[A granulopoiesis inhibitor. Synthesis and biological activity]. / Ingibitor granulopoéza. Sintez i biologicheskaia aktivnost'.

Three schemes of synthesis for pentapeptide Glp-Glu-Asp-Cys-Lys-OH were compared was carried out. Acetamidomethyl protection was used for the mercapto group of cysteine. For the same purpose, cystine was used as the starting compound for synthesis. The optimal method was shown to be the solid phase method with S-acetamidomethyl cysteine protection that can be removed by mercuric acetate before the cleavage of a peptide from a polymer. The stabilized peptide inhibits proliferation of bone marrow cells of patients with chronic myeloleukemia 5- to 20-fold and has a less pronounced effect (up to 2-fold inhibition) on peripheral blood cells. Thus, its application for the therapy of hemoblastoses is promising.

[Molecular cloning of cDNA encoding human prointerleukin-6]. / Molekuliarnoe klonirovanie kDNK, kodiruiushchei prointerleikin-6 cheloveka.

The data are presented on the cloning and sequencing of cDNA coding for human interleukin-6. The variability of cDNA proIL-6 cloned from different cellular sources was studied. The variability of cDNA proIL-6 may be expressed as heterogeneity of 5'- and 3'-end sequences of cDNA as well as single base-pair changes.

[An interleukin-1 beta efficacy study in the treatment of combined radiation-thermal lesions]. / Issledovanie éffektivnosti interleikina-1 beta pri lechenii kombinirovannykh radiatsionno-termicheskikh porazhenii.

The experiments were carried out on F1 (CBA x C57B16) male-mice. It was shown that, in contrast to a therapeutic effect of IL-1 for the solely irradiated mice, a single subcutaneous injection of 100 micrograms/kg recombinant human IL-1 beta in 4 h after a combined radiation-thermal injury (CRTI) increased significantly the death rate of the animals within the first 2-4 days. Administration of 150 ng IL-1 per mouse in 4, 24, or 48 h after the CRTI decreased an average life-span of mice. A single injection of cytokine in 5 days after the CRTI increased the survival rate by 45%. Repeated injections IL-1 with a dose of 100 pg per mouse in 2, 4, and 6 days after the CRTI did not aid in the haematological indices and did not affect the survival rate of the animals.

[Cell population kinetics in the mouse epidermis stimulated by plucking the hair]. / Kinetika kletochnykh populiatsii v épidermise myshei, stimulirovannom vyshchipyvaniem volos.

Indices of mitotically dividing and DNA-synthesizing cells, the curve of labeled mitoses, and the continuous 3H-thymidine labeling were used for analysing the kinetics of epidermis cell populations in mice C57Bl after plucking. Within the initial 15 hours following stimulation, only one cell population was seen to start proliferating. This passed through the period of transformation (6 hours) and G1-period (3 hours) to enter into S-phase 9 hours after plucking. At this time, the increase in the mitotic level occurs, being at the expense of part of the cells leaving R2-phase. 20 hours after the operation, the cycle of the first population is over, in part of these cells, after having left S-phase, remain in R2-phase. At the same time, epidermocytes of another population are seen to commence their entry into S-phase. Determined from the curve of labeled mitoses, the duration of the whole cycle of epidermocytes, and of G1, S, and G2+M phases appeared to be 12, 3, 6 and 3 hours, respectively.

[Effect of epidermal chalones on cell proliferation in regenerating epidermis]. / Vliianie épidermal'nykh keilonov na proliferatsiiu kletok regeneriruiushchego épidermisa.

The data on the kinetic analysis of epidermocyte proliferation after hair plucking earlier reported elsewhere (Ketlinsky 1980), were used for studying the epidermal chalone action on the interfollicular epidermis regeneration. In two series of experiments, G1-S inhibitory effect of epidermal chalones has been studied. Chalones were injected in various periods of time after plucking, and their effect was registered within 15 hours. The inhibitory effect of chalones was shown to occur, if they were injected at the first six hours after plucking. Chalones injection 15 hours after operation, when the second epidermocyte population had entered into proliferation, preserved the development of epidermis hyperplasis. The highest inhibitory action of chalones on epidermocyte proliferation occurred, if they were injected just before the operation. In this case, the induction of proliferation was not revealed for up to 25 hours after plucking. It is proposed that chalones may play an important role in the non-specific resistance of the cell.

