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)

2',3'-Dideoxy-3'-thiacytidine (cis-(+/-)-SddC) was found to have potent activity against hepatitis B virus and human immunodeficiency viruses in culture. Recent studies by us identified (-)-SddC as the stereoisomer responsible for the antiviral effect and showed that the cytotoxicity was mainly caused by (+)-SddC. Metabolism studies showed that these drugs were converted to their monophosphates, diphosphates, and triphosphates. The enzyme responsible for the formation of monophosphates was identified to be cytoplasmic deoxycytidine kinase in CEM cells. Uptake studies showed that the intracellular concentration of (-)-SddC and its metabolites was approximately 5-fold higher than that of (+)-SddC metabolites. (-)-SddCTP was more potent than (+)-SddCTP in inhibiting hepatitis B virus replication; (+)- and (-)-SddCTP exhibited minimal inhibition on polymerases alpha and delta, more inhibition on beta, and strong inhibition on gamma. In all cases, (+)-SddCTP was found to be more inhibitory than (-)-SddCTP to all four polymerases. (+)-SddCMP competed with dCTP for incorporation into DNA by DNA polymerase gamma and beta and served as a chain terminator; however, similar incorporation was not detected using other polymerases. The selective inhibition of DNA synthesis in isolated mitochondria by (+)- and (-)-SddCTP suggests a stereospecificity on the mitochondrial uptake of deoxynucleoside triphosphates.
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PMID:Biochemical pharmacology of (+)- and (-)-2',3'-dideoxy-3'-thiacytidine as anti-hepatitis B virus agents. 133 Oct 54

Seven immortalized B cell clones, five of which secreted specific human monoclonal antibodies (MAbs) against hepatitis B, tetanus toxoid, and Rhesus D antigens, were evaluated for their susceptibility to infection by human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Infection was confirmed in three human MAb-producing lines by detection of infectious virus and p24 antigen in culture supernates, by immunofluorescence, and by detection of viral DNA in cells by polymerase chain reaction. The infectable lines were as susceptible to HIV-1 infection as several T cell lines and remained persistently infected for several months, but in contrast to T cell controls, viral cytopathic effects were not observed. Levels of unintegrated viral DNA in the HB1 B cell line were significantly lower than in the HUT78 T cell line. Cell lines that were susceptible to HIV expressed HLA DR, CD20, and CD21, whereas the uninfectable cell lines did not express any of the markers tested. CD4 was undetectable or present on a small percentage of cells in two of the infectable cell lines. However, infection with HIV-1 was blocked more efficiently in B cells than in T cells by soluble CD4, anti-CD4 MAb, and dextran sulphate. The effect of HIV infection on human MAb secretion was variable, being reduced on a per-cell basis in one line, increased in another, and unchanged in a third.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Susceptibility of human monoclonal antibody-producing B cell lines to infection by human immunodeficiency virus. 133 86

2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) is a nucleoside analog that selectively inhibits human immunodeficiency and hepatitis B viruses in vitro. In this study, the preclinical pharmacokinetics of racemic FTC in rhesus monkeys following intravenous and oral administration were characterized. The terminal half-life of FTC was independent of the route of administration and averaged 1.34 +/- 0.18 h (mean +/- standard deviation). Total clearance of FTC was moderate to high, averaging 1.49 +/- 0.24 liters/h/kg. Qualitative assessment of urine samples suggests that renal excretion of unchanged FTC was the major route of elimination of the nucleoside. The compound was also eliminated by metabolism and the deaminated biotransformation product 2,3'-dideoxy-5-fluoro-3'-thiauridine (FTU) was detected in serum and urine. This metabolite has no antiviral activity in human lymphocytes and liver cells. FTC and the metabolite FTU were conjugated, to a minor extent yielding the corresponding glucuronides. No 5-fluorouracil was detected in serum or urine. This is consistent with chromatographic studies using a chiral column that indicated that when racemic FTC is treated with cellular cytidine-deoxycytidine deaminase, the D-(+)-enantiomer of FTC is slowly deaminated to D-(+)-FTU, whereas the L-(-)-enantiomer is essentially resistant to this enzyme. The steady-state volume of distribution of FTC in serum averaged 2.23 +/- 0.42 liters/kg, and the nucleoside analog was distributed into the cerebrospinal fluid, which suggests that this drug penetrated the blood-brain barrier. Absorption of FTC after oral administration was rapid, with bioavailability averaging 73 +/- 6%. Taken together, the results indicate that the unusual L-(-)-enantiomer of FTC should be evaluated further in rhesus monkeys prior to determination of whether this compound is useful for treatment of human immunodeficiency and hepatitis B virus infections.
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PMID:Pharmacokinetics and metabolism of racemic 2',3'-dideoxy-5-fluoro-3'-thiacytidine in rhesus monkeys. 133 46

