[The preclinical assessment of the activity and pharmacological action of native human interleukin-2]. / Predklinicheskaia otsenka aktivnosti i farmakologicheskogo deistviia nativnogo interleikina-2 cheloveka.

It was demonstrated in in vivo and in vitro experiments that interleukin-2, obtained by cultivation of donor lymphocytes and purified by gel filtration, induces the production of mouse and human killer lymphocytes possessing high cytolytic activity against tumor cells. Interleukin-2 does not cause irreversible changes of the physiological and morphologic indices of vital activity in mice.

[Effect of the carcinogenic metabolites of aromatic amino acids on oxidative processes in lipids in vitro and in vivo]. / Vliianie kantserogennykh metabolitov aromaticheskikh aminokislot na okislitel'nye protsessy v lipidakh in vitro i in vivo.

A comparative study of the effect produced by endogenous carcinogens (p-hydroxyphenyllactic and 5-methoxyindole-3-acetic acids) and their non-cancerogenic analogues on lipid peroxidation in vitro and in vivo was performed. It has been found that cancerogenic tyrosine and serotonin metabolites, unlike their non-cancerogenic analogues, increase lipid peroxidation in vitro. In vivo, cancerogenic tyrosine metabolite--p-hydroxyphenyllactic acid--is capable both of increasing and decreasing antioxidative lipid activity in the animal liver.

[Effect of the carcinogenic tyrosine metabolite p-hydroxyphenyllactic acid on the ascorbic acid concentration in the organs and blood of mice]. / Vliianie kantserogennogo metabolita tirozina p-oksifenilmolochnoi kisloty na kontsentratsiiu askorbinovoi kisloty v organakh i krovi myshei.

The effect of cancerogenic tyrosine metabolite, p-hydroxyphenyllactic acid, on the concentration of ascorbic acid in the organs and blood of mice has been studied. p-Hydroxyphenyllactic acid was demonstrated to decrease considerably ascorbic acid concentration in the liver, adrenal glands and blood of mice. The above phenomenon and the previous data on tyrosine aminotransferase induction by p-hydroxyphenyllactic acid suggest the existence of two interdependent mechanisms of cancerogenic tyrosine metabolite (p-hydroxyphenyllactic acid) accumulation.

[Transplacental carcinogenic effect of the serotonin derivative 5-methoxyindoleacetic acid]. / Transplatsentarnoe kantserogennoe vozdeistvie proizvodnogo serotonina 5-metoksiindolil-3-uksusnoi kisloty.

Transplacental administration of serotonin metabolite 5-methoxyindole-3-acetic acid possessing blastomogenic activity induced the development of malignant and benign neoplasms (lymphosarcomas, adenomas, hepatomas and other tumours) in 84% of C57BL/6 mouse progeny. The number of neoplasms was significantly higher, than in the control, they appeared earlier and were more malignant.

[Blastomogenic activity of biogenic methoxyindoles]. / Blastomogennaia aktivnost' biogennykh metoksiindolov.

A considerable blastogenic activity of biogenic methoxyindoles--melatonin, 5-methoxytryptamine (5-MOT) and their common metabolite--5-methoxyindolyl-3-acetic acid (5-MIAA) was established by prolonged s.c. injection in C57BL/6 mice. However, the blastogenic effect of 5-MOT decreased by 26% when its further metabolism to 5-MIAA was blocked for some time and the synthesis of its carcinogenic metabolite was inhibited. These results showed that the blastogenic effect of 5-MOT is not direct; and it is mediated by its transformation to 5-MIAA in the body.

[Carcinogenic action of 5-methoxytryptamine related to its transformation into 5-methoxyindolyl-3-acetic acid]. / Kantserogennoe deistvie 5-metoksitriptamina, sviazannoe s ego prevrashcheniem v 5-metoksiindolil-3-uksusnuiu kisloty.

A considerable blastomogenic effect of metabolite serotonin 5-methoxytryptamine (5-MOT) subcutaneously administered for a long time to C57BL/6 mice was established. This effect was decreased noticeably if the further metabolism of 5-MOT into 5-methoxyindolyl-3-acetic acid (5-MIAA) was blocked by pyrazidol. These results explain the fact that the blastomogenic effect of 5-MOT is not direct but is caused by the transformation of 5-MOT into its final carcinogenic metabolite 5-MIAA.

[Morphological and cytochemical characteristics of spontaneous hemoblastoses in AKR mice]. / Morfologicheskaia i tsitokhimicheskaia kharakteristika spontannykh gemoblastozov myshei linii AKR.

