Under study was functional activity of stromal (fibroblast) and granulo-monocytic cells-precursors in bone marrow cultures of 32 patients with acute pyodestructive diseases of the lungs. The disturbance of functional activity of cells-precursors of granulo-monocytopoiesis and stromal cells-precursors responsible for regulation of hemopoiesis was established which makes for the development of leukemoid reactions and anemia in patients with acute pyo-destructive diseases of the lungs.

The chemical composition and properties of the lymphatic node extract (LNE) obtained from the porcine submandibular lymphatic nodes have been studied. It has been established that the LNE is the mixture of low-molecular weight peptides and the components of nucleic acids with the molecular mass below 2 kD. It possesses antiproliferative, immunosuppressive and antileukemic activities in vitro and in vivo. The inhibitory effect was the most pronounced in respect to lymphoid cells rather than myeloid cells of the patients with leukemia.

It is shown that the strong emotional immobilization stress in rats resulted in increased blood-brain barrier permeability and besides--in brain parenchymal vessels damages accompanied by haemorrhages and the loss of some nerve cells. The earliest and strongest brain vessel disruptions under emotional stress were found in the oral part of the brain stem reticular formation. The vessel disturbances and the damages of the neurons were found for a long time interval after immobilization stress and resulted in functional, behavioral changes and immune reactions. Locus ceruleus was found to be involved in the blood-brain barrier function regulation and due to the fact in the fortune of the neurons under the emotional stress.

Content of three classes of clonogenic haemopoietic cells (CFU-S-7, CFU-S-11 and CFU-S-ep) was determined in haemopoietic organs of mouse during embryogenesis (10, 14 and 18 day) and postnatal ontogenesis (2, 3 and 7 day, 1, 2, 3 and 18 month). CFU-S-7 and CFU-S-11 that from big splenic colonies on 7th and 11th days of transplantation are present in liver, spleen and bone marrow at all developmental stages. However their concentration and CFU-S-7 CFU-S-11 ratio change in haemopoietic organs. CFU-S-ep that form small colonies on 11th day are observed before birth in liver and spleen and 1 week after birth there and also in bone marrow but are practically absent from haemopoietic organs of older animals. Thus, CFU-S compartment structure is characterized by definite ratio of its subpopulations. It seems to reflect functional state of haemopoietic system during development.

The experiments have been performed on white non-inbred rats, subjected to intragastric injection of cadmium chloride (7.5 mg/kg) during the whole period of pregnancy. Morphological analysis has been performed on the state of the main links in mononuclear phagocytes system (osseous-medullary precursors, monocytes of blood and alveolar macrophages of lungs), using cytological, cytochemical and electron microscopical (scanning electron microscopy) investigation methods. Changes in the cell enzymatic activity, inhibition of adhesiveness and lesion of the superficial architectonics of blood monocytes and pulmonary macrophages have been revealed against the background of their increased phagocyting activity. This demonstrates certain decrease in nonspecific resistivity of the organism, when the embryotoxic effect is developing.

It was shown on the exogenic colony-forming unit (CFU) assay that the chorionic gonadotropin (CG) administration to female mice CBA in doses correlating with its concentration in different stages of woman pregnancy stimulated (depending upon the doses) the CFU formation of bone marrow, but not spleen origin. Injections of CG to the ovariectomized mice has the opposite (inhibited) effect on the CFU contents in bone marrow and spleen. CG-administration in the dose of 40 U1 to the ovariectomized and non-castrated irradiated recipients bone marrow cells stimulates (statistically significant) colonies formation. As for 200 U1 dose hormone has the similar effect only on the non-castrated animals.

Cytogenetic disorders in hemopoietic cells of the bone marrow were studied on mice CBA at early and late periods after exposure to MIDs of doxorubicin, an anthracycline antibiotic. It was shown that at the early period doxorubicin induced aberrations, mainly of the chromatid type, in the hemopoietic cells of the bone marrow. Instability of the genetic apparatus of the hemopoietic cells observed for 3 months of the experiment was likely to be the immediate cause of the disorders in hemopoiesis at the late periods after exposure to doxorubicin.

