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Biomedical subjects

H Bugany

Publications and source records attributed to H Bugany.

12 recordsLinked to original sources
PubMed2001

Infection and activation of monocytes by Marburg and Ebola viruses.

In this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. Our data showed that monocytes are permissive for both filoviruses. As is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus replication. The activation was triggered similarly by Marburg and Ebola viruses, species Zaire and Reston, as indicated by the release of the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-6 as well as the chemokines IL-8 and gro-alpha. Our data suggest that infected monocytes may play an important role in the spread of filoviruses and in the pathogenesis of filoviral hemorrhagic disease.

Animals↗
PubMed1996

Filovirus-induced endothelial leakage triggered by infected monocytes/macrophages.

The pathogenetic mechanisms underlying hemorrhagic fevers are not fully understood, but hemorrhage, activation of coagulation, and shock suggest vascular instability. Here, we demonstrate that Marburg virus (MBG), a filovirus causing a severe form of hemorrhagic fever in humans, replicates in human monocytes/macrophages, resulting in cytolytic infection and release of infectious virus particles. Replication also led to intracellular budding and accumulation of viral particles in vacuoles, thus providing a mechanism by which the virus may escape immune surveillance. Monocytes/macrophages were activated by MBG infection as indicated by tumor necrosis factor alpha (TNF-alpha) release. Supernatants of monocyte/macrophage cultures infected with MBG increased the permeability of cultured human endothelial cell monolayers. The increase in endothelial permeability correlated with the time course of TNF-alpha release and was inhibited by a TNF-alpha specific monoclonal antibody. Furthermore, recombinant TNF-alpha added at concentrations present in supernatants of virus-infected macrophage cultures increased endothelial permeability in the presence of 10 micron H2O2. These results indicate that TNF-alpha plays a critical role in mediating increased permeability, which was identified as a paraendothelial route shown by formation of interendothelial gaps. The combination of viral replication in endothelial cells (H.-J. Schnittler, F. Mahner, D. Drenckhahn, H.-D. Klenk, and H. Feldmann, J. Clin. Invest. 19:1301-1309, 1993) and monocytes/macrophages and the permeability-increasing effect of virus-induced cytokine release provide the first experimental data for a novel concept in the pathogenesis of viral hemorrhagic fever.

Base Sequence↗
PubMed1992

[Studies on HIV inactivation in allogeneic bone transplants using chemical disinfection and radioactive irradiation].

In our study we examined bone disinfection by ethanol and by irradiation. A 70% aqueous ethanol solution diffused through a 3 mm and a 6 mm slice of human cancellous bone against 2 ml of a HIV-sample (RTA: 300,000 cpm/ml) for 24 hours. In both cases HIV could not be inactivated. Infected T-lymphocyte cultures showed specific morphological cell changes. The Abbott HIV-antigen-EIA proved the treated HIV-samples to be infectious after cultivation in macrophage-cultures. Additional gas chromatography measurements of ethanol diffusion through 3 mm and 6 mm of human cancellous bone supported these observations: a 70% aqueous ethanol solution achieved a concentration of 25.6% (18.0%) in median after 24 hours and a thickness of 3 mm (6 mm). The effect of different doses of irradiation on HIV-samples (RTA:300,000 cpm/ml) was examined. The samples were irradiated with 2, 7, 10, 15 and 25 kGy to determine the appropriate dose for inactivation. Irradiation with 15 kGy caused HIV inactivation since no virus production could be detected in the macrophage culture (Abbott HIV-antigen-EIA). The samples irradiated with 2, 7 and 10 kGy were still infectious.

Bone Transplantation↗
PubMed1988

Inhibition of natural killer cytotoxicity by extracellular ppp(A2'p5')nA oligonucleotides.

The effect of purified 2'-5' linked polyadenylated oligomers on the human natural killer (NK) activity has been investigated. Permeabilization of NK cells to ppp(A2'p5')2A did not enhance their NK activity at any concentration tested. Furthermore, concentrations higher than 0.1 mM inhibited their NK activity. Similar results were obtained by pre-incubating non-permeabilized intact cells, indicating an extracellular effect of these compounds on cell membranes, which was further investigated. This inhibition by the oligomers was greater (50% inhibition was obtained with 50 micron), when they were added directly to the NK assay, than when the NK cells were pre-incubated. Similar inhibitory effects were observed with ppp(A2'p5')A and ppp(A2'p5')3A oligomers but not with the dephosphorylated "core" molecules or other nucleotides. The inhibition was completely or partially reversed by phorbol esters and by interferon (IFN), respectively. The inhibition was temperature and extracellular Ca2+ dependent. The oligomers did not inhibit the binding of the effector cells to the target cells. The programming for lysis was the step of the lytic mechanism affected, possibly due to the alteration of the Ca2+ influx into the NK cells observed in presence of the ppp(A2'p5')nA.

