Fractions of S.flexneri 2a 516 outer membrane proteins determined by plasmid pSF140 have been shown to possess immunomodulating activity and to be capable of influencing the intensity of hematopoiesis, manifested by the stimulation of endocolony formation, the increase of the amount of splenic colony-forming units in the marrow, the increase of the pool of proliferating splenic colony-forming units of the marrow and their intensive migration into the blood. Outer membrane proteins have been shown to produce an immunostimulating effect on the functional activity of effector B-lymphocytes shortly after their injection. On the contrary, S.flexneri 2a 516/4 pSF140- outer membrane proteins produce a less pronounced effect on hematopoietic stem cells and reproduce unspecific immunostimulating effect on the formation of B-cells, synthesizing antibodies to heterologous antigen.

The effects of acetylcholine antagonists on development of the two-cell mouse embryos was studied. Etpenal-3 and etpenal-14 were shown to delay cleavage, affect cytokinesis, induce fusion of the blastomeres and arrest development at the stage of two-eight blastomeres with respect to the concentration used. Atropine, an M-cholinolytic, affects the early embryogenesis at a higher concentration than the cholinolytics with mixed effect. Acetylcholine does not prevent cleavage and compactization of the embryos and exerts a protective effect against the cholinolytics with mixed effect at the early developmental stages. The effect of atropine is weaker. The data obtained suggest the presence of structures sensitive to cholinolytics in the early mouse embryos and a possible involvement of acetylcholine in the early development of mammals.

Fibroblast populations have been dealt with like homogeneous non-differentiating cell populations until nowadays. Such undefined fibroblast populations have been predominant cell systems for qualitative and/or quantitative studies in general cell biology, biochemistry and virology, and more specialized issues like differentiation, aging, apoptosis and transformation. Most data obtained from such investigations are inconsistent to such an extent that many scientists consider the fibroblast cell system to be unsuited for studies of the molecular mechanisms of developing cell populations. When analyzed with concepts and methods routinely applied for the study of the molecular biology of cells in stem cell systems, it has been demonstrated, that fibroblast cell systems of Valo-chicken, C3H-mice, BN-rats, and man are stem cell systems. In the fibroblast stem cell system 11 cell types with biological and biochemical individuality develop along a 11-stage differentiation sequence in five compartments under the control of genetic programs. This differentiation sequence is maintained in fibroblast populations in pathological manifestations, like Duchenne muscular dystrophy, fibrosis, as well as in transformed, neoplastically transformed, and revertant cell lineages. Evidence is accumulating, which makes it very likely, that all cell systems are stem cell systems with a design resembling the nature of the fibroblast stem cell system. Nowadays research in the field of molecular cell biology is undertaken with very advanced molecular methods, but unfortunately in most instances with poorly defined or undefined biological material or cell systems.

The effectiveness of domestic alpha 2-interferon preparation reaferon was studied in vivo and in vitro for eradication of pathological hemopoietic clone in chronic myeloid leukemia. Reaferon administration for 1-30 months produced cytogenetic remission in 7%, hematological remission in 21%, partial hematological remission in 36% of the patients. Reaferon is indicated in chronic myeloid leukemia without splenomegaly. In the disease progression reaferon is uneffective. Mechanism of reaferon therapeutic action comprises three components: a direct antiproliferative effect on hemopoietic precursor cells, activation of cellular immunity, an effect on stem cell microenvironment.

Hemopoietic precursor cloning in healthy donors and patients with lymphoproliferative disorders and its regulation in donors by two novel suppressive factors (BSF and ErSF) are investigated. It is shown that the count of erythroid precursors is increased in peripheral blood of patients with non-Hodgkin's lymphoma in contrast to the count of granulocyte-macrophage precursors. BSF inhibits entirely granulocyte-macrophage, macrophage and erythrocyte colony growth. In contrast, ErSF abrogates selectively erythroid precursor cell proliferation and differentiation. The role of the above factor in normal hemopoiesis inhibition mechanism during lymphoproliferative diseases are discussed.