Characteristics of lymphocyte populations in the bone marrow and peripheral blood were comparatively analyzed in children with non-T acute lymphoid leukemia (ALL) during remission, and in the reference group of children with conditionally normal hemopoiesis, as well as with population of lymphocytes obtained from the femur of 22-32-week fetuses. The analysis has shown pronounced changes in the children during remission. The shifts in the structure of lymphocyte population in the bone marrow of children during remission of non-T ALL are considered as compensatory, under conditions of a secondary immunodeficiency due to an abrupt diminution of the absolute number of bone marrow and circulating lymphocytes.

Reference values of the number and proliferation index (PI) of stromal fibroblasts in children have been presented: CFUf per 10(5) = 57.0 +/- 4.1; CFUf in 1 microliters = 85.4 +/- 8.1; PI = 1.7 +/- 0.05. It has been shown that the number of stromal fibroblasts increases in the prepubertal period, especially in girls. No relationship has been observed between CFUf and the number of platelets and megakaryocytes in the children investigated. Correlation has been established between the number of bone marrow clonogenic fibroblasts and the amount of myelokaryocytes and the number of granulocytic-macrophagal precursors in the bone marrow.

Cultural, ultrastructural, cytochemical and histological investigations of bone marrow tissue were conducted in 26 patients with varying types of preleukemia states. A number of early structural, morphological and functional signs of hemopoietic disorders of different character and manifestation degree have been revealed. Particularly, a relationship has been established between the pathologic changes appearing in the bone marrow stroma and disorders in the morphological and functional state of the hemopoietic cells.

It was found that at the time when cystamine and mexamine exert their maximum radioprotective action DNA synthesis rate decreases in bone marrow cells, the ratio between the colony-forming units in the bone marrow and peripheral blood changes, and functional activity of neutrophils increases.

Parenchymatous and stromal cells in colonic adenocarcinomas were studied electron-radiographically. The properties of the nucleic acid and protein synthesis in the cylindrical and goblet cells in carcinoma (partial 3H-thymidine incorporation, heterogeneity of 3H-uridine and amino acid mixture incorporation) indicate a relatively low level of their differentiation, lower degree of their participation in a specific function, retaining their capacity to proliferate. A high number of 3H-thymidine-labelled stem cells which are the main source of tumour growth is observed in carcinoma. Stroma in carcinoma is characterized by endotheliocyte and fibroblast proliferation (3H-thymidine incorporation), high degree of metabolic processes in some of these cells (3H-uridine and amino acid mixture incorporation) and by the disturbance of immunocompetent cell specific function (partial and weak labelling of the immunocompetent cells with 3H-uridine and amino acid mixture).

A complex of experimental original laboratory findings is presented to demonstrate a restricted proliferative potential of stem hemopoietic cells. Development of new methodologies to study primitive stem hemopoietic cells, i. e. the cells that are responsible for maintenance of continuous blood formation, allowed for confirming their existence, assessing their content in the hemopoietic tissue, determining the time and site of their embryonic origin, and for showing their limited capacity for regeneration. The obtained evidence is important for the understanding the mechanisms governing hemopoiesis.

The clonogenic activity of tumors and blood marrow cells has been studied in experiments on CBA, BALB/C and C57B1/6 mice with the Ehrlich adenocarcinoma and Lewis lung carcinosarcoma treated with adaptogenic drugs of Rhodiola Rosea extract, a synthetic analog of Rhodiola phenol derivative, methyluracil and their combinations with cyclophosphamide. The extract and derivative are shown to protect the myelopoietic tissue from the toxic action of cyclophosphamide, retaining or increasing the suppressive effect of the latter towards clonogenic tumors cells. These data can be the reason for using the extract and derivative during the antitumor chemotherapy as biological response modifiers.