Adenine Nucleotides↗
PubMed1984

pppA2'p5A' blocks vesicular stomatitis virus replication in intact cells.

pppA2'p5'A blocked the production of infectious vesicular stomatitis virus in HeLa cells. When this compound was present from the beginning of infection, a selective inhibitory effect was observed in viral protein synthesis. Thus, cellular translation was not affected even after 10 h of incubation with this compound, and the bulk of viral proteins was not synthesized. However, this effect was not observed with ATP, GTP, or the core A2'p5'A. The step blocked by pppA2'p5'A is located early during virus infection, but adsorption, entry, and virus uncoating seemed to be unaffected by this compound. Analysis of the antiviral spectrum of pppA2'p5'A indicated that it is active against poliovirus, encephalomyocarditis virus, and Semliki Forest virus and shows no effect against herpes simplex virus type 1 and adenovirus type 5.

Adenine Nucleotides↗
PubMed1983

Inhibition of Rous sarcoma virus assembly by treatment with 2',5' adenosine nucleotides.

We have investigated the influence of 2',5' adenosine nucleotides on the replication and transformation of cells by Rous sarcoma virus (RSV). Treatment with the nucleotides ppp2',5'A4 and 2',5'A4 causes a striking reduction (50-fold) in the yield of infectious progeny virus, while ppp2',5A2 and 2',5'A3 had virtually no effect. The reduction in infectivity seen with 2',5'A4 nucleotides is paralleled by a smaller but significant (three- to four-fold) reduction in the amount of particles released as measured by reverse transcriptase activity and levels of viral structural proteins. The reduced infectivity of released particles is not due to viral RNA being missing since the amount of genomic RNA in particles from 2',5'A4-treated cultures was likewise only reduced by a factor of 2-3. Pulse-chase radioactive label experiments showed that processing of both viral group-specific antigens (gag) and viral envelope glycoprotein (env) gene products was completely normal in nucleotide-treated cultures, but that the rate of appearance of viral proteins in mature virus in the culture supernatants was reduced by a factor of about 3-4. Taken together, the data show that assembly of viral structural proteins into virions which can be released into the medium is slowed, and that assembly of virus particles with reduced infectivity follows upon nucleotide treatment. This inhibition of infectious virus production takes place without significant toxic effects on the cell; host protein synthesis is only 20% inhibited. There is also no significant effect on the secretory ability of the cells as measured by total protein release into the medium or release of fibronectin. The transformed cell phenotype was also subtly affected by 2',5'A4, but not by other oligomers. Plasminogen activator protease activity was sharply reduced upon treatment, while other typical features of RSV-transformed cells such as elevated hexose transport, and pp60src-associated protein phosphokinase activity, were little affected.

Adenine Nucleotides↗
PubMed1977

Binding of the partially purified glucocorticoid receptor of rat liver to chromatin and DNA.

The binding of the glucocorticoid receptor of rat liver to chromatin and DNA has been studied with crude and partially purified preparations of cytosol receptor labelled with [3H]-triamcinolone acetonide in vitro. The use of crude preparations of receptor and increasing protein concentrations leads to an apparent saturation of chromatin and DNA, suggesting a limited number of high affinity nuclear acceptor sites for the receptor. Appropriate controls indicate that the observed saturability of chromatin acceptor sites is due to the presence in crude receptor preparations of heat-stable protein factors which interfere with the binding of the receptor to the genome; whereas the apparent saturation of DNA is due to contamination with deoxyribonucleases. If the activated complex of receptor and triamcinolone acetonide (R-TA) is partially purified to a step where it is free from nucleases and inhibitors, its binding to both chromatin and DNA is linearly dependent on the concentration of free (R-TA) in the incubation medium. There is no absolute specificity with respect to the source of DNA or chromatin, although liver chromatin has considerably higher receptor binding capacity than chromatin from avian erythrocytes. The rate kinetics of association and dissociation for the binding of (R-TA) to DNA and chromatin are very similar, but DNA exhibits a 10-fold higher receptor binding capacity than chromatin. These data, in conjunction with the effect of poly-(D)-lysine and and NaCl on the binding of (R-TA) to chromatin and DNA, suggest that most of the receptor molecules bound to chromatin in vitro interact with the "accessible" DNA stretches. Although a small population of receptor molecules may bind specifically to target tissue genome, the detection of these specific sites against the background of unspecific binding is not possible with unfractionated chromatin or DNA preparations.

Animals↗