This paper examines the debate over the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) from an historical perspective. The changing criteria for proving the link between putative pathological agents and diseases are discussed, beginning with Robert Koch's research on anthrax in the late nineteenth century. Various versions of 'Koch's postulates' are analyzed in relation to the necessity and sufficiency arguments of logical reasoning. In addition, alterations to Koch's postulates are delineated, specifically those required by the discovery of rickettsiae and viruses in the early twentieth century and by the immunological testing developed after mid-century to demonstrate the links between elusive viral agents and two diseases, hepatitis B and infectious mononucleosis. From this perspective, an examination of the AIDS debate is constructed. Molecular biologist Peter Duesberg's argument that HIV is not the cause of AIDS is analyzed in light of his contention that a version of Koch's postulates has not been satisfied. Additional research findings through 1990 relating to the etiology of AIDS are also noted.
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PMID:Koch's postulates and the etiology of AIDS: an historical perspective. 134 26

The objective was to estimate the probability of sporadic hepatitis B virus (HBV) and human immunodeficiency virus (HIV) transmission to a patient from an infected surgeon due to percutaneous injury during an invasive procedure. Risk was estimated based on a model involving three probabilities: A, the probability that the surgeon will sustain a percutaneous injury during an invasive procedure; B, the probability that the sharp object causing the injury and now contaminated with the surgeon's blood will contact the patient's wound; and C, the probability that infection would be transmitted to the patient after such an exposure. The probability of transmission during one procedure is p = A x B x C. The probability of transmission to at least one patient during N procedures is 1-(1-p)N. Values for A, B, and C were estimated from prospective studies. The estimated probability of transmission from an infected surgeon to a patient during a single procedure is 0.00024-0.0024% for HIV and 0.024-0.24% for HBV if the surgeon is positive for hepatitis B e antigen (HBeAg). The estimated probability of transmission to at least one patient during 3,500 procedures (estimated to be performed during an HIV-infected surgeon's remaining working life) is 0.81-8.1% for HIV; 57-100% for HBV if the surgeon is an HBeAg carrier. These estimates represent population averages and may not necessarily apply to a particular procedure performed by a particular surgeon, for which the risk may be considerably lower or higher than the estimated average. This risk assessment, which is based on limited data and does not take clusters of transmission into account, predicts that the risk of sporadic HBV transmission from infected surgeons to patients due to percutaneous injury during an invasive procedure is small and that the risk of HIV transmission is less than that for HBV. More data are needed to understand both sporadic and epidemic transmission in order to further reduce patient risk.
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PMID:Risk of hepatitis B and human immunodeficiency virus transmission to a patient from an infected surgeon due to percutaneous injury during an invasive procedure: estimates based on a model. 134 65

The outpatient management of patients infected with human immunodeficiency syndrome is reviewed. Patients with CD4+ cell counts of greater than 0.5 x 10(9)/L (500/mm3) require no specific intervention except vaccination against influenza, pneumococcus, and possibly hepatitis B. They should have a follow-up examination every 3 to 6 months. Because of its success in preventing the progression of the disease, zidovudine (AZT), 100 mg five times per day, is recommended for patients with CD4+ cell counts of less than 0.5 x 10(9)/L (500/mm3). During this stage of the disease, a patient should be seen every 1 to 3 months and monitored for drug toxicity and disease progression. Patients with CD4+ counts of less than 0.2 x 10(9)/L (200/mm3) are at high risk of developing Pneumocystis carinii pneumonia. Prophylaxis with oral trimethoprim-sulfamethoxazole (one double-strength tablet three times weekly) or dapsone (100 mg three times weekly) is recommended. Treatment costs for the patient with CD4+ cells less than 0.5 x 10(9)/L (500/mm3) are at least $3000 per year.
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PMID:Outpatient management of patients infected with human immunodeficiency virus. 134 66

