Effects of prodigiozan on post-radiation recovery of hemopoietic precursor cells and colony-stimulating factor level in long-term cultures of mouse bone marrow

Prodigiozan injected to long-term cultures of mouse bone marrow 24 h before irradiation increased CFUs and CFU-GM number and colony-stimulating factor (CSF) level by the time of delivery of ionizing radiation. As early as 60 min following irradiation of bone marrow structures with a dose of 2 Gy the number of CFUs and CFU-GM decreased considerably, and from day 3 on after irradiation the indices under study were gradually restored. By day 14 the cultures preinjected with prodigiozan exhibited higher recovery levels. The decrease in the number of precursor cells 60 min after irradiation was accompanied by a drastic increase in the CSF content of cultures; the CSF release in cultures protected with prodigiozan was more moderate than in the irradiated controls.     

Characteristics of thymus-homing bone marrow cells

Using a short-term in vivo assay, we studied bone marrow cells capable of homing to the thymus of lethally irradiated recipients. In the bone marrow, these cells lack the T cell markers Thy-1 and Lyt. Soon after their homing into the thymus, however, the immigrants begin to express Thy-1 and Lyt antigens, but not TL antigen. Unexpectedly, Lyt antigens appear to be expressed before Thy-1. These thymus-homing bone marrow cells seem to be already separated from the B cell lineage. Most of the homing cells are engaged in the cell cycle.     

Immunoglobulin-positive cells in mouse bone marrow]

The content of Ig-bearing lymphocytes and their precursors in the mouse bone marrow was investigated 6 and 36 hours after the hydroxyurea treatment. Some increase of the B-cell content takes place in the trated bone marrow. Dividing and non-dividing B-cell precursors, except the stem cells, were practically absent.     

Immune recovery following bone marrow transplantation

83 patients undergoing allogeneic or autologous BMT because of haematologic malignancies have been studied before and after transplantation at different intervals. The determinations consisted of lymphocyte counts, E-rosetting, lymphoblastic response, evaluation of serum immunoglobulin levels, skin testing, and in a smaller part of the patients surface marker studies using monoclonal antibodies of the BL-series. At first after BMT the lymphocyte and T cell counts went to normal between 4-18 weeks post transplant, about 4 weeks earlier in autologous than in allogeneic BMT. T suppressor cells showed an early increase compared to T helper cells which normalized much slower about 6 months after BMT. Lymphoblastic responses, however, tended to normal not before the second half of the first year both in autologous and allogeneic transplantation. Skin test reactivity became normal during the 2nd and 3rd year posttransplant, which was more complete in autologous than in allogeneic BMT. The IgG and IgM levels were depressed for half a year and IgA levels for 2 years. The most striking aspect was the multiphase course of lymphoblastic response in every individual patient. We suggest this to be the expression of sequential differentiation of donor lymphocytes.     

Mitotic activity of rat bone marrow cells during injury

The mitotic regimen analysis in rat bone marrow cells was conducted 1, 3, 7, 14, 21 and 35 days after shock trauma. A sharp impairment of myelocyte reproductive function was registered against an increase in the mitotic index. It confirms a universal character of normal mitosis impairment in strong stresses, which was earlier established for epithelial tissues. Cell division disturbances in the bone marrow may be considered an pathogenic factor of a number of pathological processes occurring in the blood system in traumatic disease (anemia, immunodepression). A complex of drugs (sodium oxybutyrate, sodium oxiferriscarbon, Laevamizolum) is offered for the correction of proliferative processes in the bone marrow. This complex has no significant influence on mitotic index and causes relative reduction of pathological mitosis level, ensuring its earlier normalization.     

