[Effect of mitogenic stimulation and heat shock on protein syntheses in human T cells]. / Vliianie mitogennoi stimuliatsii i teplovogo shoka na belkovye sintezy v T-kletkakh cheloveka.

Effects of moderate (42 degrees C, 1 hour) and strong (44 degrees C, 1 hour) heat shocks on resting (TR) and phytohemagglutinin stimulated human T-cells (TP) were studied. Both treatments were shown to cause in the latter considerable fall of the level of protein synthesis, as compared to resting cells. Mitogen-stimulated cells stopped their proliferation irreversibly and part of them (approx: 40%) died after even mild shock (at 42 degrees C). Following heat treatment in both the cell types the synthesis of heat shock 70 and 90 kDa proteins was induced which was much more pronounced in TR. These and earlier results of the authors allow a conclusion that involvement of cells in active proliferation may decrease their resistance to stress, and that this phenomenon coincides with the diminishing in synthesis and accumulation of stress proteins.

[Study of the characteristics of various hematologic diseases using monoclonal antibodies LT1, LT2 and LT7]. / Kharakteristika nekotorykh gematologicheskikh zabolevanii s pomoshch'iu monoklonal'nykh antitel LT-1, LT-2, LT-7.

Monoclonal antibodies (MCA) LT1, LT2 and LT7 were characterized. It was established that MCA LT1 and LT2 (IgG1 and IgM classes, respectively) interacted with antigen 67 kD, and MCA LT7 (IgGZa)--with antigen 40 kD. MCA LT1, LT2 and LT7 were shown to identify normal and neoplastic cells of T-lymphoid type. MCA LT1 and LT2 also reacted with B-lymphocytes of chronic lymphocytic leukemic patients. MCA LT1 and LT2 were referred to CD5 (Cluster of Differentiation) and MCA LT7--to CD7 by the molecular weight of an identified antigen and the spectrum of its expression. The importance of MCA studied in the diagnosis of subtypes of acute and chronic lymphocytic leukemia has been confirmed.

[Effect of the tumor promoter TPA on the distribution of PHA-stimulated human lymphocytes by cell cycle phases]. / Vliianie opukholevogo promotora TFA na raspredelenie stimulirovannykh FGA limfotsitov chelovkea po fazam keltochnogo tsikla.

Patterns of the cell cycle distribution in human peripheral blood lymphocytes, stimulated by PHA alone and PHA plus 12-o-tetradecanoylphorbol-13-acetate (TPA), were studied using DNA cytometry in different times after PHA stimulation. In the first period (nearly 3 days after PHA stimulation) TPA induces no significant differences in the characters under consideration, but in the later period, when the proliferation of the cultures stimulated by PHA alone is reducing, in other cultures stimulated by PHA plus TPA the percentage of cells in S-phase does not reduce, whereas the percentage of cells in G2-phase is rising, which may suggest that this phase is blocked. Concurrently the tetraploid cells are appearing. Accumulation of cells in G2-phase can be overcome by the application of chlorpromazine, which is known to inhibit the membrane-associated protein kinase C.

[Induction of the traits of the differentiated T-cell phenotype in the blast cells of patients with acute lymphoblastic leukemia. I. The expression of T-cell markers as affected by different inducers]. / Induktsiia nekotorykh priznakov differentsirovannogo T-kletochnogo fenotipa u blastnykh kletok bol'nykh ostrym limfoblastnym leikozom. I. Ekspressiia T-kletochnykh markerov pod vliianiem razlichnykh induktorov.

The expression of T-lymphocyte markers has been demonstrated by blast cells of patients with non-T, non-B and pre-T-cell acute lymphoblastic leukaemia (ALL). The main inducing agent is phytohemagglutinin (PHA). Its action was enhanced when combined with phorbol ether (TPA) or ouabain. Dimethylsulfoxide, ouabain and concanavalin A had no similar inducing effect. TPA caused the expression of some T-cell markers revealed by monoclonal antibodies but had only a little inducing effect to E-receptor.

[Induction of the traits of the T-cell differentiated phenotype in a blast cell population from patients with acute lymphoblastic leukemia. II. Parallel changes in the antigenic characteristics and functional properties of blast cells as affected by inducers]. / Induktsiia nekotorykh priznakov differentsirovannogo T-kletochnogo fenotipa v populiatsii blastnykh kletok bol'nykh ostrym limfoblastnym leikozom. II. Parallel'nye izmeneniia antigennykh kharakteristik i nekotorykh funktsional'nykh svoistv blastnykh kletok pod vliianiem induktorov.

