[Pathophysiology of chronic radiation exposure of the body].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
T M Fliedner
Publications and source records attributed to T M Fliedner.
Growth and cytogenetic characteristics of bone marrow colonies from patients with 5q-syndrome.
Early erythroid precursor cells and myeloid progenitor cells (CFU-GM) from four patients with 5q-syndrome were cultured in order to study the in vitro growth patterns and to determine the clonal origin of this hematologic disorder. Cultures of CFU-GM exhibited normal colony growth, while erythroid progenitor cells demonstrated a marked decrease or absence of colony growth. Chromosomal studies indicate the 5q-chromosome is present in both hematopoietic progenitor cells, suggesting that the syndrome is an acquired clonal disease arising from a pluripotent hematopoietic stem cell. Follow-up cytogenetic studies reveal a decrease in the number of normal metaphases. This finding is consistent with reports that emphasize the slowly progressive nature of this malignant stem cell defect.
Aged↗
Canine blood mononuclear cells mediate contact-dependent impairment of granulocyte-macrophage colony formation by bone marrow cells.
Nonphagocytic, nonadherent mononuclear cells from canine peripheral blood (PBMC) were shown to suppress colony formation in agar of autologous and allogeneic bone marrow granulocyte-macrophage progenitor cells (CFU-GM). Suppression required previous cell-to-cell contact in liquid culture between PBMC and bone marrow cells (BMC) and was time- and dose-dependent and resistant to x-irradiation with 20 Gy. Small BMC were less susceptible than large BMC, whereas day-7 and day-14 CFU-GM were equally suppressed. Cryo-preservation of BMC did not enhance CFU-GM inhibition. Spontaneous inactivation during liquid culture of CFU-GM or accessory cells by PBMC is the likely effector mechanism. Possible recognition structures are different from dog leukocyte antigens A and B. Canine PBMC or subpopulations thereof might participate in the regulation of normal hemopoiesis and in the rejection of hemopoietic stem cell grafts by natural killer cell-like mechanisms as has been suggested for human and murine natural killer cells.
Animals↗
In vitro induction of B cell differentiation in canine mononuclear blood cells: bacterial lipopolysaccharide modulates the action of pokeweed mitogen.
Pokeweed mitogen (PWM) was shown to induce the generation of plasmacytoid cells (PC) from canine peripheral blood mononuclear cells in vitro. PC were detected by immunofluorescence staining of cytoplasmic immunoglobulin. Optimal culture conditions for PC formation were established and the range of the PC response in normal dogs assessed. Addition to PWM of bacterial lipopolysaccharide enhanced PC formation in most instances. This occurred in the absence of increased cell proliferation and without altering the time course of the response. Mitogen-induced PC generation may provide a useful tool for delineating the capacity of canine blood cells to mount a humoral immune response.
Animals↗
Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow.
Immunological reconstitution by transplantation of HLA-haploidentical, paternal bone marrow was attempted in four infants with severe combined immunodeficiency who lacked HLA-identical donors. To prevent graft-versus-host disease, T lymphocytes were removed from the grafts by agglutination with soybean agglutinin and rosette formation with sheep red blood cells. None of the patients received conditioning treatment before transplantation. Normal, donor-derived cellular immune functions developed in all four patients within several months of transplantation. Threatening complications of graft-versus-host reactions were not seen. All four patients remain in excellent health 12-15 months after discharge home, with persisting normal T-cell functions.
Bone Marrow↗
[Autologous bone marrow transplantation].
Explore the source record for details and available documents.
Animals↗
Developmental age estimated by bone-length measurement in human fetuses.
The lengths of 491 long bones of the extremities derived from 193 freshly delivered human fetuses of 7 to 22 weeks fertilization age were measured. Fetuses delivered after spontaneous abortion, twin pregnancy, or known maternal disease were excluded. The correlation between fetal age (measured by crown-rump length) and bone length was linear. The term "developmental age" was used for bone length-derived age values. Developmental age can be determined from the length of even a single bone, i.e., when mechanical injury of the delivered fetus inhibits crown-rump length measurement. The results could aid researchers dealing with human embryology, clinicians performing fetal tissue transplantation, and could be applied in forensic medicine as well.
Anthropometry↗
Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras.
Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration.
Animals↗
Characterization of erythroid and granulocyte monocyte progenitors in human cord blood.
