Below were demonstrated the differences in the cell reaction of the chromosome loci transference induced by adaptive doses X-radiation in the cells nucleus in norm cells and in cells with repair process defect of the oncological patients and patients with hereditary disease. It was supposed that the transference of the homologous chromosome loci is necessary for the realization of the correct DNA's double strand repair. The chromosome loci transference in normal cells could be induced by different factors such as X-radiation, RNA-polymerize II repression by alpha-amanitin and possible by other factors. In cells with BSCA1 and BRCA2 genes mutations the chromosome loci transference could not be induced by the X-radiation, but it could be induced by the RNA-polymerize II repression by alpha-amanitin. The defect of the chromosome loci transference condition on genetics or the another determinatives and this defect could be the one of the important reasons of the genome instability. There was suggested the new conception of the mechanisms of the cell differentiation and cell chronological senescence. The vector of the cell differentiation mechanisms is the progressive chromatin condensation determined by the physical mechanisms, i.e., transformation from less probable (the stem cells) to more probable cell system state (the differentiated cells) and as a result of it changing of the genes transcription. The continued chromatin condensation (most pronounced in the old cells) decreases the probability of the realization of the DNA repair as the reason of the chromosome loci transference limitation. In this work are presented experimental and theoretical information that proves our conception.

A review of the data obtained by the author and his collaborators in studying tissue specific esterase of Drosophila males. Patterns were established for molecular-genetic regulation of synthesis of this isozyme.

The author develops previously expressed hypothesis of causative relationship between primary hypertension and altered mitochondrial energy production, reduced ATP synthesis and tissue energy deficit. These deviations in energy metabolism originate on the basis of generalized alteration of membrane regulation of intracellular Ca(2+) distribution leading to mitochondrial calcium overload and lowering of ATP synthesis. Critical factor determining mitochondrial calcium overload is the development of functional insufficiency of mPT pores of inner mitochondrial membrane facilitate Ca(2+) outflow from matrix of organelles. Elevation of systemic blood pressure is associated with emergence of energy deficit in brain tissue which stimulate vasomotor centers of brain stem and efferent activity of sympathetic nervous system supplying cardiovascular system. Stationary elevated blood pressure level in long term is supported by structural-functional rearrangement of circulation. Important component of the latter is reduction of capillary net and related centralization of circulation. Blood pressure in the central part of the arterial system is determined by demands of new level of energy metabolism in cells.

We studied the mechanisms of erythropoiesis regulation in a conflict situation and during paradoxical sleep deprivation. Plastic reconstruction of the erythroid hemopoietic stem during experimental neuroses is regulated by a complex multicomponent and multilevel system. This system consists of central adrenergic structures, sympathetic part of the autonomic nervous system, and alpha- and beta-adrenoceptors on erythroid precursors and cells of the hemopoietic microenvironment. Erythroid cells receive instructive information from the central nervous system via adrenoceptors on cells of the hemopoiesis-inducing microenvironment and erythroid precursors. Hyperplasia (conflict situation) and suppression of erythropoiesis (paradoxical sleep deprivation) are associated with specificity of central adrenergic regulatory mechanisms.

Main indices of efficacy such as objective response and stabilization frequency, objective response median and survival rate were evaluated in 84 patients with disseminated breast cancer receiving different doses of cytostatics: high-dose chemotherapy (HDC) plus transplantation of peripheral blood stem cells, standard-dose (SDC), dose reduced by 20% (RDC20) or by 50% (RDC50). There was an inverse correlation between complete+partial response frequency, on the one hand, and dosage, on the other: highest dose--70% and lowest dose--11.1%. Objective response median in both groups was pretty close--8.5 +/- 5.5 and 5 +/- 0.4% months, respectively. The lowering of dose involved a higher risk of tumor progression from 15% after HDC, 46.6%--SDC and 44.4%--RDC20 to 61.1% after RDC50, with likelihood of objective response decreasing. Nether median nor mean survival rates depended on dosage, nor the difference was significant (p = 0.72). Hence, adequate dose proved to be an important factor, as far as treatment efficacy is concerned. Escalation to high dose was followed by an increase in objective response rates to 70%, SDC - 35.7%, RDC20--33.4% and RDC50--11.1%. Yet, nether dose escalation nor dose reduction involved significant variation in survival (p = 0.72).

The qualitative and quantitative composition of the hemopoietic tissue has been studied and the processes of erythropoiesis regeneration in mice treated with cyclophosphamide and skullcap (Scutellaria Baicalensis) extract against a background of cyclophosphamide treatment have been studied. The skullcap extract produced a significant erythropoiesis-stimulating effect under the conditions of cytostatic myclosuppression. Activation of the erythroid branch of hemopoiesis was related to the growing number of erythropoiesis precursor cells in the bone marrow and also to an increase in the concentration of humoral factors of erythropoiesis regulation in the peripheral blood serum.

We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (LD50) on the frequency of dominant lethal mutations and two-strand DNA breaks (TSBs) in germline cells and on an increase in frequency in gene mutations W(y) in pigment cells of first-generation mice. The results indicated that spermatogenesis stages most sensitive to nickel sulfate (at a dose of 1.0 mg/kg) are spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia. No statistically significant increase in the total TSB level was detected in spermatozoids 4 weeks after exposure. At the same time, a significant (P < 0.05) increase in percentage of cells with an extremely high level of DNA fragmentation (supposedly apoptotic cells) was observed upon exposure at a dose of 0.5 mg/kg. Nickel sulfate at doses of 5.0 and 1.0 mg/kg induced a marked increase in the c-kit gene expression in pigment cells of heterozygous first-generation WR mice as compared to control (P < 0.001). It was shown that the nonobservable adverse effect level (NOAEL) of nickel sulfate on the dominant lethal mutation frequency and gene mutations was 1/200 LD50, while the lowest observable adverse effect level (LOAEL) was 1/100 LD50.

