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Biomedical subjects

L N Pokidysheva

Publications and source records attributed to L N Pokidysheva.

At least 19 recordsLinked to original sources

[New nucleoside conjugates with phospholipids: synthesis of anti-HIV activity of rac-1-hexadecyl-2-acyl-sn-glycero-3-phosphonucleosides].

New nucleoside-phospholipid conjugates were synthesized based on 1,2-disubstituted glycerides and nucleosides. These contain rac-1-hexadecyl-2-palmitoyl(or 2-methylcarbamoyl)-sn-glycero-3-phosphate as the phospholipid component and 2',3'-didehydro-3'-deoxythymidine, 1-(Z-5-hydroxypentene-2-yl)thymine, or 2',3'-isopropylideneuridine as a nucleoside component. The conjugates were synthesized by three different ways: from rac-1-hexadecyl-2-acyl-sn-glycero-3-phospodichlorides, -3-phosphatidic acids, or -3-H-phosphonates. When subjected to mild alkaline hydrolysis, conjugates containing a 2-palmitoyl group formed conjugates with the lysophospholipid component that had not yet been described. All the conjugates obtained were amorphous compounds stable at room temperature. Their hemolytic and anti-HIV activities were determined. Some conjugates were found to completely inhibit in vitro HIV-1 reproduction in lower doses than the corresponding nucleosides.

Anti-HIV Agents↗

[Stimulation of the inhibiting effect of interferon on the growth of ascitic carcinoma in relation to host responsiveness and cells].

When Krebs-2 ascitic carcinoma is transplanted to mice, administration of interferon may produce either a stimulating or an inhibiting effect on replication of carcinoma cells in the peritoneal cavity depending on the responsiveness of mice (intact or vaccinated with Newcastle disease virus) and the state of the transplanted cells ("common" or "tolerant"). Parallelism was observed in changes of the intensity of cell multiplications and indices of their enzymatic activity under the influence of exogenic interferon.

Animals↗

[The HTHIV27 highly productive continuous cell line and its use for solving the fundamental and applied problems of HIV infection].

For the first time the detailed description of continuous cell line HTHIV27, remaining stable for more than 10 years, has been made. The stability of all biological characteristics and high productivity of the strain has made it possible to use it as a HIV producing strain for the construction of a diagnostic test system for the detection of antibodies to HIV. The lysate obtained on the basis of HIV producing cells HTHIV27 has been shown to possess a number of advantages in comparison with the analogous system based on lytically infected cells. On the basis of strain HTHIV27 an in vitro cell system for the analysis of the specific activity of chemotherapeutic preparations intended for the inhibition of HIV has been developed. The use of this newly obtained continuous cell line HTHIV27 has been shown to permit the evaluation of the antiviral activity of compounds, characterized by different molecular mechanisms for the suppression of viral activity.

Anti-HIV Agents↗

[Cryomethod of concentrating interferon (author's transl)].

The fact of non-simultaneous thawing of protein and water was used for concentration of interferon from pre-frozen preparations. As thawing proceeded, 5 sequential fractions equal in a volume were removed from preparations of human leucocyte, mouse macrophage and tissue chick interferons; the titers of their antiveral activity in the first fraction were 4--8-fold higher than the initial titer, and this activity decreased gradually to a titer which was 2-fold lower than the initial in the fifth fraction. The total amount of interferon units in all the fractions was 1.8--3.8-fold higher than in the initial preparation taken in a volume corresponding to the total volume of all the fractions. As addition of the Vth fraction to the Ist fraction reduced the titer of interferon in it to the initial level, it is suggested that in interferon preparations there is an inhibitor of its effect, "anti-interferon".

Animals↗

[Differences in the antiviral and antioncogenic action of interferons produced in murine peritoneal cells and in Krebs-2 ascitic carcinoma cells].

Comparisons of native preparation of mouse interferons, "macrophage" and "Krebs" revealed some differences, Thus, the minimal time necessary for the development of resistance to vesicular stomatitis virus (VSV) in L cells treated with "macrophage" and "Krebs" interferon was 5 and 2 hours, respectively. The activity of the lysosomal enzyme of acid phosphatase was considerably higher in the cells treated with "Krebs" interferon and infected with VSV than with "macrophage" interferon. Differences in the antiviral and antioncogenic properties of fractions No. 1 and No. 5 of these interferons obtained in fractionation of native interferon preparations by the cryomethod were demonstrated. In particular, fraction No. 5 of "Krebs" interferon, in contrast to that of "macrophage" interferon, had no antioncogenic properties but did have antiviral properties. It is suggested that these differences are due to the presence in native preparations of different substances capable of exerting an effect on interferon.

Acid Phosphatase↗

[Relationship of the characteristics of the chromosome set in human cell cultures to the production and antiviral action of interferon].

The role of chromosomes 2, 5, 16, and 21 in production and effect of human interferon was checked in human diploid cells, human heteroploid cells J-96 and clone J-41 thereof. The J-41 cells were found to have a lower number of chromosomes 2 as compared to the other cells under study; J-41 cells produce less interferon than the other cells. Most J-41 cells lack chromosome 21. Unlike the other two cell cultures, these cells do not produce antivirus state after treatment with interferon. The number of chromosomes 16 is larger in J-96 cells than in diploid ones, and they are less sensitive to interferon than diploid cells. The experimental results confirm the importance of chromosome 2 for coding for interferon production, other chromosomes taking part in the regulation of this process. The gene of sensitivity to interferon is localized in chromosome 21, the regulator gene coding the production of repressor of sensitivity to interferon is in chromosome 16.

Cells, Cultured↗

[Action of interferons on the reproduction of herpes simplex viruses in in vitro experiments].

Tests of various interferon preparations (alpha, alpha2, alpha-beta, beta, and swine leukocyte) in human diploid fibroblast culture for the presence or absence of cytopathic effect of herpes simplex viruses type 1 and 2 (HSV-1 and HSV-2) demonstrated antiviral effect of all interferons with the exception of lymphoblastoid one. Preparations of alpha and swine leukocyte interferons were the most effective for inhibition of HSV-1 reproduction. Recombinant interferon was 10-fold and fibroblast interferon 100-fold less active for HSV-1 than alpha- and swine leukocyte interferons. All the interferons under study (alpha-beta) were similarly active in their antiviral effect on HSV-2 reproduction.

Animals↗

[Differences in the properties of the interferons produced by the leukocytes of healthy persons and of cancer and leukemia patients].

In vitro production of interferon by blood leukocytes from patients with lymphosarcoma, lymphogranulomatosis, leukemia, cancer tumours, pneumonia, as well as by leukocytes of mice with Rauscher leukemia, and mice in the condition of hyporeactivity to interferon inducer was studied. Alongside with quantitative differences in interferon production, biological differences in the properties of interferons produced of normal and sick humans and animals were revealed. The biological differences consist in that the interferon produced by leukocytes from cancer and leukemia patients interacting with homologous cell culture is conducive to more rapid formation of resistance to the indicator virus than the interferon produced by normal leukocytes. Thus, resistance of the homologous cell culture to the infection with the indicator vesicular stomatitis virus developed within 1--2 hours after contact with leukocyte interferon from patients and only within 5--6 hours after contact with that of normal subjects. This finding is not specific for cancer and leukemia, as the same was observed with specimens from patients with pneumonia and from mice hyporeactive to interferon inducer. It is suggested that patients with cancer and leukemia have a state of interferon hyporeactivity.

Adolescent↗