The liver is the leading hemopoietic organ of 5-22-week embryo and fetus. Hepatic hemopoiesis activity is assessed by concentration, total count and proliferative capacity of granulomonocytic cell precursors (GMCP). Cloning efficacy (GMCP CE) in the liver of 7 fetuses of 16-22 weeks of gestation was evaluated in vitro. Growth factor sources were: healthy subjects (fider), medium conditioned by the umbilical cord, granulocytic-macrophagal colony-stimulating factor (GM CSF), interleukin-3 (IL-3) (Shering Plough), GM CSF+IL-3, serum from patients with chronic glomerulonephritis. Morphological and cytochemical examination of the colonies was performed. There appeared different sensitivity of GMCP of the liver to growth factors. The highest CE (40.8 +/- 5.4 per 2.5 x 10(5) cells) was found in the usage of GM CSF and GM CSF+IL-3. The colonies reached 200-500 cells. Low CE occurred after addition to the culture of IL-3 evidencing for minor sensitivity of liver GMCP to this growth factor. Total count of GMCP in the liver was 43.8-146 x 10(4). Numerous GMCP and predominance of large granulomonocytic colonies in the cultures indicate enhanced activity of GMCP in the livers of 16,822 week fetuses. However, GMCP concentration in the above fetuses was 2 times lower than in the marrow of a child with normal hemopoiesis. The discussion covers the adequacy of transplantation to one child with body weight 20-50 kg of the cells obtained from the liver of one fetus 15-20 weeks old.

While immunotyping blast cells from 45 patients with CML blast crisis, we detected 5 cases with immunologically primitive blast cells. The immunological phenotype of these cells corresponded to that of primitive stem cells which are characterized by expression of CD34 and HLA-DR antigens in the absence of other immunological markers. We suggest that blast cells from these patients may undergo differentiation similar to that of primitive stem cells that implies the existence of a new immunological variant of CML blast crisis, a primitive variant. Morphologically, blast cells in 3 cases could be classified as myeloid, in 2 cases precise identification was impossible. Cytochemically, this type of cells can be defined as mixed. The patients with CD34+ phenotype do not differ clinically or hematologically from those with CML blast crisis. Blast cells with membrane marker CD34 are likely to arise in any CML phase either as a component of overall leukemic population or predominant, single subclone.

A quantitative analysis of spermatogenesis in mice and rats has shown that the response of various germ cells to cytotoxic effects of Dipin or NMU differs. The spermatogonial compartment consisting of actively proliferating cells and some stem cells are the main targets for these drugs. The advanced I order spermatocytes, spermatids and spermatozoa proved to be less susceptible. Species specific differences have been established in the character of destructive and restorative processes during spermatogenesis.

A comparative analysis of two clones of mouse embryonic stem cells (ES-D3) that underwent different number of passages was performed to determine their potencies for in vitro and in vivo development. Cells of both clones had similar morphology characteristic of undifferentiated ES cells and were capable of forming embryoid bodies in the suspension cultures. Specific alkaline phosphatase activity of ES cells was revealed by cytochemical staining. Karyotyping showed that the proportion of aneuploid ES cells increases with an increase in the number of passages. The results of experiments on chimera production using ES cells showed that the clone D3W (passage 17) is superior to the clone D3M (passage 42) in terms of both the proportion of chimeras produced and the degree of coat color chimerism in them.

The changes occurring in the proliferation and differentiation of pluripotent hematopoietic stem cells under the action of different doses of benzylpenicillin and aspisole were investigated by using models of sublethally and lethally irradiated mice. The mitogenic and mitostatic dose-dependent effects of the drugs were revealed at the very early stages of immunogenesis and hemopoiesis. These effects show themselves in different ways (depending on the predominance of T- and B-lymphocytic conditions for T-B-cooperation and so on.

