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Biomedical subjects

T M Fliedner

Publications and source records attributed to T M Fliedner.

At least 127 records · Page 7Linked to original sources
PubMed1983

Survival of transfused cryopreserved granulocytic progenitor cells (CFU-C) in recipient circulation.

We have studied the pattern of CFU-C disappearance from the peripheral blood of normal and total-body-irradiated dogs given cryopreserved cell suspensions from bone marrow, foetal liver and peripheal blood containing known numbers of CFU-C under an autologous and allogeneic donor-recipient relationship. Only a small fraction of infused donor CFU-C could be detected in the circulation of recipients at the end of the infusion. There was an exponential fall in circulating CFU-C, indicating random loss of infused CFU-C. The CFU-C disappearance pattern in each experimental group was reproducible. The mean half life of autologous blood derived CFU-C in the circulating blood of normal recipients was 8.2 min and the mean blood CFU-C turnover was calculated to be 9.3 X 10(5) CFU-C/kg per day.

Animals↗
PubMed1983

Blood leukocyte responses to extracorporeal circulation. I. Short term extracorporeal circulation in dogs without and with extracorporeal irradiation.

Short term (1 h) extracorporeal circulation without or with irradiation of blood was performed in two normal dogs in a series of experiments. The granulocyte count was constantly diminished, while the lymphocytes did not show any particular change in their concentration. In the majority of the experiments a decrease of the CFU-C content occurred to less than 70% of the initial level. There was no difference in the results of experiments with or without irradiation. In the "bag to bag" procedures, no significant change in the blood leukocyte counts including CFU-C, was established.

Animals↗
PubMed1983

Blood leukocyte responses to extracorporeal circulation. II. Medium term extracorporeal circulation without and with extracorporeal irradiation in normal and splenectomized dogs.

Medium term (6-8 h) extracorporeal irradiation without and with irradiation of blood was performed in normal and splenectomized dogs to reveal the changes of blood leukocytes including CFU-C. A regular but transitory decrease of granulocytes and a longer lasting diminution of lymphocytes in the blood were observed. The CFU-C level became and mostly remained very low during the procedure. Splenectomy did not influence significantly the changes of peripheral leukocyte counts. No marked difference of leukocytes was seen in the blood samples taken from the arterial or venous side of the shunt or even from the cubital vein. Also, the irradiation did not produce any difference in the alterations of blood cell counts compared to those without irradiation. The possible explanations of these results are discussed.

Animals↗
PubMed1983

Blood leukocyte responses to extracorporal circulation. III. Long term extracorporeal circulation without and with irradiation in normal and splenectomized dogs.

Long term (12-48 h) extracorporeal circulation without and with irradiation of the blood was performed in normal and splenectomized dogs in order to observe the effect of these procedures on blood leukocyte counts including CFU-C. A transient granulocytopenia and a decrease of lymphocyte count were observed. The blood CFU-C level diminished to a very low level and remained low for the whole time of the experiments. There was no significant difference between the results of procedures with or without irradiation. The similar effect of a shortened tubing system on the blood leukocyte count is also reported. Heparin infusion alone did not decrease the peripheral CFU-C concentration. The possible explanations for the observed phenomena are discussed.

Animals↗
PubMed1983

Progenitor cell (CFUc) reconstitution after autologous stem cell transfusion in lethally irradiated dogs: decreased CFUc populations in blood and bone marrow correlate with the fraction mobilizable by dextran sulphate.