Data are provided which allow to assume that the appearance of T-cell markers on blast cells of patients with non T-, non B- and pre-T-cell acute lymphoblastic leukaemia may reflect the process of differentiation in leukaemic lymphoblasts in T-cells under the action of phytohaemagglutinin (PHA) combined with phorbol ether (TPA) or ouabain. As result of the induction, in the lymphoblast population the number of cells carrying the markers of non-differentiated phenotype decreased, which was proportional to the increase in the number of cells with differentiated T-lymphocytic phenotype. The expression of T-cell markers was suppressed by the inhibitors of transcription and protein synthesis. As a result of induction the leukaemic cells acquire the ability to form T-cell colonies in semisolid agar which reflects their functional changes under the action of inducers. Possible mechanisms of PHA inducing action are discussed.

[Changes in the content of potassium, sodium and potassium influx in human peripheral blood lymphocytes during long-term cultivation with phytohemagglutinin]. / Izmenenie soderzhaniia kaliia, natriia i vkhodnykh potokov kaliia v limfotsitakh perifericheskoi krovi cheloveka pri dlitel'nom kul'tivirovaniia s fitogemaggliutininom.

Intracellular potassium, sodium and potassium influx were examined in PHA-activated human lymphocytes within 6 days of cultivation. DNA flow cytometry was used to estimate the percentage of cells in G1, S and G2 + M phases. Potassium influx and content per g protein were found to be increased, whereas sodium content decreased with the progression of cells from G1 to S phases, being maximum on the 3rd day. Later on the percentage of cells in S phase was seen diminished, and the potassium content decreased just as sodium content increased. It is concluded that ionic changes may correlate with the entering of cells into S phase.

[Possible mechanisms regulating the entry of normal and neoplastic cells into the DNA synthesis phase]. / Vozmozhnye mekhanizmy reguliatsii vstupleniia normal'nykh i neoplasticheskikh kletok v fazu sinteza DNK.

Literature data concerning some aspects in the regulation of the entry of normal and neoplastic cells into the phase of DNA synthesis are reviewed. Basing on the analysis of data reported by different authors, a hypothetical model is suggested for regulation of cell passing from G- to S-period. The main chain in the regulation is the constitutive synthesis of protein-repressor which blocks the expression of genes whose products are necessary for replication ("replication genes"). The repressor inactivation is achieved by growth factors through protein kinases. A comparison is made between the transcriptional mechanisms in eukaryotic and prokaryotic cells. Four hypothetic types of genes have been isolated responsible for regulation of progression of the cell to phase S. The role of quantitative and/or qualitative changes in the products of these genes in neoplastic transformation is discussed.

[Initial changes in ouabain-dependent and ouabain-resistant potassium fluxes in human peripheral blood lymphocytes exposed to phytohemagglutinin]. / Nachal'nye izmeneniia uabainzavisimykh i uabainrezistentnykh potokov kaliia u limfotsitov perifericheskoi krovi cheloveka pri deistvii fitogemaggliutinina.

The early changes in potassium fluxes in PHA-treated human lymphocytes were studied. The increase in both ouabain-sensitive potassium influx and ouabain-resistant potassium efflux at the optimal mitogenic concentration of PHA was observed. No change in potassium content was found.

[Effect of interleukin 2 on blast proliferative activity and expression of T-cell markers in patients with acute lymphoblastic leukemia]. / Vliianie interleikina-a na proliferativnuiu aktivnost' blastov i ékspressiiu nekotorykh T-kletochnykh markerov u bol'nykh ostrym limfoblastnym leikozom.

The proliferative activity of blast cells from patients with acute lymphoblastic leukemia was compared with the activity of lymphoid cells of the thymus and blood of healthy subjects. The spontaneous proliferative activity in cells obtained extempore varied widely. On the basis of this index groups of patients with high proliferative activity (group 1) exceeding the level of thymocyte proliferation and with low proliferative activity (group 2) were distinguished. Direct correlation was revealed between the initial spontaneous proliferative activity and the number of leukocytes as well as with the absolute number of blasts in the blood. A decrease in the initial high proliferative activity in the time course of cultivation was noted in some patients of group 1 (group 1B). In the majority of these patients (91%) the administration of interleukin-2 into the cultural medium prevented a decrease in the proliferative activity. In the other patients of group 1 (group 1A) a high spontaneous proliferative activity was not decreased during cultivation. In group 1A a proliferative response to T-cell growth factor was observed in 36% of patients. The patients' blast cells in group 2 did not respond to this lymphokine. The expression de novo of T-cell markers was observed in some patients of group 1 as a result of interleukin-2 action. The role of interleukin-2 in the pathogenesis of acute lymphoblastic leukemia is discussed.