Biomedical subjects
Publications and source records attributed to Iu M Zakharov.
The review describes physiological responses of cells to oxygen concentration mediated mostly by action of hypoxia-inducible factor-1, as well as the role of this factor in erythropoietin production and induction of mammalian genes by hypoxia.
Comparison of influence of erythrocytes of different stages of maturity, and their amount on erythropoiesis in erythroblastic island culture revealed their dose-dependent and maturity-dependent inhibiting effect on erythropoiesis. Erythrocytes of polycythemic rats inhibit maturing and formation of erythroblastic islands more intensively than erythrocytes of normal on anemic rats.
Joint cultivation of small amounts of young and mature erythrocytes with bone marrow erythroblastic islands during 24 hours in liquid culture system results in erythropoiesis stimulation due to increase of number of cells in the state of mitosis in island's "crown". Prolonged joint cultivation and/or joint cultivation with plenty of premature and mature erythrocytes leads to inhibition of the erythropoiesis in the state of mitosis in the island's "crown". The maximum of the inhibitory effect was shown by erythrocytes from polycythemia rats.
Erythroblastic islands of the bone marrow are morpho-functional units of erythropoiesis. The functional state of erythroblastic islands' cells of the bone marrow was for the first time defined by estimation of activity of the nuclear organisers of the central macrophages in the erythroblastic islands cultivated for 24 hrs in presence of various doses of the colony-stimulating macrophage factor. The findings indicate that increased doses of the colonystimulating macrophage factor was accompanied by a respective enhancement of the activity of nucleolar organisers in central macrophages of erythroblastic islands.
The erythroblastic islands of the bone marrow are morphofunctional units of erythropoiesis. In this work the functional state of erythroblastic islands' cells of the bone marrow, for the first time, was defined by the estimation of the activity of the nucleolar organizers of central macrophages in the erythroblastic islands, cultivated during 24 and 48 hours with the presence of various doses of erythropoietin. The findings indicated that the increase in doses of erythropoietin was accompanied by the corresponding increase of the activity of nucleolar organizers in central macrophages of erythroblastic islands. The nucleolar organizers of central macrophages in cultures of erythroblastic islands responded to very small doses of erythropoietin by their activation.
New approaches to studying erythropoiesis in man and animals on the basis of a quantitative and qualitative analysis of this process in the erythroblastic islands of the bone marrow are shown. Experimental and clinical data are given, which reflect the results of testing these approaches. Ideas on physiological and compensatory erythropoiesis in the erythroblastic islands of the bone marrow and on the manifestations of its suppression in these intercellular associations are presented.
The authors propose a functional system defining an optimal level of red cells in the body. Reception, reverse afferentation, central and actuating mechanisms of the above functional system are considered. Self-regulation of the system in hypoxia, erythrogenesis processes are outlined.
The paper presents the currently available data on hemopoiesis-regulating signalization, on the reception of hemopoietic hormones, on the role of nerve signalization and extracellular matrix in the development of a hemopoietic response adequate to environmental influence on the body.
The erythroblast islands of the bone marrow are the morphofunctional units of erythropoiesis. In this work, the functional state of erythroblast islands' cells of the bone marrow for the first time was defined by estimation of the activity of the nucleolar organizers of erythroid cells in the erythroblast islands cultivated during 24 and 48 hours in presence of various doses of erythropoietin. The findings indicated that an increase in doses of erythropoietin was accompanied by a corresponding increase of the activity of nucleolar organizers in erythrokaryocytes of erythroblast islands. The nucleolar organizers of erythroid cells in cultures of erythroblast islands responded with activation to very small doses of erythropoietin; besides, a proliferative response of erythrokaryocytes was observed after activation of the nucleolar organizers.
A 24-hour cultivation of erythroblast islets (El) in presence of erythropoietin (EP) and macrophage colony stimulating factor (MCSF) led to a concentration-dependent enhancement of phagocytic activity (PA) of the El's "central" macrophages. The latter phenomenon was revealed in "mature" El classes only. The PA of "central" macrophages in "proliferating" El appeared to be affected neither by EP, nor by MCSF.
Comparing the cell composition of erythroblastic islets containing leukocytes with those cultivated in presence of erythropoietin, the mat proliferating islets were found to contain lymphoid cells while mature islets contained granulocytes. In 72 hours of cultivation the number of islets containing lymphoid cells increased whereas the granulocytes containing islets decreased in number.
Spleen veins ligature (SVL) led to acute congestive splenomegaly in rats with subsequent normochromic anaemia disappearing on the 21st day after the SVL. An appreciable depression of the bone marrow erythropoiesis, particularly of the so called "proliferating erythroblastic islets" number, was evident on the 7th and 14th days of post-SVL period. The post-SVL anaemia was also associated with occurrence of the "islets" missing central macrophages and eosinophil-enriched "islets" in bone marrow.
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The paper presents the results of recent studies of the molecular and cell-cellular mechanisms of physiological regulation of the differentiation and proliferation of erythroid cell precursors and the reproduction of erythropoietin in the kidneys, hormone-sensitive cell reception, the mechanisms of transduction of an erythropoietic signal from the receptor of a cell to its genome, the mechanisms of erythropoietic cell-cellular interactions in the bone marrow.
When erythropiesis is stimulated (acute blood loss) or inhibited (posttransfusion polycythemia), there are early changes in the cytochemical values of erythroblastic islets (EI): in the levels of acid and neutral glucoconjugates and in the activity of nonspecific esterase. A close correlation has been found between the erythropoiesis in EI and its functional characteristics. It is concluded that central macrophages play the key role in the modulation of EI erythropoiesis. It is suggested that EI macrophages are involved in the provision of bioenergetic and reparative processes in EI.
Proliferative effects of increasing concentrations of erythropoietin were studied in vitro. The maximal amount of erythroblastic islands consisting of residual macrophages and erythroid cells was observed with the doses 0.5 to 1.5 ME/ml of erythropoietin. Smaller doses stimulated the reconstruction of erythroblastic islands.
Administration of erythropoietin enhanced the intensity of the phagocytosis in the erythroblastic island. The effect was more evident in case of normal erythropoiesis. The phagocyte activation of the central macrophage erythroblastic island was shown to depend on the condition of erythropoiesis in the erythroblastic island crown.
Administration of erythropoietin augmented the mitotic activity in the erythroid crown of erythroblastic islands in polycythemic as well as normal rats. The phenomenon seems to be due to activation of erythropoietic synthesis by the central macrophage in reconstructing erythroblastic islands.