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Biomedical subjects

T M Fliedner

Publications and source records attributed to T M Fliedner.

At least 145 records · Page 8Linked to original sources
PubMed1980

A mathematical model of canine granulocytopoiesis.

The granulocyte cell renewal system of the dog is represented by a mathematical model consisting of the following compartments: The pool of pluripotential stem cells, the committed stem cell pool, divided into a blood and a bone marrow compartment, the proliferation pool, the maturation pool, the reserve pool and the blood pool of functional granulocytes. This chain of compartments is described by a system of non-linear differential equations. Cell losses anyplace in the system provoke increased production in all pools containing cells capable to divide. A reduced number of granulocytes in the blood pool stimulates production of a "granulocyte releasing factor" which mobilizes a rising number of cells to transit from the marrow reserve into the blood pool. The model was simulated on a digital computer. It was found to be capable to reproduce the steady state conditions and it also fits the data of two distinct experimental perturbations of the system both equally well. These perturbations are a loss of proliferating cells as it occurs after the administration of cytostatic drugs and losses of functional cells as they are induced by leukapheresis experiments of differing leukapheresis rates.

Animals↗
PubMed1980

Collection of large quantities of granulocyte/macrophage progenitor cells (CFUc) in man by means of continuous-flow leukapheresis.

Continuous-flow leukapheresis using the AMINCO Celltrifuge was performed in 35 adult volunteers for the procurement of large quantities of granulocyte/macrophage progenitor cells (CFUc) as part of the mononuclear leucocytes. The donor blood volume processed was 12 1 at a flow rate of 50 ml per min. The centrifuge speed was 800 rpm. The mean yield of mononuclear cells (MNC) per run was 12.0 x 10(9) and that of CFUc, 8.7 x 10(5). The leukapheresis did not much affect the donor blood cell concentration except the platelet concentration; this must be considered as a limiting factor for leukapheresis. The mean granulocyte contamination of the leukapheresis-derived leucocytes was only about 10%. Successive leukaphereses (with short-term intervals) in 7 donors led to significant increases in CFUc yield. The possible therapeutic application of blood stem cells in the treatment of haemopoietic failure in man is discussed.

Adult↗
PubMed1980

Rhesus incompatibility and aplastic anemia as the consequence of split chimerism after bone-marrow transplantation for severe combined immunodeficiency.

A patient with severe combined immunodeficiency received three transplants of bone marrow from the HLA-B- and -D-identical mother. The first transplantation led to a severe graft-versus-host reaction followed by immunological reconstitution. A split chimerism was found with engraftment only of the maternal lymphocytes. Five months after the transplantation an autoimmune hemolytic anemia was observed which was due to rhesus incompatibility as well as polyspecific antibodies. At the same time agranulocytosis developed and 9 mth after the first transplantation the child suffered from aplastic anemia. Two further attempts failed to engraft the maternal hematopoiesis. The child died during the treatment with cyclophosphamide as conditioning for a third transplantation.

Agranulocytosis↗
PubMed1980

Velocity sedimentation and cell cycle characteristics of granulopoietic progenitor cells (CFUc) in canine blood and bone marrow: influence of mobilization and CFUc depletion.

Populations of granulopoietic progenitor cells, as measured by the colony formation technic (CFUc), of canine bone marrow and blood were compared by velocity sedimentation and tritiated thymidine (3H-TdR) induced cell death rates. Blood CFUc were smaller than those of the bone marrow and had a lower proportion in S-phase, as reflected by these methods. CFUc which were mobilized into the peripheral blood by dextran sulfate had unaltered velocity sedimentation and cell death fraction rates. Removal of CFUc from the blood by 24-hour leukapheresis resulted in doubling of 3H-TdR suicide of bone marrow CFUc, whereas that of blood CFUc was not affected. Depending on the degree of CFUc depletion, granulopoietic progenitor cells which were larger than normal appeared in the blood and bone marrow. It is concluded that there is a subpopulation of CFUc within the bone marrow which is ready for discharge into the circulation. These cells are characterized by small size and a lower proportion in S-phase. Some bone marrow/blood barrier retains large CFUc as well as those in active proliferation within the bone marrow. One might speculate that enlarged CFUc in the bone marrow are a subpopulation which normally provides only a small influx to the total CFUc pool.