Infection by the human immunodeficiency virus is associated with polyclonal B cell activation and increased levels of serum IgA. In order to characterize the molecular species of serum IgA, we have measured total IgA, IgA1, and IgA2 in sera from 60 HIV-1-infected patients and 40 healthy controls. In addition, secretory IgA (S-IgA), secretory IgM (S-IgM), free immunoreactive secretory component (SC), and the distribution of monomeric and polymeric IgA were determined. The data confirm the elevation of total serum IgA levels in HIV-1-infected patients, and both IgA1 and IgA2 concentrations are elevated. Furthermore, the data show a substantial increase in serum levels of both monomeric and polymeric IgA. Serum S-IgA levels were significantly increased in CDC group II patients versus controls and more frequently elevated in CDC group IV patients. The highest S-IgA levels were found among patients with the lowest blood CD4+ cell counts. Serum S-IgA levels were not correlated with serum levels of either total IgA or polymeric IgA. Serum S-IgM levels were also increased in HIV-1-infected patients and positively correlated with serum S-IgA levels. Conversely, serum levels of free SC were not altered. An increase in serum S-IgA was not related to human hepatitis B virus infection and/or to hepatic dysfunction or to diarrhea or overt intestinal infection. The data indicate that secretory Ig (S-IgM and S-IgA), which are likely to be produced at mucosal sites, increase in the serum of HIV-1-infected patients.
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PMID:Secretory immunoglobulins in serum from human immunodeficiency virus (HIV)-infected patients. 135 13

Some types of reused dental equipment, especially handpieces and their attachments for drilling and cleaning teeth, might be responsible for cross-contamination if patient material were to lodge temporarily in difficult-to-disinfect internal mechanisms. This possibility is worrisome with respect to transmission of hepatitis B and human immunodeficiency viruses (HBV, HIV). Previous cross-contamination studies have relied on laboratory experiments with bacteria or dye tracers. To assess possible risk more thoroughly, we tested 30 new prophylaxis angles and 12 new high-speed handpieces to see whether they would take up and expel contaminants in laboratory and clinical trials. In treatments of three patients, including two infected with HIV, human-specific DNA (beta-globin, HLA DQ alpha) and HIV proviral DNA were detected inside or coming back from the devices. Similarly, when handpieces were operated in contact with blood pooled from HBV-infected patients, HBV DNA was detected in samples taken from inside the equipment and from their attached air/water hoses. When we used bacteriophage phi X174 as a model virus in laboratory tests, many infective viral particles were recovered from internal mechanisms of handpieces, their connecting air/water hoses, and from water spray expelled when the equipment was reused. We recommend that reused high-speed, air-driven handpieces and prophylaxis angles should be cleaned and heat-treated between patients. Further studies are needed to determine ways of eliminating the risks associated with exhaust hoses and air/water input lines.
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PMID:Cross-contamination potential with dental equipment. 809 83

Twenty-six human immunodeficiency virus (HIV)-infected asymptomatic patients with CD4+ lymphocytes > 400 per mm3 were randomly allocated to a range of doses of recombinant gp160 or a control (recombinant hepatitis B vaccine) on a double-blind basis. Each patient received an injection at 0, 4, 12, 24, 36, and 48 weeks. Treatment assignments were decoded when all patients reached 28 weeks of the study period. HIV-1-specific CD4+ and CD8+ cytotoxic T lymphocyte (CTL) activities were assessed in vitro before vaccination and 2 weeks after each injection. There were significant increases in major histocompatibility complex-restricted HIV-1 Env-specific CD4+ and CD8+ CTL activities in 18 of 21 gp160 vaccinees. No control-injected patients showed a significant change. Neither gp160 nor control recipients showed significant changes in HIV-1 Gag- and Pol-specific CTL activities. HIV-1 Env-specific CD4+ and CD8+ CTL precursor frequencies were also measured in three vaccinees before and at 24 weeks after vaccine was started. CTL precursor frequencies also increased in both CD4+ and CD8+ populations. This study shows that this gp160 vaccine is immunogenic in enhancing HIV-1 Env-specific cytotoxic T-cell-mediated immunity in HIV-seropositive individuals.
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PMID:Enhancement of human immunodeficiency virus (HIV)-specific CD4+ and CD8+ cytotoxic T-lymphocyte activities in HIV-infected asymptomatic patients given recombinant gp160 vaccine. 136 Jun 65

Intact surgical gloves are a barrier to hepatitis B virus and human immunodeficiency virus (HIV) but once perforated during surgery they cannot sustain adequate defence. This study examines the rate of glove perforations during surgery at a District General Hospital. In total, 275 pairs of gloves were collected from 100 consecutive operations. In the 43% of gloves that had been damaged 200 perforations were recorded. The mean rate per operation in the surgeon's gloves was 1.18. Injuries to the non-dominant index finger were significantly higher than injuries to other parts of the hand. Injuries occurred particularly during manipulation of the needles and at wound closure. Consultants were more likely to have glove perforation than juniors. Operations requiring manipulation of instruments deep within the wound had a higher rate than those on the surface. The results of the study indicate that a surgeon risks more than one hepatitis B infection per lifetime and that at least one in 1500 surgeons is likely to be infected by HIV during the next 35 years.
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PMID:The mechanisms and risks of surgical glove perforation. 136 7


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