[Use of immunochemical methods for characterization and purification of tissue-specific inhibitors of mitotic activity (chalones)]. / Ispol'zovanie immunokhimicheskikh metod dlia kharakteristiki i ochistki tranespetsificheskikh ingibitorov mitoticheskoi aktivnosti (keilonov)

The 81% ethanol-precipitable fraction of water-soluble proteins from skin inhibiting the proliferation of epidermal tissues was shown to contain 9 protein components according to acrylamide gel disk-electrophoresis. Seven of these were identical to homologous serum proteins and could be adsorbed on the corresponding immunosorbents. Two proteins remained in the solution after immunoadsorption. Their electrophoretic properties were the same as those in the total 81% ethanol fractions. These proteins like the 81% ethanol fraction inhibited the entering of cells into mitosis and DNA synthesis phase.

[Determination of "functional units" of rat epidermis during its histogenesis]. / Stanovlenie "funktsional'nykh edinits" épidermisa krys v protsesse ego gistogeneza.

Sheets and cryocut sections of embryonic, newborn and aged rats have been analyzed. The epidermis of aged rats was confirmed to consist of "functional units", each of them corresponds to the square of one scale and has a hexagonal shape. In the epidermis of 19, 20, 21 day old rat embryos these structures were not observed 4-5 days after birth single hexagonal cells appeared in the granular layer whose formation completed by day 6. Non-organized cornified cells were substituted by hexagonal scales in 10-12 day old neonatal rats.

[Histidine-rich protein synthesis in the mouse epidermis in the early periods after stimulation of epidermocyte proliferation and the effect of chalones]. / Izuchenie sinteza gistidin-bogatykh belkov v épidermise myshei v rannie sroki posle stimuliatsii proliferatsii épidermotsitov i vliianie na nego keilonov.

Using autoradiographic and biochemical methods, the induction of epidermocyte proliferation in adult rats by plucking was shown to stimulate histidine-rich protein synthesis molecular markers of epidermocyte differentiation 6-8 hours before DNA synthesis. Epidermal chalones stimulate 3H-leucine incorporation into urine-dissolving proteins of the epidermis and diminish histidine-rich protein synthesis. These data suggest that chalones not only inhibit the epidermocyte proliferative activity, but also influence the processes of its differentiation.

[Effect of rat liver chalones on liver cell proliferation at different times after partial hepatectomy]. / Osobennosti vliianiia keilonov pecheni krys na proliferatsiiu kletok pecheni v razlichnye sroki posle chastichnoi gepatéktomii.

The action of rat's liver ethanol extract (72--81 per cent saturation) on cell proliferation of this organ at various periods after a partial hepatectomy has been studied. The most sensitive periods of the action of G1- and G2-chalone were, resp., the time of cell transformation, and the middle of the premitotic period of cell cycle. The action of G2-chalone used is organ-specific, since the drug decreased the mitotic activity of both hepatocytes and stromal cells. At the same time, the proliferation of ear, tongue and small bowel epithelial cells remained unchanged.

[The effect of recombinant human interleukin-1 beta on the repopulation of bone-marrow colony-forming cells in mice subjected to the action of radiation and burns]. / Vliianie rekombinantnogo interlekina-1 beta cheloveka na repopuliatsiiu kostnomozgovykh kolonieobrazuiushchikh kletok u myshei, podvergnutykh deistviiu radiatsii i ozhoga.

The radioprotective and restorative (therapeutic) effects of human recombinant interleukin-1 beta (IL-1 beta) on the population of bone marrow CFU-S of mice, subjected to either sublethal doses of ionising irradiation itself or the same irradiation in combination with thermal burn, are investigated. Both the effects of the agent are registered under both in vitro and in vivo irradiation in semi-, syn- and allogeneic animals. If the irradiation was combined with thermal burn, the "therapeutic" effect of the agent was demonstrated at irradiation dose equal to 3.06 Gy rather than to 6.12 Gy. If the bone marrow cells were irradiated in vitro in dose 3.06 Gy with the following heat shock at 42 degrees C for 10-20 min, the "therapeutic" effect of IL-1 beta was seen only if it was added to cells before rather than after irradiation. The radioprotective effect of IL-1 beta is maintained under in vitro, as well as in vivo conditions in the allogeneic system of transplantation of the CBA donor bone marrow to the C57BL mice.