A method for the evaluation of bacterial persistence in the bone marrow in association with particular clonogenic target cells was developed. The method was based on the negative selection of cells expressing microbial antigens after treatment with hyperimmune antiserum specific to a given infective agent and the subsequent quantitation of target cells thus eliminated in appropriate assays. Using this approach, we demonstrated that Mycoplasma arthritidis and L-forms of Streptococcus strain L-406 were capable of persisting in murine bone marrow in close association with CFUs-7 (a subpopulation of hematopoietic stem cells) for at least several months after experimental infection. Francisella tularensis was also found to be capable to express on the CFUs-7 membranes. Persisting microorganisms enhanced both proliferation and migration of CFUs-7.

Retrospective analysis of 80 patients with aplastic anaemia (AA) was performed in order to examine clonogenic properties of granulomonocytopoiesis precursors and to specify the extent of disorder of hemopoiesis in AA. Sharp decrease of clonogenic properties of precursors, especially in severe form of AA was established to be present in 95% of patients, while only in 5% of patients initial indexes of the clonogenic ability were discovered to be normal. After treatment with ALG, prednisolum and androgen and also after splenectomy, clonogenic ability increased appropriately in 43%, 16.6% and 76.9% of patients, although the effect was not steady. The best results were obtained after allogenic transplantation of bone marrow (TBM), when the clonogenic properties normalization was observed against the background of remission 1-3 years lasted. Thus, low indexes of clonogenic properties of the precursors of granulomonocytopoiesis in AA, and positive effect of TBM may indicate the lesion of the precursor. At the same time normal initial indexes in some patients, and diverse effect of different methods of therapy make it possible to admit the probability of the lesion of stromal microenvironment cells.

The radiosensibility of erythropoietic tissue cells was estimated on the basis of analysis of erythrocyte and reticulocyte quantity changes in peripheral blood of the victims of the disaster on the Chernobyl NPP. The radiosensibility of blood cells was evaluated in accordance with their maturity (committed, committed-and-maturing and maturing pools). The population of erythropoietic tissue cells can be divided into two groups on the criterion of their radiosensibility. The first group demonstrates the highest level of radiosensibility varying from 0.5 to 1.73 Gy (n = 1). It includes the cells from primarily committed to basophilic normoblasts. The other group consisting of polychromatophils and oxyphils is more radioresistent. Do of these groups corresponds to their maturity and ascends from 4.7 to 12.9 Gy.

The effect of diethylstilbestrol on the hematopoietic system of intact animals and on dynamics of post-radiation hematopoiesis recovery was studied. The injection of diethylstilbestrol into unirradiated animals was shown to induce the decrease in CFUs and CFU-GM content in bone marrow, the increase in granulocyte-macrophage precursors number in spleen, the decrease in proliferative activity of hematopoietic precursor cells and the rise of CSF-GM levels in the sera at the period of optimal manifestation of radioprotective effect. Mice, which were protected by diethylstilbestrol, demonstrated much more powerful recovery of CFUs, CFU-GM numbers as well as myeloid and erythroid hematopoiesis series in comparison with irradiated control animals. It seems that radioprotective action of diethylstilbestrol is provided by the initial decrease of amount of early hematopoietic precursor cells as a result of suppression of their proliferative activity that causes the increase of endogenous growth and differentiation factors levels, which induce the changes in proliferation and differentiation of hematopoietic stem cells, providing the intensification of post-radiation hematopoiesis recovery.

Radiotherapeutic activity of histone fractions H1 and H2A/H2B were studied. It was demonstrated that both fractions are able to reduce the damaging effect of ionizing radiation on spleen colony forming unit (CFU-S) population. Histone preparations stimulated colony-forming activity of bone marrow cells exposed to dose of 0.5-3.0 Gy both in the case of incubation with preparations and intravenous or intraperitoneal administration into recipients of irradiated cells. The effect of histones and accessory thymocytes on CFU-S population is compared.

On the basis of literature and author's data the topics dealt with revealing and evaluation of post-radiation repair as well as possibility of its acceleration in hemopoietic stem (colony-forming) cells are presented and discussed. Some conceptions formed in this field of science cannot be regarded as final ones and should be checked by means of different independent methods. Evaluation of stem cell repair pronouncing and its acceleration possibility is rather indefinite.