PubMed Health⌕ Search

Biomedical subjects

D N Nosik

Publications and source records attributed to D N Nosik.

35 records · Page 2Linked to original sources

[The inhibiting action of interferon inducers on the multiplication of the human immunodeficiency virus].

High molecular natural (ridostin and larifan) and synthetic (camedon) interferon inducers inhibited HIV-1 replication in MT-4 and CEM cultures when administered simultaneously with the inoculum. The effect of interferon inducers was comparable with that of azidothymidine in concentrations providing cell protection. The degree of culture protection determined by the number of viable and antigen-containing cells was approximately similar for strain 899A and freshly isolated IV39. No significant difference in the efficacy of the preparations in the two different cell cultures. MT-4 and CEM, was observed. It may be assumed that the antiviral effect of the interferon inducers under study will depend little on the type of cell culture.

Acridines↗

[Inhibitors of ADP ribosylation as antiviral agents: an experimental study in a model of HIV infection].

The paper deals with further search for substances modifying metabolic processes, changing the conditions of virus existence in the host cell and, consequently, possessing a certain antiviral activity. The antiviral effects of aromatic carbonic acids amides including trisubstituted benzamides and nicotinamide were tested. Five out of 8 substances tested possessed antiviral activity which might be due to their capacity to inhibit the activity of the enzymes of ADP-ribosylation. By blocking cellular processes of ADP-ribosylation, the substances under study depressed DNA capacity for reparation, inhibited differentiation and transformation of cells, i.e. had an indirect effect on reproduction of viruses. The universal nature of the processes coursing with participation of NAD(+)-dependent ADP-ribosylation suggests that the range of antiviral activity of inhibitors of mono- and poly-ADP-ribosylation would not be limited to HIV infection but would be rather wide.

Adenosine Diphosphate↗

[Cultivation of cells producing the human immunodeficiency virus].

The possibility of optimizing the conditions for the cultivation of cells producing human immunodeficiency virus (HIV) was explored. The stimulating effect on the cell cultures of interleukin-2 and specific anti-interferon antibodies was examined. The individual use of interleukin-2 or anti-interferon antibody preparations did not result in any marked enhancement of HIV virus reproduction in the cells, whereas combining of interleukin-2 which stimulated proliferation of T-lymphocytes with poly- and monoclonal anti-interferon antibodies proved to be effective increasing the expression of virus-specific antigens in the cells 1.5-fold. It seems expedient to carry out further screening of different reagents and combinations thereof capable of significantly increasing HIV virus reproduction in cell cultures which would serve as the antigen for diagnostic systems.

Antibodies↗

[The effect of 3'-azido-3'-deoxynucleosides on the reproduction of AIDS virus in cell culture].

Action of three nucleoside analogues with azido-group on AIDS virus (human immunodeficiency virus--HIV) reproduction was studied in two cell species. Among these compounds there were 3'-azido-3'-deoxythymidine (Az-T), 3'-azido-3'-deoxyarabinothymidine (Az-AT) and 3'-azido-2',3'-dideoxy-5-methylcytidine (Az-dCMe). All compounds prevent cells against HIV infection, but Az-T action was expressed more strongly. The reason for the lower activity of the Az-AT and Az-dCMe bases is probably stipulated by their poor conversion to the corresponding 5'-triphosphates. Az-T 5'-triphosphate blocks HIV reproduction due to the inhibition of the viral reverse transcriptase.

Azides↗

[Inhibition of HIV reproduction in cultured cells using proteolysis inhibitors].

Treatment of AIDS is a complicated problem since there is a limited set of preparations tested and most of them appear to be ineffective. Their main target is HIV reverse transcriptase. The data presented show that proteolysis inhibitors are able to inhibit HIV reproduction in cell culture. The compounds used in this study, gordox and kontrikal, are officinal drugs and therefore it is worthwhile to study their effect in patients with AIDS.

Aprotinin↗

[Inhibition of HIV reproduction in cell culture by 5'-phosphonates of 3'-azido-2',3'-dideoxynucleosides].

The antiviral activity of 3'-azido-2',3'-dideoxynucleoside 5'-phosphate analogues: 5'-phosphonomethylene-3'-azido-2',3'-dideoxythymidine, 5'-methylphosphonate and 5'-phosphite of 3'-azido-2',3'-dideoxythymidine, 5'-phosphites of 3'-azido-2',3'-dideoxyadenosine and guanosine was investigated in HIV-infected cell cultures (human lymphoblastoid cells). The effectivity of inhibition of HIV-reproduction in cells by these substances was close or even higher than that for the corresponding 3'-azido-2',3'-dideoxynucleosides, whereas their toxicity was lower than that of nucleosides. These substances are supposed to be transported into the cells and to be transformed into the corresponding 5'-triphosphate analogues under the action of cell kinases. It is possible that such agents are terminator substrates of virus reverse transcriptases and thus inhibit the biosynthesis of DNA chains.