Hybrid resistance to precursor cells of bone marrow stroma]

A focusl of hemopoiesis appearing after the transplantation of a bone marrow fragment of C57BL mice to syngeneic mice (under the kidney capsule) contained more hemopoietic cells than in transplantation to the semisyngeneic (CBA X C57BL) FI recipient. Experiments were conducted with a secondary seeding by intravenous injection of hemopoietic cells of the C57BL transplant genotype into the transplant depopulated by irradiation; it was shown that these differences were caused by lesser dimensions of the hemopoietic microenvironment in the focus in the hybrid organism in comparison with such in the syngeneic system. Thus, the hybrid resistance was expressed not only to the hemopoietic cells, but also to the stromal precursors transferring the hemopoietic microenvironment.     

Characteristics of the cells producing thymic chemotactic factor for bone marrow stem cells

It was shown using complement-dependent cytolysis and monoclonal antibodies against CD4, CD8, and NK1.1 antigens that the cortisone-resistant CD3+4-8-NK1.1(-)-thymocytes spontaneously secreted a chemotactic transmitter inducing the release and directed migration of bone marrow cells. When estimating the general profile of the cytokines of these thymocytes by PCR with revertase, it was demonstrated the cells in question did not express cytokines with colony stimulating activities (SCF, IL-3, or GM-CSF) or cytokines affecting the migration of bone marrow stem elements (IL-2, 4, or 7). In addition, an active expression of gene bcl-2 was detected. Thus, the chemotactic cytokine inducing the release of bone marrow stem elements is a product of the cortisone-resistant long-living CD3+4-8-NK1.1(-)-T-cells of the thymus.     

Proliferative capability of nuclested rat bone marrow cells following freeze--thawing]

A study was made of the proliferative capacity of myelokariocytes of the rat bone marrow after freezing and thawing under protection of the oxyetyl derivative of the tetratomic alcohol; experiments were conducted on mouse-rat radiation chimerae. The rat bone marrow cells proved to retain their proliferative capacity.     

Characteristics of DNA replication of the chromosomes of the bone marrow cells in patients with acute leukemia]

A study of the late DNA replication pattern in chromosomes of human acute leucaemia cells revealed a significant diffrence from control. Chromosomes, 2,3 and 4-5 of the acute leucaemia cells finish their DNA replication earlier, and chromosomes 1, 13-15 and 16 later, compared to the control chromosomes. The difference in the pattern of DNA replication between analogous chromosomes of acute leucaemia and donor cells was associated with the discovery of large late-replicating chromatin blocks in the pericentromeric regions of leucaemia cell chromosomes. Some relationship is suggested between the pattern of pericentromeric heterochromatin DNA replication and cell differentiation.     

2 populations of bone marrow cells transfering the hematopoietic environment]

A bone marrow fragment transplanted under the kidney capsule created a focus of ectopic hemopoiesis, whose isze, measured by the number of hemopoietic cells, was proportional to the implant size. Dimensions of the focus proved to be 11/2--21/2 greater in the irradiated than in the intact recipients. Cells building up the focus of heterotopic hemopoiesis had a different radiosensitivity in the intact and irradiated recipients--their Do constituted about 160 and 350 rad, respectively. In this connection it is supposed that two cell populations of precursors took part in the creation of the focus. Their possible relations with the determined and inducible osteogenic precursor cells are discussed.     

Cloning stem cells in the bone marrow of irradiated mice]

Different amount of intact or irradiated bone marrow from syngenous donors was administered to mice irradiated with a lethal dose. There was revealed a linear dependence of the number of the 8-9-day colonies grown in the bone marrow of the femur on the amount of the administered cells, and an exponential dependence on the irradiation dose. Regularity of the stem cell cloning in the bone marrow was analogous to such in the spleen. Radiosensitivity of the colony-forming units (CFU) differed depending on the site (the spleen, the bone marrow) of their colony formation. The CFU settling in the marrow proved to be more radioresistant (D(0) equalled 160-200 P) in comparison with the CFU settling in the spleen (D(0) constituted 80-100 P). It is supposed that a different radiosensitivity of the CFU was caused by the presence of heterogenic population of the stem cells and also by specific peculiarities of the organ (the spleen, the bone marrow) in which the colonies formed.