The effects of a synthetic prostaglandin E1 (PGE1) analog on colony-forming activity in agar cultures of peripheral blood and bone marrow was studied in 28 patients with chronic myeloid leukemia and 9 hematologically healthy subjects. Addition of PGE1 to normal bone marrow culture was followed by a significant drop in the number of colonies per dish in 8 out of the 9 subjects. In leukemic patients, the effect was bizarre. It proved to be in correlation with survival thus suggesting that the effect of PGE1 on colony-forming activity of granulocyte-macrophage precursors be used in predicting survival in patients with chronic myeloid leukemia.

In the past years the authors advanced a hypothesis of the "age-associated layers" of parent hemopoietic cells. The hypothesis was based first of all on the differences in the patterns of leukemias and noncancerous diseases (of the hemopoietic tissues) in children and adults. The nature of the changing age-associated characteristics of parent cells remained obscure. Analysis of leukemias and epithelial tumors of radiation nature, formed in the victims to nuclear bomb explosion in Japan in 1945, analysis of leukemias occurring in persons with genetic diseases characterized by the known chromosomal aberrations (Down's syndrome, Louis-Bar syndrome, etc.), studies into the inherited forms of leukemias (chronic lympholeukemia, subleukemic myelosis, etc.--all these conditions are marked by the unstable genetic apparatus and high mutability) allowed the authors to make a conclusion about a kit of active differentiation genes which are replaced in health with age. Cancerous transformation may take place just at the level of those genes in parent cells with an unstable genome, since there appear specific mutation (in contrast to nonspecific ones characterizing the unstable genome) and a cancerous clone.

An electron microscopic study of murine oval cells, induced by a single injection of genotoxic agent dipin and by a partial hepatectomy, has shown that their ultrastructure and direction of differentiation depend on localization in the liver lobule. Oval cells around portal tracts go through three stages of development: low differentiated cells 4.40 +/- 0.51 mu in diameter with ovoid nuclei 3.43 +/- 0.44 mu, intermediate cells, and young hepatocytes. They form common ducts surrounded by a basal lamina, and produce bile canaliculi-like structures and intermediate junctions between them. Another part of the oval cell population is organized similar to the bile duct epithelium. It consists of cells 9.37 +/- 1.1 mu in diameter with nuclei 7.28 +/- 1.16 mu in diameter and form a system of branching and anastomosing ducts widespread along the parenchyma from the portal to the central veins. Our data indicate that the oval cells can differentiate into hepatocytes, and support a hypothesis according to which the cells of terminal bile ductules are liver epithelial stem cells which can differentiate into a hepatocyte or a bile duct cell lineage in periportal microenvironment.

The inhibiting activity of bone marrow fibroblasts and their ability to sustain survival of granulocytic cell precursors have been studied in patients with chronic myelocytic leukemia, chronic lymphoproliferative disorders, acute leukemia, myelodysplastic syndrome. Fibroblast conditioned medium inhibits proliferation of granulomonocytic precursors stimulated by leucocyte feeder layer or leucocyte conditioned medium. The effect depends both on the presence of monocytes and the specificity of the disease. The inhibitory effect is related with long-ranged factors. Bone marrow fibroblasts are able to sustain survival of hemopoietic precursors via humoral and cell-cell mechanisms. The regulatory role of bone marrow fibroblasts in hemopoietic disorders is discussed.

The influence of the previous cultivation of human peripheral blood mononuclear cells in suspension with mitogen on the consequent PHA-stimulated response in suspension and agar cultures was studied. It has been established that proliferative response of mononuclear cells in suspension with mitogen is not changed, but the intensity of T-cell colony formation in two-layer agar systems in increased after preincubation mainly at the expense of increasing the number of type II colonies and clusters. It is concluded that the free cell-cell contacts are needed to activate T-lymphocyte colony precursors.