[Interleukin-1-like factor from human B-lymphocytes transformed by the Epstein-Barr virus]. / Interleikin-1-podobnyi faktor iz B-limfotsitov cheloveka, transformirovannykh virusom Epshteina--Barra.

The NC-37, EBV-transformed human B-lymphoblastoid cell line spontaneously produces interleukin (IL)-1-like factor, which is able to stimulate proliferation of mouse thymocytes and human fibroblasts. The IL-1-like factor production can be enhanced by prodigiozan and by the conditioned medium of human peripheral blood mononuclear cells. The NC-37 cells have a membrane-associated form of IL-1-like factor also. The molecular mass of the intracellular precursor of this factor determined by gel-filtration is 35-40 kDa, and that of the secretory form--18-20 kDa. The secretory form has the following isoelectric points: 4.5; 6.8; 7.2-8.4.

[The effect of recombinant interleukin-1 beta on the chemotactic activity of neutrophilic leukocytes]. / Vliianie rekombinantnogo interleikina-1 beta na khemotaksicheskuiu aktivnost' neitrofil'nykh leikotsitov.

The role of interleukin-1 in the activation of neutrophils, the main effects of inflammatory reaction, is still unclear. This study has demonstrated that the recombinant preparation interleukin-1 beta (IL-1 beta) which the authors have obtained fails to produce a direct action on the locomotor functions of neutrophils. At the same time, injection of IL-1 beta in mice leads to neutrophilic migration to the injection site and their efflux into peripheral blood. These findings confirm the assumption that interleukin-1 produces a mediator effect on neutrophilic chemotaxis.

[The biological activity of human recombinant interleukin-1 beta when administered in vivo]. / Izuchenie biologicheskoi aktivnosti rekombinantnogo interleikina-1 beta cheloveka pri vvedenii in vivo.

Human recombinant IL-1 beta injected intraperitoneally into CBA mice dose-dependently induced leukocytosis, stimulated phagocytosis and reduced tetrazolium nitroblue by peritoneal leukocytes, colony formation by bone marrow cells, enhanced Con A and IL-2-induced proliferation and IL-2 production in thymocytes and splenocytes. Recombinant IL-1 beta restored bone marrow cell proliferation reduced after 5-fluorouracil treatment and significantly increased the survival rates of lethally irradiated mice.

[Structural and functional analysis of the human immunodeficiency glycoprotein gp120 with homologous synthetic peptides]. / Strukturno-funktsional'nyi analiz glikoproteina gp120 virusa immunodefitsita cheloveka s pomoshch'iu sinteticheskikh peptidov, gomologichnykh ego strukture.

The purpose of the study was to identify sites of gp 120, which are responsible for CD4 binding and induce tumor necrosis factor-alpha (TNF-alpha) synthesis. Seven peptides were synthesized from gp 120. The peptides were studied in the following biological tests: binding to CD4 molecules of the Jurkat cell clones 3G6 and PBMC of healthy persons. There was TNF-alpha induction in healthy and HIV-positive individuals and its correlation was found with p24 antigenemia in HIV patients. The peptides 420-440, 426-452, 369-384, 255-272 bind to T-lymphocytic CD4 and induced TNF-alpha. The peptide 436-451 binds to CD4, but failed to induced TNF-alpha, which suggests that the latter may be used as a basis for HIV-infection vaccine.

[Tumor necrosis factor-alpha and interleukin-1beta in the blood plasma of patients with HIV infection]. / Faktor nekroza opukholi-alpha i interleikin-1beta v plazme krovi bol'nykh VICh-infektsiei.

The paper presents examination findings of 67 HIV-infected patients: 32 children aged 2.5 to 16 years and 35 adults aged 21 to 46 years. The proportion of patients with higher alpha-tumor necrosis factor and interleukin-1 beta increased with progression of the disease, the two parameters being higher in the children than in the adults. A correlation was found between the appearance of cytokines in the plasma and some clinical signs, such as fever, weight loss, anemia, neurological disorders. A parallel study of the patients' immunograms indicated significant correlations between the degree of impairments in the composition of lymphocyte subpopulations and the appearance of plasma cytokines.