The present study in dogs concerns the functional potentials of the myeloid progenitor cell system during hemopoietic recovery after lethal total-body irradiation and autotransfusion of cryopreserved stem cells derived from peripheral blood and bone marrow. CFUc were assayed in peripheral blood and bone marrow before and at various intervals after grafting. In addition, the net increase of CFUc mobilizable from extravascular sites into the blood was determined after i.v. injection of 15 mg/kg body weight of dextran sulphate (DS). The data indicate a sustained deficiency of CFUc in otherwise hematologically normal recipients. The DS-response was subnormal even 225 days after transplantation, suggesting residual damage of the hemopoietic system is present for a prolonged period of time. A significant correlation was found between the actual blood CFUc concentration and the numbers of CFUc mobilizable by DS. Insight into progenitor cell kinetics and corresponding changes in the size of a mobilizable pool in extravascular sites may be helpful in estimating the marrow reserve of transplanted individuals suffering myelosuppressive effects of chemotherapy.

Animals↗
PubMed1983

The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation.

Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

Acute Disease↗
PubMed1982

[Medullary and extramedullary hematopoiesis in the dog after whole body irradiation and transfusion with stem cells obtained from blood].

Autologous transfusion of 2.8-39.5 X 10(9) cryopreserved mononuclear blood leukocytes (BMNC) into 1200 R wholebody irradiated dogs leads within 10 days of irradiation and transfusion to patterns of hemopoietic regeneration of bone marrow, spleen and blood the extent of which correlates with the number of granulocytic progenitor cells, measured as CFU-C, in the tranfusate. In the marrow there are erythrocytic, granulocytic and megakaryocytic foci of regeneration ("colonies") in a proportion of 10:6:1 respectively, while the spleen exhibits cell dose related regeneration of the white pulp and a (transitory) erythropoietic wave of regeneration localized in the red pulp only. The mechanisms of the development of this extramedullary hemopoiesis are unknown. However, it closely resembles the prenatal phase of splenic erythropoiesis which disappears soon after birth. The normoblasts present in the blood at day 10 after irradiation and transfusion of BMNC correlate with extramedullary blood cell formation buy not with the type and extent of bone marrow regeneration.

Animals↗
PubMed1982

Granulocytic progenitor cells (CFU-C) in canine blood: mobilization by dexamethasone?

DXM application in dogs in an amount of 0.3 or 0.6 mg/kg b.w. results in a very transient increase of CFU-C within 1 h after administration and a subsequent progressive decrease of circulating CFU-C reaching a nadir at about 7 h. The pattern seen in the blood CFU-C concentration matches the pattern of change seen in the total lymphocyte population. The CFU-C changes observed do not correspond to the change of the PMN numbers in the peripheral blood after DXM. There is a 3 fold increase in the number of circulating PMNs. The data suggest that the blood CFU-C follow in principle the pattern of the other mononuclear cells, usually described as "lymphocytes". The pattern of change of CFU-C and lymphocytes however must not be interpreted to mean that the pathophysiological mechanisms behind this changes are the same considering the CFU-C population and the other lymphocyte populations.

Animals↗
PubMed1982

Quantitative aspects of granulocytic progenitor cell (CFUc) mobilization from extravascular sites in dogs using dextran sulphate (DS).

The relationship between the increase in the blood CFUc concentration after intravenous injection of dextran sulphate (DS) and the pre-existing levels of spontaneously circulating CFUc was studied in dogs. After 15 mg DS/kg body weight the CFUc numbers per ml blood rose by a factor of 3.7 over the pre-injection values, from 78 +/- 11 (SEM) to 359 +/- 50, in normal dogs, and increased by a factor of 3.9 in 0.84-Gy-r-irradiated animals which had a reduced initial CFUc concentration per ml, from 35 +/- 8 to 116 +/- 43. The injection of 20 mg DS/kg body weight into unirradiated dogs caused an increase, by a factor of 11.5, of the pre-injection CFUc concentration, from 101 +/- 20 to 921 +/- 106. On the basis of the mobilization curves for individual dogs, a significant correlation was found between the normal blood CFUc value and the number of CFUc mobilized by DS for both dose levels. From the descending part of the mobilization curves obtained after 15 mg DS/kg body weight, kinetic parameters of canine circulating CFUc were derived. The mean blood transit time (t) was 1.4 +/- 0.5 hr and the half time (T/2) was 1.0 +/- 0.4 hr.

