A brief historical review of concepts on stem cells is given with a stress made on the role of Russian scientists A. A. Maksimov and A. A. Zavarzin who have formulated key problems in biology of stem cells and cell renewal. Principal stages in current studies of stem cells are considered. An outline is given of traditional and recent trends in the investigations: comparative studies of tissue systems with stem cells; molecular genetic mechanisms of the self-maintainance and the differentiation of stem cells; stem cells as a subject of gene engineering.

A study was made of the effect of high radioactive contamination on the animal organism (C57BL/6 mice) and HeLa cell culture within the ten-kilometer zone of the Chernobyl A.P.S. accident. The total radiation dose, as calculated by a gamma-component, was 0.09 to 2 Gy. A long-term exposure of mice within the zone (cumulative dose of 1.8 to 2 Gy) caused a significant decrease in bone marrow stem potencies and changes in the brain vascular system; subsequent acute exposure of animals increased interferon titres in the serum to a much greater extent than a single acute exposure did. As to HeLa cells, irradiation there of with doses of 0.09 to 0.4 Gy during 15-20 postirradiation generations caused a decrease in the proliferative activity, an emergence of cells with micronuclei and of giant cells, and remote cell death.

Mice (CBA X C57BL/6)F1 were inoculated intranasally with nonlethal doses of influenza A/PR/8/34 virus (500 EID50). At different intervals postinoculation, bone marrow cells were collected from them and inoculated intravenously to lethally irradiated syngeneic recipients with the purpose of determination of the histological types of colony-forming units of spleen (CFUs). On day 3 after inoculation, inhibition of CFUs differentiation in erythroid and granulocytic directions was observed, and in 7 days only granulocytic shoot of hemopoiesis was inhibited. Lymph node cells of the donors in 3 days postinoculation inhibited the colony-forming activity of bone marrow cells of intact mice with suppression of differentiation of erythrocytes and granulocytes. The possible mechanisms of influenza virus-mediated effect on the processes of bone marrow hemopoiesis are discussed.

Heteromorphism of the contractile elements of the iris muscular tissue in chick embryos and in chickens has been studied by means of electron microscopical investigation. The leading contractile tissue of the iris is the striated muscular tissue, which is formed as a cellular-simplastic system with its own cambium-myosatellitocytes. Some cells, containing myofilaments in their cytoplasm, are related to myofibroblastic and smooth muscle differons, which functions remain to be studied. A hypothesis is proposed on existence of two sources for development of the iris muscular elements. The first-stem cells for the striated muscular tissue; at early stages of embryonal development they are included into composition of ectomesenchyme of the neural crest and migrate into the area of the muscle anlages. The second-cells migrating from the ocular cup margins and developing into the smooth myocytes of the iris.

Cellular and fibrillar organization of the hypothalamic (HLR) and mesencephalic (MLR) locomotor regions of the brain stem has been studied in cats by means of staining the nervous tissue after Nissl and Sokolyansky. Morphometric investigations of neurons in these regions has been performed in frontal and sagittal slices. Within the limits of the HLR ad MLR there are about 45,000 of neurons, which are organized as various nuclei, the MLR cells arranging in them more compactly in comparison to diffusely ++ scattering HLR neurons. Within the limits of the locomotor regions, together with the cells and powerful compact fasciculi of fibers in the tract passing, that is especially specific for MLR, there are also numerous diffusely ++ scattered fibers. A possible role of the neurons and the fibers passing in starting locomotion at activation of the locomotor areas of the brain stem is discussed.

Experiments were conducted on Wistar rats to study the comparative effect of exogenous administration of heparin (250 U) on the colony forming ability of committed myeloid precursors and the formation of erythroblast islets (EI). The results were recorded for 5 days. On the basis of the obtained data a primary selective effect of heparin on the granulocytic-macrophagal colony forming units in the diffusion chamber was revealed. The process of EI formation is affected only in the late periods (3rd-5th day) against the background of sharply stimulated myelopoiesis. A significant reduction of the number of EI is noted in this period.

A systemic approach to appraisal of the mechanisms of changes of erythropoiesis biorhythms in stress is suggested. The authors studied the daily and seasonal rhythms of serum erythropoietin (EP) level, the production of erythrocytes (PE), the kinetics of bone marrow erythroid cells, and the activity of lipid peroxidation (LPO) and G-6-PDG in peripheral blood erythrocytes in albino rats. As a stress factor hyperbaric oxygenation initiated LPO acceleration and change of PE circadian rhythm with mesor decrease. Increased production of erythrocytes with reduction of their life span was simultaneously revealed. The differences in acrophases and amplitudes of erythropoiesis values in different seasons are caused by changes of erythroid cell kinetics due to mobilization of terminal erythropoiesis.