Antiviral Agents↗

[The search for preparations suppressing the reproduction of the AIDS virus].

Trials of clinically advantageous national inducers, thymus hormones, as well as human recombinant alpha 2-interferon were carried out in cultures of continuous lymphoblastoid cells H9/IIIB infected with HIV virus. The virus-inhibiting effect for HIV was observed with interferon in doses of 10-100 IU/ml. At a concentration of interferon of 1000 IU/ml, virus replication was inhibited completely, the interferon doses used exerting no marked toxic or antiproliferative effect on the cells. Human interferon inducers, poly(G).poly(C), PXL-6, dsRNA in concentrations of 50-100 micrograms/ml inhibited virus reproduction significantly. The highest antiviral effect was achieved with yeast dsRNA. The preparations of immunomodulators, thymarin, the 5th and 7th fractions of thymosin, noticeably stimulated proliferation of infected T-lymphocytes, reducing the relative number of cells carrying the virus-specific antigen. Combined use of preparations with different mechanisms of the antiviral effect may be advantageous in prevention and treatment of AIDS.

Antiviral Agents↗

[Immunoenzyme analysis of monoclonal antibodies on solid-phase infected cells].

Monoclonal MAK-14-7 antibodies to the surface antigen of Venezuelan equine encephalomyelitis virus and OKA series to vaccinia virus antigens were studied by enzyme-immunoassay (EIA) on the solid phase of the infected Vero, BHK-21, and HeLa cells. The immunoglobulins under study from the culture and ascitic fluids of hybridomas were shown to bind specifically with the appropriate antigens of the infected cells. The activity of monoclonal antibodies to viral antigens in EIA on the solid phase of the infected cells was 10-fold higher than in indirect immunofluorescence test. The method has a number of useful advantages such as the simplicity of preparation of the antigen solid phase, rapidly obtainable results, long-term preservation of ready panels with the specific antigen at room temperature. The high sensitivity of the method makes it effectively useful for screening of hybrid clones producing monoclonal antibodies.

Animals↗

[Testing of monoclonal antibodies to human interferon].

A comparative study of testing methods for polyclonal and monoclonal antibodies to human interferon using direct and reverse neutralization of the antiviral activity of interferon as well as ELISA was carried out. The activity of antibodies in ELISA was dozens of times higher than in neutralization tests. Polyclonal antibodies from the sera of mice immunized with alpha 2 interferon had a higher neutralizing capacity. M-5 monoclonal antibodies in specimens of ascitic fluid induced by inoculation of mice with hybrid cells exhibited an increase in both binding and neutralizing activity as compared with specimens of the culture fluid. Immunoglobulins from the ascitic and culture fluid of nonproductive myeloma cells as well as hybridomas producing monoclonal antibodies of other specificities showed practically no reaction with interferon in any of the tests under study. The screening of monoclonal antibodies intended for research and biotechnological purposes requires a composite analysis in both neutralization and binding tests in order to recover purposefully the hybrid clones producing antibodies with both or one of these properties.

Animals↗

[Human immune interferon: production and action].

The most marked production of immune interferon by human peripheral blood leukocytes and splenocytes stimulated with phytohemagglutinin (PHA) and staphylococcal enterotoxin A (SEA) was shown to be achieved when lymphoid cells are propagated under conditions of constant sparing mixing on roller apparatus at a temperature of 37 degrees +/- 0.5 degrees C. The resulting interferon was sensitive to low pH, thermolabile, inactivated by treatment with trypsin, and not neutralised by antisera to human alpha- and beta-interferons. The antiviral properties with regard to vesicular stomatitis and Semliki Forest viruses were practically similar in PHA- and SEA-induced interferon and human alpha- and beta-interferons. The capacity to inhibit colony formation by HeLa cells was 30 times higher in gamma-interferon than the antiproliferative activity of alpha- and beta-interferons.

Animals↗

[Activation of viral reproduction in a mixed infection with human immunodeficiency virus and herpes viruses].