Animals↗
PubMed1980

Investigations on the pool size, proliferative state and differentiation pattern of splenic CFUC in normal dogs.

In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood volume at the same time under physiological conditions. About 16% of the splenic CFUc were in the DNA synthetic phase. In spite of the presence of CFUc in the splenic tissue, there was a lack of morphologically identifiable granulocytic precursor cells and hence no extramedullary granulocyte production. The similarities between circulating CFUc and the splenic CFUc with respect to their differentiation pattern in vitro and their cell cycle state suggest that the CFUc that reside in the splenic tissue are identical to thea CFUc population in the circulation.

Animals↗
PubMed1980

Detection of lymphocyte stimulation by flow cytometry: differences in cells from patients with and without neoplasia.

Fluorescence polarization measurements were performed to detect PHA-stimulation of peripheral lymphocytes in an early state. Single cell fluorescence was measured by flow cytometry using an epi-illumination design to avoid the influence of background fluorescence and multiscattering. By these arrangements the accuracy in the determination of P, the degree of polarization, could be improved over the usual cell suspension measurements. Fluorescence polarization measurements were performed on density specified human lymphocytes after incubation with fluorescein diacetate with and without preincubation with phytohemagglutinin (PHA). A group of healthy donors had an average polarization of P = 0.17 before and P = 0.12 after PHA-stimulation, whereas a group of patients with malignant disease showed an average polarization of P = 0.14 before and after PHA-stimulation.

Adult↗
PubMed1979

Collection, storage and transfusion of blood stem cells for the treatment of hemopoietic failure.

Migration of hemopoietic stem cells via the blood to sites of stem cell need is a principle that becomes established during the embryonic development of hemopoiesis and can be observed in the adult whenever bone marrow transplantations are being performed. The regular presence of stem cells in the peripheral blood lends itself to the study of their collection, storage, and use for transfusion purposes in cases of bone marrow failure. Both in dog and in man, granulocyte-macrophage progenitor cells (CFU-C) can be collected by leukapheresis from the blood in large quantities, particularly if the yield is increased by the administration of mobilizing agents such as dextran sulfate, and appear to be an indicator for the presence of stem cells. For collection and storage, a closed plastic bag system has been developed that allows the safe handling of the cells. The loss of CFU-C from freezing and thawing with DMSO as a cryoprotective agent is only 10%-20%. If frozen and thawed mononuclear leukocytes are transfused into 1200 rad whole-body X-irradiated autologous or allogeneic recipient dogs, a hemopoietic take is observed when 0.2 X 10(5) CFU-C are present among the mononuclear leukocytes (MNC). Graft-versus-host disease can be avoided in the allogeneic situation when a purified CFU-C rich cell fraction is being transfused. In man collection and storage of MNC including CFU-C is feasible and may eventually become a therapeutic tool.

Animals↗
PubMed1979

Reaction of human granulopoiesis to high-dose cyclophosphamide therapy.

The reaction pattern of an unperturbed human granulopoiesis to pulses of high-dose chemotherapy (cyclophosphamide 2000 mg/m2 plus vincristine 1.4 mg/m2 or adriamycin 20 mg/m2) was serially studied in 6 patients. The stem cells committed to granulopoiesis (CFU-C) of the bone marrow and the cells of the proliferative granulocytic marrow pool were considerably reduced during the first 8 days. Granulopoietic regeneration was first recognizable by increased proliferative activity of bone marrow CFU-C (3H-thymidine technique). The cytotoxic drug-induced injury to the early compartments of granulopoiesis, and granulocytic regeneration proceed sequentially through the ensuing, increasingly differentiated granulocytic compartments. In the peripheral blood, depletion and repletion of the CFU-C pool precede the corresponding changes of segmented neutrophils by 7 to 9 days; during granulocytic regeneration, peripheral blood CFU-C show a transient greatly overshooting decrease.

Bone Marrow↗