Animals↗
PubMed1982

Effect of low-dose whole-body irradiation on granulopoietic progenitor cell subpopulations: implications for CFUc release.

The reaction of the granulopoietic system to whole body irradiation with 0.80 and 1.60 Gy was studied in dogs by means of colony formation assays in combination with velocity sedimentation and tritiated thymidine cytocidal techniques. Depression of circulating CFUc was associated with a marked shift in the size distribution of granulopoietic progenitors in the bone marrow. This effect lasted much longer in those animals receiving the lower X-ray dose. We conclude that circulating CFUc are not a random proportion of the bone marrow but a subpopulation of cells which are smaller in size. These cells are in an equilibrium with the larger marrow CFUc, which is very sensitive to perturbations.

Animals↗
PubMed1982

Cellular composition of human fetal bone marrow. Histologic study in methacrylate sections.

The cellular composition of the human marrow was studied in thin sections of undecalcified bone 24 fetuses aged from 11 to 22 weeks of gestation, embedded in methacrylate and stained by the Giemsa method. This procedure provides much better cellular detail than the decalcified bone sections embedded in paraffin used in previous studies. Hemopoiesis is already present at the 11th week of gestation in the long bones of the extremities. The cellularity of their marrow increases during the 4th month and is abundant in the months thereafter. Its composition is similar to that of adults but differs by the presence of a large number of stromal cells and by the absence of plasma cells and lymph follicles in the fetal marrow. Differential counts for blood-forming cells and stromal elements are given for the initial period of marrow development.

Bone Marrow Cells↗
PubMed1982

Blast cell and granulocyte production in human leukemia: pathophysiological concepts based on computer simulation using discrete modeling techniques.

The granulocyte production of two patients suffering from leukemia was studied extensively by means of the tritiated thymidine method of cellular kinetics. The data obtained (1-h labeling index, pattern of cell labeling, labeling intensity, as well as other conventional parameters of bone marrow and blood) were used to develop a computer model (GPSS-language) to fit the observations. From these models, it was concluded that patients with leukemia may have an abnormal granulopoiesis, characterized by a high degree of inefficiency (premature cell death, skipping of divisions with undisturbed maturation). However, the underlying mechanisms may be quite different. While it cannot be excluded that in acute myelocytic leukemia there is a stem and/or progenitor cell pool that is highly ineffective but still capable of feeding some cells into the granulocytic pathway, it is nevertheless possible, as shown in plasma cell leukemia, that the ineffective granulopoiesis may be the result of direct or indirect interaction between the "leukemic" and the "normal" cell clone.

Agranulocytosis↗
PubMed1982

Extracorporeal irradiation of dog blood: the effects of a radiostrontium irradiator on blood stem cells (CFU-C).

The radiation sensitivity of dog blood stem cells was measured in vitro and in an extracorporeal circulation passing through a radiation field. It was established that the calculated D0 was as low as 0.45 Gy. Investigating the cell killing rate in our equipment (Buchler type 90Sr device for extracorporeal irradiation), we found an overkill situation; the dose delivered was in excess of that which would be required for the total eradication of all stem cells in the peripheral blood passing through the radiation field. Various other types of devices used for extracorporeal irradiation of blood are also reviewed.

Animals↗
PubMed1981

[Granulopoietic progenitor cells and the hemopoietic potential of a graft: a study in the dog model (author's transl)].

Four beagles received a standardized dose of 33000-44000 CFU-C per kg b.w. isolated from the peripheral blood of DLA-identical donors. Three had permanent reconstitution of hemopoiesis while in one regeneration was abortive. This indicates that the CFU-C assay is able to predict for the hemopoietic potential of a graft. However, considerable differences in the regeneration pattern of CFU-C in the bone marrow demonstrated that the number of repopulating stem cells was variable.

Animals↗