Mutual activation of reproduction of type 1 HIV and herpes simplex types 1 and 2 viruses (HSV) was observed in simultaneous infection of continuous T-cellular lymphoblastoid lines (CEM, 119, Hut-78, MT-4, Jurkat-tat) and U-937 monocytic line. Syncytium formation and cytodestructive pattern of reproduction of viruses of both families in these cell lines necessitated the use of enzyme immunoassay (EIA) to detect the antigens of these viruses in order to assess the level of reproduction. The concentration of HIV antigens in EIA increased in mixed infection by 1.4 to 2.1 times in different cultures in comparison with the culture infected with HIV-1 alone, and concentrations of HSV-1 and HSV-2 increased by 1.3-1.8 times in mixed infection, in comparison with reproduction in lymphoblastoid cultures infected with HSV alone. EIA was alone used to examine the production of IgG and IgM antibodies to Epstein-Barr virus, another representative of Herpesviridae family, in the blood sera of patients with immunodeficiency states in whose sera antibodies to proteins produced by gag HIV gene (p15/17, p24, p55) were detected. Increased concentration of IgG antibodies were revealed in 36% of these patients, whereas in healthy donors the sera with elevated concentrations of IgG to Epstein-Barr virus were far less incident (12%). A hypothesis about mutual activation of HIV and herpes viruses is put forward.

Animals↗

[Study of the anti-HIV activity of miramistin].

The anti-HIV activity of a cationic detergent myramistin and nonionic detergent dezintegron-0 (d-0) was studied using HIV-1 strains III B/H9 and BRU in lymphoblastoid cells MT-4 and Jurkat-tat. Myramistin in a concentration of 0.075 mg/ml was shown to prevent HIV-1 replication in MT-4 when these cells were cocultivated with the cells preinfected and treated with the detergent. Myramistin in concentrations from 0.030 to 0.050 mg/ml delayed the accumulation of virus antigens in the cells by 4 and 14 days, respectively, without preventing the infection of intact cells. Nonionic d-0 prevented HIV-1 infection of intact Jurkat-tat cells at a concentration of 12.5 mg/ml.

Antiviral Agents↗

[The effect of fetal calf serum on the anti-HIV properties of miramistin].

The anti-HIV activity of an antiseptic miramistin in the presence of fetal calf serum (FCS) was studied. It has been recently shown that cation detergent miramistin at a concentration of 100 micrograms/ml prevented HIV-1 replication in MT-4 cells when these cells were cocultivated with MT-4 cells previously infected and treated with the detergent in a protein-free medium. Under such conditions 50 micrograms of miramistin per ml delayed HIV propagation in MT-4 cells by 14 days. Detergent-dependent arrest of HIV development was abolished by addition of FCS at a final concentration of 50%. Miramistin in a dose of 100 micrograms/ml prevents HIV-1 replication in Jurkat-tat cells when they are cocultivated with the cells of the same line previously infected and treated by the detergent in the presence of 5% FCS. FCS in concentrations from 12.5 to 75% prevents the anti-HIV activity of miramistin in a dose of 100 micrograms/ml.

Animals↗

[The isolation and characteristics of monoclonal antibodies to recombinant proteins of HIV-1 and HIV-2--the env and gag gene products].

Ten hybridomas secreting monoclonal antibodies (Mab) against recombinant HIV-1 and HIV-2 antigens were produced (3 Mab anti-gag protein, 2 anti-env1, and 5 anti-env2). In the immunoblotting assay all the anti-gag Mabs reacted with HIV capsid protein p24, whereas one of them reacted also with p55 protein and with 7 other polypeptides. Another anti-gag Mab cross-reacted with the antigen of subpopulation of human peripheral blood lymphocytes. The third one interacted with the antigen of both HIV-1 and HIV-2. All the 10 Mabs interacted with natural HIV antigens and can be used for identification and differentiation of HIV-1 and HIV-2.

Animals↗

[Morphological analysis of a cell system, infected with different strains of the human immunodeficiency virus].

Cell systems infected with 63 strains of types 1 and 2 HIV virus (HIV-1 and HIV-2) were examined under electron microscope. HIV virions were most frequently detected near the cell membrane or budding from it. In the cytoplasm HIV occurred only in vacuole-like formations. Accumulations of mature virions were seen in the cell-to-cell space. Mature particles of HIV-1 and HIV-2 differed by their morphology from oncoviral C particles and were similar rater to the Visna/Medi type Lentiviruses. Morphological analysis of HIV strains isolated in Russia demonstrated their similarity to be foreign HIV strains.

Cell Line↗

[Sensitivity of Russian HIV-1 isolates to anti-HIV agents].

HIV strains isolated from HIV patients hospitalized at the Central Research Institute of Epidemiology in 1991-1993 are analyzed. HIV-1 strains isolated at different stages of the illness were referred to subtypes A and B. The biological properties of the isolates of both subtypes were virtually the same. The majority of the isolated HIV-1 strains were relatively resistant to azidothymidin, no matter whether the patients were previously treated with this drug or not. Study of strains repeatedly isolated from the same patients showed an increase of the cytodestructive characteristics of the isolates. Strains isolated from the same epidemiological chain were characterized by the same properties and sensitivity to the tested antiHIV agents. The resistance of the virus to antiHIV drugs with different mechanisms of action may be an indicator of the terminal stage of the illness.

Acquired Immunodeficiency Syndrome↗