The cells of chick embryo hematopoietic organs were cultivated together with mouse bone marrow cells in bicameral diffusion chambers under normal conditions and in activated erythropoiesis. The yolk sac cells inhibited colony formation on the 2nd, 4th days of development, the hepatic cells--on the 8th, 12th days, the splenic cells--on the 13th, 17th days, and the bone marrow cells--on the 15th day. The cells of the yolk sac sharply intensify the formation of colonies by the marrow mononuclears, in particular, on the 6th developmental day in activated erythropoiesis. The yolk sac (on the 4th, 6th days of development), the liver, and the spleen produce humoral factors which facilitate the formation of erythroid colonies by the marrow cells of mice. The cells of a 4-day-old yolk sac inhibit the formation of granulocytic colonies, and the synthesis of inhibitors ceases in a 6-day-old yolk sac. It is suggested that the synthesis of local humoral inhibitors of the proliferation of colony-forming units controls the intensity of hematopoiesis in the organ and, by reducing proliferation, facilitates the emergency of cells into differentiation independently, according to the law or under the effect of local humoral poetins.

Stimulation and inhibition of erythropoiesis were modelled in rats to study the functional condition of central macrophages of the erythroblastic islets (EI) in the bone marrow by determining the total content of lysosomes, pH of lysosomes, activity of acid phosphatase, and 3H-thymidine inclusion in DNA. The properties of the surface charges of the EI cells were judged according to the electrophoretic mobility, the number of acid glycoproteins--according to the staining of the preparations with alcian blue. It is shown that the intensity of erythropoiesis in the EI determines the studied values. Sensitivity of EI macrophages to erythropoietin was demonstrated in EI cultivation.

The article describes the dynamics of colony-forming units in diffusion chamber of tubular bone marrow compartments 1 and 7 days after a burn. It was found that under normal conditions the activity of the axial part of the bone marrow is twice that of the cortical part. After a burn the inductive capacity of the cortical part becomes equal to that of the axial part. A wider qualitative spectrum of colonies occurs due to the effect of short-distance humoral factors (eosinophils, mast cells).

Compensatory unspecific processes taking place in irradiated bone marrow stroma are caused by qualitative and quantitative reactions of the stromal cell populations to the damaging effect. The authors studied the regularities of the compensatory quantitative reaction of the stroma--the system of fibroblast colony forming units (CFUf) of guinea-pig bone marrow--to exposure to ionizing radiation. They confirmed the existence of a "reserve" of the bone marrow CFUf system whose cell elements acquire adhesive and mitotic activity in the immediate periods (60-90 minutes) after irradiation. It is shown that the character of the dose-effect curves according to the criterion of the absolute CFUf number 60-90 minutes after irradiation is determined by two processes: the death of stromal precursor cells in proportion to the irradiation dose, and activation of the "reserve" population of the CFUf system proportionally to the level of the action of the ionizing radiation. The quantitative degree of activation of the CFUf "reserve" is characterized. Radiosensitivity was appraised in vivo of two guinea-pig bone marrow CFUf populations forming dense and loose fibroblast colonies in a monolayer culture.

It was demonstrated on an experimental model of cytostatic disease induced by a course of injections (1/10 LD50 for 10 days) of antineoplastic agents with various mechanism of action (doxorubicin, vinblastine, cyclophosphamide) that persistent (for 6 months) disorganization of the morphological composition of the thymus and other lymphoid organs is attended by inhibition of the functional activity of the T-cells of the immunity system. It is suggested that the weakened control (on the part of the thymus) due to the effect of the cytostatics may lead to disorders of the processes of proliferation and differentiation of the hematopoietic cells and impairment of the bone marrow morphological composition in late-term periods after cytostatic treatment.

The number of spleen colonies formed after intraperitoneal injection of bone marrow cells increases approximately 100-fold in mice with inflammation induced by nitrocellulose filters implanted into the intraperitoneal cavity. By transplanting these filters together with cells grown on them into intact animals and replacing them with clean filters we have demonstrated that this effect is associated with inflammation focus in the peritoneal cavity rather than with CFU-S proliferation of the filter surface.