Some characteristics of both erythroid and granulocyte monocyte progenitors in human cord blood were compared to those in adult blood and bone marrow. The number of progenitors in cord blood was higher than that in adult blood and bone marrow. Most colonies in cord blood culture were monocyte-macrophage, whereas those from adult blood were largely eosinophilic. Cord blood progenitors had a slower sedimentation velocity than that reported for marrow, but sedimented faster than that for adult blood. A significant proportion of progenitors in cord blood as well as adult marrow was found to be in the DNA synthetic phase of the cell cycle whereas progenitors in adult blood were not. Cord blood BFU-E were more resistant than adult blood BFU-E but cord blood CFU-GM were not different from adult blood CFU-GM with regard to radiation sensitivity. Cord blood CFU-GM appeared to be more radio-resistant than adult marrow GFU-GM. From these results is seems clear that progenitors in cord blood differ in some aspects from those in adult blood and bone marrow.
Bone Marrow Cells↗
[Remarks on the physiology and physiopathology of aging].
Explore the source record for details and available documents.
Adaptation, Physiological↗
Dose- and time-related quantitative and qualitative alterations in the granulocyte/macrophage progenitor cell (GM-CFC) compartment of dogs after total-body irradiation.
The effects of single-dose total-body X irradiation (TBI) on the granulocyte/macrophage progenitor cell (GM-CFC) population in bone marrow and blood of dogs were studied for dose levels of 0.78 and 1.57 Gy up to 164 days after irradiation. The blood GM-CFC concentration per milliliter was depressed in the first 7 days in a dose-dependent fashion to 5-16% of normal after 0.78 Gy and to between 0.7 and 5% after 1.57 Gy. The bone marrow GM-CFC concentration per 10(5) mononuclear cells, on the other hand, was initially reduced to about 45% of the average pre-irradiation value after 0.78 Gy and to 23% after 1.57 Gy. The regeneration within the first 30 to 40 days after TBI of the blood granulocyte values and the repopulation of the bone marrow GM-CFC compartment was associated with both a dose-dependent increase in the S-phase fraction of the bone marrow GM-CFC and a dose-dependent increase in colony-stimulating activity (CSA) in the serum. The slow repopulation of circulating blood GM-CFC to about only 50% of normal even between days 157 and 164 after TBI could be related to a correspondingly delayed reconstitution of the mobilizable GM-CFC subpopulation in the bone marrow.
Animals↗
Ontogeny of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the beagle.
The pattern of development of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the course of canine ontogeny was studied by means of the agar culture technique. Colony formation was stimulated by colony stimulating activity (CSA) in serum from lethally irradiated dogs in combination with erythrocyte-depleted peripheral blood leukocytes from normal adult dogs. The colonies thus obtained in cultures from the different organs were in general large (estimated maximum 50 000 cells) and consisted predominantly of mononucleated macrophages, suggesting that, in these studies, a progenitor cell with high proliferative potential (HPP-CFC) has been monitored. In the yolk sac, a transitory GM-CFC pool became established between day 23 and day 48 of gestation, reaching maximum numbers of approximately 41 X 10(3) per organ on days 36/37. At the same time the GM-CFC concentration in blood collected from the heart also reached a maximum of about 31 X 10(3)/ml, indicating its carrier function for the migration of GM-CFC. In the liver a quasi-exponential increase in the GM-CFC numbers took place between days 36/37 and days 57 to 59 when a total of about 15.2 X 10(6) was found but thereafter and up to day 4 post partum the GM-CFC numbers decreased by almost two orders of magnitude. A continuous increase in the GM-CFC numbers was found in the spleen between day 42 of gestation and day 4 post partum when a maximum of 5.1 X 10(6) to 8.7 X 10(6) was reached. In contrast to the GM-CFC numbers in the liver, the splenic GM-CFC dropped only by 50% of peak values when the dogs reached adulthood. The bone marrow always had the highest incidence of GM-CFC, the concentration per 10(6) cells being 18.7 X 10(3)/10(6) cells on days 45/46, the earliest time point at which cultures could be set up. The absolute GM-CFC numbers in the two femora increased continuously between days 45/46 and day 4 post partum in parallel with the growth of the bones. In the thymus a relatively small population of GM-CFC developed between days 42 and 48 of gestation that was kept quite constant at average numbers between 13 X 10(3) and 30 X 10(3) up to day 4 post partum.
Animals↗
Stem cells from peripheral blood and bone marrow: a comparative evaluation of the hemopoietic potential in the dog.
