Publications by authors named "Tiazhelova V"

The data of recent years on apoptosis were revisited to demonstrate that the functioning of signaling proteins during apoptosis depends on their localization on mitochondria or in the cytosol. The major effect of signaling proteins depends on the number of pro- and antiapoptotic domains in their structure, which is observed after cleavage, oligomerization, and complexing with other proteins. The structure of known signaling proteins was analyzed.

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Mathematical modelling used in analysing the postirradiation changes in megakaryocytopoiesis permitted to determine the level of radiation-induced injury in each experiment conducted and to show that megakaryocytopoiesis regulation followed the same mechanism after irradiation as it does normally and after the effect of hydroxyurea and anti-thrombocyte serum. The analysis has demonstrated that after the stem cell death induced by ionizing radiation, the regeneration can be provided by the committed cells, and the level of regeneration is determined by the maturity of precursors.

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Using the developed method of modelling the curves of the fraction of labelled indexes (FLI) in the small intestine epithelium, a relationship was found between the FLI shape and duration of the S phase and the whole generation cycle for various generations of proliferating crypt cells. On the basis of the comparison between the theoretical and experimental FLI the normal values of the generation cycles along the crypt were specified for various intestinal parts. FLI were shaped along the crypt at various time intervals after irradiation.

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Distribution of CFU-S upon daily chronic irradiation of mice with doses of 0.25 and 0.5 Gy during 3-4 months was close to normal: the percentage of individuals without CFU-S capable of forming macrocolonies being high in both cases.

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The role of cells capable of formation of megakaryocytic colonies (CFUm) in regulation of thrombocytopoiesis was studied using a simulation model of megakaryocytopoiesis. The CFUm were shown to be the least differentiated cells involved in regulation of megakaryocytopoiesis in mice upon immune thrombocytopenia and after intravenous injection of hydroxyurea. A correlation was found between the CFUm population productivity and the number of cells in a transit population of the megakaryocytic line which makes it possible to reproduce experimental kinetics in the model.

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Analysis of the earlier obtained data on the effect of hydroxyurea on megakaryocytopoiesis by a simulation model has shown that differentiation of proliferating precursors of the megakaryocytes depends on their amount in bone marrow; the time of their involvement in the proliferating pool increases if the number of proliferating cells decreases. Within 24 h after the treatment with hydroxyurea (900 mg/kg), the transit time for the mouse megakaryocytes is reduced by about 14 h due to acceleration of the latest developmental stages. A hypothesis is put forward which accounts for correlation between the duration of proliferative period and the volume and maturation time of megakaryocytes.

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The cells giving rise to colonies in the spleen of a lethally irradiated recipient after their transplantation (exogenous CFUs) have a higher self-maintaining ability than those that repopulate their own hemopoietic territory after irradiation, due to the migration of these cells from screened territories (endogenous CFUs). The number of exogenous CFUs and their self-maintaining ability do not change with animals ageing.

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A model is proposed to describe the interaction between the erythroid and myeloid haemopoietic compartments their total proliferating potential being limited and the myelopoiesis inhibited in favour of erythropoiesis. With the consecutive diminution of the bone marrow proliferating potential the model describes: (1) the delay in the recovery processes, (2) the fluctuation regime for all the cell strains under study, (3) and the complete inhibition of myelopoiesis.

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From the comparison of the results of model and experimental kinetics of thrombocytopoiesis the following parameters have been quantitatively estimated: (1) the percentage of cells killed during the interphase (interphase death) and (2) the duration of the mitosis delay and the abortive rise. There was a 1.3-1.

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A mathematical model of thrombocytopoiesis is proposed which accounts for the recent data on its regulation. It is shown that the compensatory response of the system to a decrease in the level of thrombocytes in the blood is controlled by the total amount of thrombocytes and megakaryocytes. The proliferation intensity of megakaryocytes and the total number of thrombocytes reveal, respectively, a lineary and a logarithmical dependence on the total number of thrombocytes and megakaryocytes.

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Based on literature data, the main kinds of thrombocytopoiesis regulation are analyzed. It is shown that humoral factors regulate the intensity of proliferation of committed precursors and the mean sizes of mature megakaryocytes. The activity of these factors depends on the numbers of thrombocytes in blood and of megakaryocytes in bone marrow.

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On the basis of the data reported in the literature a model is proposed describing the kinetics of the post-irradiation recovery of the main spermatogenous epithelium populations. In studying the spermatogenous epithelium structure of rodents and comparing the experimental and theoretical curves the parameters necessary for the kinetics estimations have been quantitated and their specific variations analysed. From these the parameters have been obtained and the kinetic curves shaped with a reference to human spermatogenous epithelium.

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