The experimental study of macrophage-activating chemotactic peptide N-f-met-leu-phe-gly (chemotaxic peptide), as well as its liposomal form, on the proliferation and migration of colony-forming precursor cells in mice was carried out. The study revealed that the subcutaneous injection of chemotaxic peptide into mice in a dose of 20 Mg led to a pronounced, but short-term increase in the proliferation of such precursor cells in the marrow: as shown by the hydroxyurea "suicide" method, a day after the injection almost 50% of hematopoietic stem cells entered the S-phase of the cellular cycle; in addition, an increase in the content of colony-forming precursor cells in the peripheral blood and the spleen was observed. The injection of chemotaxic peptide, incapsulated into liposomes, led to a considerable increase in the duration of the stimulating effect, manifested by the maintenance of a stable proliferative state of the pool of hematopoietic stem cells during 4 weeks (the term of observation). This effect could be attributed to the formation of the liposomal "depot" and the gradual liberation of chemotaxic peptide from it.

The midgut epithelium of the virgin females in Ixodes ricinus, L. pacificus, and I. persulcatus is represented by the digestive cells of nymphal phase and stem cells. Digestion of feed is performed by the one generation of digestive cells of nymphal phase and two generations of digestive cells of adult females. The generation of secretory cells and two generations of digestive cells are absent. The feeding of virgin females is not completed but interrupted in the second phase during the period of slow feeding and preparation of the intestine for the third phase.

To study correlations between body mass and height of the newborn, Apgar scale estimates, gestation time, volume of the obtained umbilical blood (UB), number of nucleated cells (NC); to compare manual and automatic modes of UB processing.

To characterize infectious complications arising within 30 days after transplantation of autologous hemopoietic blood cells in 42 patients with hematological malignancy (HM); to compare the course of early posttransplantation period with reference to a kind of high-dose conditioning and dose of transplanted CD34+ cells.

To develop an original therapeutic strategy in Ph-positive acute lymphoblastic leukemia (ALL).

Was studied the influence of the Thymodepressin (dipeptide D-iEW--a new Russian immuno- and haemodepressant), on the hyperthermic sensitivity of haemopoietic precursors (CFU-S) and tumor model cells (EL-4 and Rauscher leukaemia). It was determined, that the injection of the Thymodepressin to donor mice, or the incubation with the preparation of the marrowy cells of normal mice provides the increasing of the CFU-S resistance to the following heating (43 degrees C). On the contrary, Thymodepressin-treated tumor cells became even more heat-sensitive. The data show that Thymodepressin can be useful for protection the haemopoietic precursors not only from radiation and chemotherapy, as it was shown earlier, but also from the hyperthermy.

Transplantation of suspention of allogenic fibroblast-like mesenchymal stem cells (AFMSC) of the bone marrow and AFMSC immobilized on the biodegradable membrane (BM) stimulates healing of deep burn wounds compared to control (without cell transplantation) because these cells produce biologically active substances into the wound. AFMSC immobilized on BM activate repair processes in the wounds earlier. This may be due to their higher functional activity created in the monolayer by adequate intercellular interactions. To avoid complications caused by low diffuse properties of BM (protein precipitation), BM should be removed from the surface of the burn wound maximum 3 days after its application.

In the recent years the development of methods of skin revitalization (remodeling)--i.e. of its restoration after damage of any nature (including aging)--attracted the attention of not only cosmetologists and dermatologists, but also of endocrinologists, physiotherapists, surgeons and geriatrists. The skin grows old together with the whole organism, and it is impossible to deter this process only in the skin. Nowadays a series of methods is offered in the esthetic medicine, using embryonic cells, regulatory peptides and placenta suspensions to influence the aging processes both in the skin itself and in the whole organism. This adds to life quality improvement and provides for social adaptation of elderly people.

We studied reactions of the granulocytic hemopoietic stem during hypoxia of different genesis and severity. Stimulation of granulocytopoiesis was determined by an increase in functional activity of granulomonocytic precursors due to changes in feeder capacity of cells in the hemopoiesis-inducing microenvironment and colony-stimulating activity of the plasma. The development of encephalopathy caused by oxygen deficiency was accompanied by a decrease in the number of bone marrow granulomonocytic precursors due to reduction of proliferative activity (despite the increase in secretory activity of microenvironmental cells and increase in plasma colony-stimulating activity). Severe hypoxia accelerated maturation of hemopoietic cells and produced neutrophilic leukocytosis.

The number of cells expressing antigen to osteonectin was appreciably increased in the blood of coronary patients, but no cells of this kind were detected in donors. The number of CD34+ stem cells in these patients virtually did not differ from that in normal subjects. A close relationship between atherosclerosis development and presence of stromal stem cells with osteogenic potential in the blood is hypothesized.

The content of stromal precursor cells in heterotopic splenic transplants from old and young mice changed appreciably after cross transplantation to old and young animals. The content of CFC-F in the young-->old transplants decreased almost 1.5 times in comparison with the young-->young transplants, the counts of CFC-F in old-->old transplants were minimum in comparison with all other groups (2.5+/-0.1), while in the old-->young group transplants this value increased almost 8-fold (to 19.0+/-1.3) and surpassed the control level. Age-associated shifts in the splenic stromal tissue were determined by regulatory influences of the host, rather than by decreased count of stromal precursor cells in the tissue.