The kinetics and pattern of hemopoietic recovery after supralethal total-body irradiation (TBI) were compared after transfusion of cryopreserved autografts derived from peripheral blood and bone marrow. Fractionated TBI was given in three doses of 6 Gy each at intervals of 48 h. Grafts of peripheral blood mononuclear cells (MNC) were collected by means of continuous-flow centrifugation and by using the mobilizing agent, dextran sulphate. Autografts were adjusted to contain equal numbers of committed progenitor cells (CFU-GM). Dogs grafted with blood-derived MNC (group A) and with MNC from bone marrow (group B) all received about 1 X 10(5) CFU-GM per kg body weight. In all dogs consistent hemopoietic engraftment was achieved. Comparing the pattern of regeneration of the granulocytes, group A dogs showed a significant regeneratory advantage over group B dogs, particularly during the first 20 days after transplantation. Lymphoid recovery was more rapid in group A until day 14. In both groups, blood lymphocytes remained below normal values beyond day 100. The regeneration patterns of the platelets and reticulocytes revealed no significant differences. These results are in agreement with the hypothesis that there are differences in the relationship between CFU-GM content and hemopoietic potential of autografts from different sources.
Animals↗
Stimulation of extramedullary hemopoiesis by dextran sulfate.
The spleen of normal dogs (beagles) shows only slight hemopoietic activity, characterized by the presence of megakaryocytes in mitosis and small groups of erythroblasts scattered throughout the red pulp of the organ. Repeated intravenous injection of dextran sulfate, at a dose of 15 mg per kg body weight, produced markedly enhanced erythropoietic and megakaryocytopoietic activity in the splenic red pulp, without concomitant increase in splenic granulopoiesis. The probable existence of a micro-environment adequate for erythro- and megakaryocytopoietic differentiation of stem cells is discussed.
Animals↗
Autologous transplantation of a bone marrow graft manipulated by chemoseparation to eliminate residual tumor cells.
An autologous bone marrow transplantation (ABMT) was performed in a 45-year-old male patient with AML in therapy-resistant first relapse including CNS-disease. The marrow graft was harvested 18 months before, at the beginning of first remission, and was subjected to an in-vitro incubation with 4-hydroperoxycyclophosphamide (4-HC) prior to cryopreservation to eliminate residual clonogenic tumor cells. After myeloablative therapy with high-dose Cyclo-phosphamide (CY), total body irradiation (TBI) and intrathecal application of Methotrexate (MTX), the manipulated marrow graft was reinfused. The myelopoietic reconstitution started already 6 days after ABMT and was completed 40 days thereafter. There is evidence for a complete remission in marrow and spinal fluid observed over a period of 4 months.
Bone Marrow↗
In vitro studies on the sensitivity of canine granulopoietic progenitor cells (GM-CFC) to ionizing radiation: differences between steady state GM-CFC from blood and bone marrow.
The radiosensitivity of the granulopoietic progenitor cells (GM-CFC) from blood and bone marrow of dogs under steady state conditions was studied by in vitro irradiation with 280kV X-rays (approximately 0.56 Gy/min). The dose-effect relationship for colony formation was determined for the dose range from 0 to 3 Gy by means of three different models. A simple exponential function revealed an optimal approximation to the experimental data obtained for the clonogenic cells from the two different sources. The D0 values are 0.261 +/- 0.009 Gy and 0.600 +/- 0.011 Gy for the GM-CFC from blood and bone marrow, respectively. Irradiation of blood-derived GM-CFC in the presence of pre-irradiated bone marrow cells or irradiation of bone marrow cells as a mixture with pre-irradiated blood cells led to small changes only in the survival curves. According to the dose-effect relationship obtained from these studies the GM-CFC of the dog seem to be the most radiosensitive clonogenic haemopoietic cells among the different mammals.
Animals↗
Preservation of haemopoietic progenitor cells.
Explore the source record for details and available documents.
Blood Preservation↗
Chronic myelocytic leukaemia: cytogenetical studies on haemopoietic colonies and diffusion chamber cultures.
In 20 patients with chronic myelocytic leukaemia in the chronic phase or in blast crisis, several in vitro (CFU-C, BFU-E) and in vivo (diffusion chamber) culture techniques were used to demonstrate the existence of a still diploid cell clone. In 4 out of 12 patients in the chronic phase, Ph1-negative metaphases were found in the various cultures for haemopoietic progenitor cells but not in the standard suspension cultures used for cytogenetics. However, all the 8 patients investigated during blast crisis had only Ph1-positive and other abnormal clones, indicating the loss of the diploid clone during progression of the disease.
Acute Disease↗