[Dynamics of skin cell proliferation and differentiation and the development of epidermocyte reactivity in the process of histogenesis: the problem of chalones]. / Dinamika proliferatsii i differentsirovki kletok kozhi i stanovlenie reaktivnosti épidermotsitov v protsesse gistogeneza: k probleme keilonov.

The dynamics of proliferative activity in the epidermis and dermis cells, as well as some morpho-functional indices in the skin epithelium have been studied in 17-21 days old embryos and 1, 3, 5, 8, 10 and 20 days old rats. The epidermis acquired its definitive properties by the 8th day of postnatal development whereas the skin as an organ formed by the 20th day. The epidermocytes of the developing skin responded to the damage by a distinct proliferative reaction from the 8th day on. The epidermal chalones isolated from the skin of adult animals inhibited the division of epidermocytes in 8, 10 and 20 days old animals. No effect was observed upon the injection of epidermal chalones into 1, 3 and 5 days old rats.

[Tissue-specific regulation of proliferative processes in the tissues normally and in pathology: on the problem of chalones]. / Tkanespetsificheskaia reguliatsiia proliferativnykh protsessov v tkaniakh v norme i pri patologii: k probleme keilonov.

The paper discusses the author's own and literary data on the role of chalones (tissue-specific inhibitors of proliferative processes) in the maintenance of tissue homeostasis normally and pathologically. It is suggested that chalones be used both as regulators of cell multiplication and as markers of histogenesis.

[Histoautoradiographic and biochemical study of the transport of atherogenic lipoproteins in the vascular wall]. / Gistoavtoradiograficheskoe i biokhimicheskoe issledovanie transporta aterogennykh lipoproteidov v sosudistuiu stenku

Transport of serous pre-beta and beta-lipopropeins (beta-LP) labeled by C14 protein and by C14 lipid into the wall of the aorta was studied histoautoradiographically and biochemically. The aortas of healthy rabbits and rabbits wuth experimental atherosclerosis were perfused in vitro with a medium containing rabbit pre-beta and beta-LP during 6 hours. After perfusion the mark was identified histoautoradiographically in all layers of the aorta. The presence of gradient in distribution of the mark from the inner layers of the aortas towards the outward part of the media indicated that the process of infiltration of the wall of the LP vessel was caused by their penetration from the lumen of the aorta. Nonuniformity in distribution of LP penetrated into the atherosclerotic aorta was noted, which was considered in connection with the changes occurred in the connective tissue of the wall of the aorta in the process of atherogenesis. Results of both morphological and biochemical investigations confirm an increased permeability of the aorta wall for LP in atherosclerosis and also substantiate the assumption about penetration of pre-beta and beta-LP into the wall of the vessel as a whole particle.

[Effect of chalone-containing aorta extracts on regression in experimental atherosclerosis]. / Vliianie keilonsoderzhashchikh ékstraktov aorty na regressiiu éksperimental'nogo ateroskleroza.

The effect of chalone-containing aortic extracts on proliferative activity of smooth muscle cells was examined in conditions of experimental hypercholesterolemia. The tissue-specific cell proliferation inhibitor present in the extract is shown to depress mitotic activity of smooth muscle cells in postnatal rats. The area under aortic atherosclerotic lesion diminished twofold as compared to that of the controls. Morphologically, atherosclerotic changes are seen as lipid plaques.

[Dynamics of the proliferative activity of aortic cells in the process of the formation of an atherosclerotic plaque]. / Izuchenie dinamiki proliferativnoi aktivnosti kletok aorty v protsesse obrazovaniia ateroskleroticheskoi bliashki.

It was demonstrated by 3H-thymidine histoautoradiography that after 3 weeks of a cholesterol diet the number of labelled endothelial and subendothelial cells in the aorta of rabbits increases sharply. With the gradual development of experimental atherosclerosis (after 6 weeks of the experiment) two types of atherosclerotic patches are found in the aorta, which differe one from the other in the degree of "maturation" and the character of distribution of the proliferating cells. Experiments with "setting apart" of the 3H-thymidine label show clearly the possibility of transformation of the subendothelial cells into lipid macrophages. The main growth of the cell mass of the atherosclerotic patch, however, occurs because the lipid macrophages themselves proliferate. The hypothesis claiming that the subendothelial cells are the precursors of all cell elements forming the patch is discussed.