The expression of erythroblast antigen (Ag-Eb) in cell membranes during pre- and postnatal mouse development was studied by immunofluorescence using the monoclonal antibody MAE-15. Ag-Eb was detected in embryonic liver, spleen, epithelia of intestine, various glands and skin, as well as in extraembryonic tissues (yolk sac and trophoblast). In pregnant mice positive immunofluorescence was observed in placenta and on the surface of decidual cells in uterus. In adult non-pregnant mice Ag-Eb expression was detected not only in membranes of erythroid cells, but also in non-hemopoietic tissues, such as epithelia of various glands, intestine, kidney and testis, brain endothelium, basal layer of epidermis, and intercalated discs of the heart muscle. A possible role of Ag-Eb in processes of cell transport is discussed.

The effect of mannan polysaccharide on the haemopoiesis recovery in irradiated mice has been investigated. Mannan has been shown to exert both the protective and the stimulatory effect: it accelerates restoration of femur bone marrow cellularity and nucleate cell number in the peripheral blood and causes a larger initial yield and subsequent more rapid postirradiation dynamics of pluripotent haemopoietic stem cells and precursor cells of granulocytes and macrophages.

A mathematical model simulating variations in granulocytopoiesis of mammals exposed to chronic irradiation has been built. The model has been developed to take into account the chalone mechanism of hemopoiesis regulation. The model represents a system of 12 nonlinear differential equations. The modelling results have been found to be in agreement with experimental observations of variations in granulocytopoiesis of rats within a wide range of radiation dose rates. This model has been used for the first time to simulate a stimulating effect of prolonged irradiation with a low dose rate on granulocytopoiesis. Manifestations of this effect are explained. This model can be used to predict the effect of prolonged irradiation with different dose rates on variations of granulocytopoiesis in mammals.

Analysis of the otoneurological symptomatology in 32 patients with hypophyseal tumors showed that they extended most frequently into the sphenoidal sinus, the cells of the ethmoidal sinus, the superoposterior parts of the nose, and the nasopharynx. The focal symptoms of compression of the adjoining parts of the brain (frontal, temporal) were manifested in 11 among 32 cases by olfactory disorders (loss of olfaction in 4 patients, diminished olfaction in 2, olfactory hallucinations in 4 patients, and impaired recognition of odors in 1 patient). Asymmetric action of the tumor on the subcortical structures in the fronto-parietal-temporal parts was manifested by side asymmetry of the experimental nystagmus, complete spatial disorientation of the patient after the rotation test with a false sensation of collapse to the side of the slow phase of nystagmus with vigorous motor compensatory disharmonic deviation of the trunk and limbs in the direction of the rapid nystagmus phase. The effect of the giant hypophyseal tumor on the brain stem was often manifested for a large distance (simultaneously on the diencephalic level, on the level of the midbrain, and in the posterior cranial fossa). Among a group of 32 patients 18 had the decompensated phase of affection of the vestibular apparatus. The effect of the tumor on the diencephalic parts of the brain was attended by sharply intensified vestibulovegetative reactions which should be considered as a stimulation symptom. In giant cell hypophyseal tumors, however, intensification of vestibulovegetative reactions after experimental vestibular tests does not occur in many cases, which is due to death and areactivity of the diencephalo-hypothalamic structures.(ABSTRACT TRUNCATED AT 250 WORDS)

By means of heterotopic transplantation of the bone marrow interrelations of the stromal and hemopoietic tissues of the mice bone marrow have been studied at administration of dipiridamol. Effect of the drug to the hemopoiesis is realized via stem stromal cells of the bone marrow. Under the influence of dipiridamol a focus of heterotopic hemopoiesis the osteogenic component in it is present only in 30% of cases in comparison with the control. Inhibition of the stromal component proliferation is accompanied with increasing mitotic activity of the hemopoietic elements against the background of the bone marrow cellularity decrease both in the femoral bone and in the focus of heterotopic hemopoiesis. At administration of dipiridamol a phenomenon of noneffective megakaryocytopoiesis with the intrabone marrow destruction of megakaryocytes, resulting in local release of thrombocyte growth factor, which has a compensatory character.

High level expression of erythroid differentiation antigens on peripheral blood mononuclear cells associated with increased BFUe number has been identified in a malignant lymphoma patient. A possible pathogenetic role of such disturbance in leukemogenesis has been considered.