flu, Respiratory Syncytial and parainfluenza viruses, HIV, West Nile virus, Ebola, Marburg and Lassa, hepatitis B and C, foot and mouth disease, Japanese encephalitis, dengue, tuberculosis, anthrax, plague, tetanus and malaria. The same method is used for the production of monoclonal antibodies and other proteins, gene therapy and genomics. Technology enables us to develop the aforementioned products without resorting to induced abortion. Full disclosure of the cell origin in the labelling of vaccines and other products must be supported. There are vaccines from non-objectionable sources which should be made available to the public. When no alternative vaccines exist, ethical research must be promoted. Non-objectionable sources in the production of monoclonal antibodies, gene therapy and genomics must be encouraged. It is not be consistent to abstain from products originated in embryonic stem cells and at the same time approve of products obtained from induced abortions. It is of paramount importance to avoid that induced abortion technology seeps into every field of Medicine.
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PMID:[Vaccines, biotechnology and their connection with induced abortion]. 1861 Oct 78

The new antivirals clevudine, telbivudine and emtricitabine may be potent agents for the treatment of hepatitis B virus (HBV). However, there have been no reports on serious adverse events associated with the use of clevudine. A son and his mother both had HBV infection (ages: 27 and 47 years, respectively), and they had received antivirus treatment with clevudine (30 mg daily). They developed progressive weakness of the lower extremities and difficulty arising from the ground. Both the patients had symptoms for the previous 3 approximately 4 months in process of 14 approximately 17 months of clevudine therapy. The physical examinations showed positive Gower's sign, a decreased gait velocity and symmetrical proximal weakness (MRC grade 4/5). Their blood tests at admission revealed elevated or positive HBs Ag, HBV DNA, AST, ALT, creatine kinase, LDH, myoglobin and CK-MB. For both patients, the electrodiagnostic studies indicated myopathy and the pathologic findings of biopsied muscles revealed myositis. Drug-induced polymyositis was suspected and the clevudine was finally withdrawn. The muscle weakness and laboratory findings were improved for both patients after conservative care. We report here on the first cases of polymyositis that may have been caused by administering the new nucleoside analog clevudine for treating HBV infection.
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PMID:Polymyositis in patients taking antiviral clevudine therapy: a report of two cases. 2020 82

The present work is focused on the development and evaluation of single dose sustained-release Hepatitis B surface antigen (HBsAg) loaded nanovaccine for Hepatitis B. The conventional treatment suffers from repeated administration and hence requires a booster dose. Therefore, polymeric nanovaccine of HBsAg was developed by double emulsion solvent evaporation technique, utilizing central composite design for formulation optimization. The effects of independent variables (like polymer amount, stabilizer concentration, aqueous/organic phase ratio and homogenizer speed) were also studied on critical quality attributes like particle size and entrapment efficiency. Nanovaccine was characterized in terms of physicochemical parameters, release, internalization and in vivo immunological evaluation in BALB/c mice after administration by different routes such as oral, sub-cutaneous, nasal and intramuscular. The designed nanovaccine demonstrated nanometric size with smooth surface, negative zeta potential, maximum entrapment, sustained release and better internalization in macrophage and MRC-5 cell line. The immune-stimulating activity of nanovaccine administered by different routes was evaluated by measuring anti-HBsAg titre like specific immunoglobulin IgG and IgA response and cytokine level (interleukin-2, interferon-Y) measurement. The results indicated that the nanovaccine administered by intramuscular route produced better humoral as well as cellular responses and potential carriers for antigen delivery at single dose administration via intramuscular route.
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PMID:Rational design and evaluation of HBsAg polymeric nanoparticles as antigen delivery carriers. 2934 54