Spontaneous hemoblastoses of AKR mice are widely used in experimental oncology and hematology. To study their morphological characteristics, 500 AKR mice were used. Of these, 400 animals were followed up throughout their lives. Ten animals were sacrificed monthly out of the group of 100 rats. All the animals which died or were sacrificed were autopsied and subjected to cytological and histological studies. Besides, 36 animals with hemoblastoses were examined cytochemically for the activity of acid and alkaline phosphatases, peroxidase and nonspecific esterase and glycogen. Analysis of the data obtained suggests that hemoblastoses of AKR mice are the generalized forms of lymphosarcoma, characterized by a significant degree of cytochemical and cytological heterogeneity.

[Lectin-dependent cytotoxicity of human peripheral blood lymphocytes]. / Lektinzavisimaia tsitologicheskaia aktivnost' limfotsitov perifericheskoi krovi cheloveka.

The evaluative technique of lymphocyte cytolytic activity in human peripheral blood has been designed. The target cells, lectin (Con A) concentration and incubation time for measuring cytolytic activity of lymphocytes pre-purified from adherent cells have been selected. The mean values of lectin-dependent cytotoxicity in peripheral blood of 50 healthy donors are presented.

[Characteristics of the secretory apparatus of memory T-cells]. / Kharakteristika sekretornogo apparata T-kletok pamiati.

It has been shown that by day 7--8 of cultivation, large lymphocytes and lymphoblasts disappear, the DNA synthesis and cytolytic activity decrease in lymphocyte suspension enriched with a fraction of lymphoblasts obtained on the 5th day of mixed lymphocyte culture. The cytoplasm of medium-size and small lymphocytes adsorbed on the surface of target-cells manifests no signs of secretion: there are no tubular structures or rough reticulum, the Golgi complex is underdeveloped. It is suggested that there is a relationship between the secretory apparatus and cytolytic activity of T-killers.

[Effect of L-ascorbic and D-isoascorbic acids on induced formation of tyrosine aminotransferase in rat liver]. / Vliianie L-askorbinoovoi i D-izoaskorbinovoi kislot na indutsirovannoe obrazovanie tirozin-aminotransferazy v pecheni krys.

Administration of ascorbic acid at moderate doses/0.05-0.1 g per kg of body mass/was shown to induce tyrosine transaminase in liver tissue of intact rats. The enzyme induction depended on the state of adrenal glands and was inhibited by actinomycin D. As distinct from the native form of L-ascorbic acid moderate doses of D-isoascorbic acid did not induce the enzyme in rat liver tissue; these data suggest the relative biological inactivity of D-isoascorbic acid.

[Ultrastructure of the conjugates of cytolytic T-lymphocytes and target cells]. / Ul'trastruktura kon'iugatov tsitoliticheskikh T-limfotsitov i kletok-mishenei.

Conjugates of target cells and of cytological T-lymphocytes obtained on the 11th day after alloimmunization were investigated. The conjugates formed small and medium lymphocytes; mature secretory granules, crystal-like structures and lipids were revealed in their cytoplasm. The lymphocyte is spherical, the area of contact with the target cell does not exceed 5 to 15%. Cytolysis of target cells is observed after 30 to 60 minutes of incubation. The lymphocyte becomes flattened, its nucleus acquires an oval form, and the area of contact with the target cell increases considerably. At the same time hypertrophy and change of orientation of Golgi's complex to the area of contact with the target cell, coalescence of the secretory granules with lipids and crystal-like structures, the appearance of immature secretory granules and vacuolar degeneration of mitochondria are demonstrated. The lymphocyte membrane becomes "desquamated"; structures connected with it, named "membranosomes" are described. It is suggested that the secretory processes in the cytoplasm of cytolytic T-lymphocytes are activated in their interaction with target cells.

[Biosynthesis of pyridoxal-5'-phosphate in lymphocytes stimulated by alloantigens in vitro]. / Biosintez piridoksal'-5'-fosfata v limfotsitakh, stimulirovannykh alloantigenami in vitro.

Dynamics of alterations in pyridoxal kinase activity (key enzyme in biosynthesis of pyridoxal-5'-phosphate) was studied in lymphocytes of mice BALB/c, stimulated by irradiated cells from spleen of mice C3H in vitro. The cytolytic activity of lymphocytes was estimated by amount of Na251CrO4 realised from lysed cell-targets into medium. Maintenance of animals on a diet without pyridoxine within 1-3 weeks did not affect on the capacity of lymphocytes to proliferative in vitro and on their cytolytic activity. At the same time pyridoxal kinase activity was increased 2.5-3-fold in stimulated lymphocytes in presence of pyridoxal. Km value was 2.5-5.0.10(-5) M of pyridoxal for preparations of pyridoxal kinase from lymphocytes either with normal or with increased enzymatic activity. Lymphocytes of mice, kept on the diet without pyridoxine within 5-6 weeks, were characterized by distinctly decreased proliferative and cytolytic activities. Pyridoxal-5'-phosphate, added to incubation mixture in vitro, as distinct from pyridoxal, restored partially the impaired functions of T-lymphocytes.