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T M Fliedner

Publications and source records attributed to T M Fliedner.

At least 163 records · Page 9Linked to original sources
PubMed1979

Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood.

Two hematologically normal patients with glioblastoma and six patients with chronic lymphocytic leukemia received continuous 3H-thymidine infusions for 3--10 days. In autoradiographs of blood cell smears taken for 25 days or more after the beginning of 3H-thymidine administration the labeling index and the labeling intensity of granulocytes were determined. A sufficiently high labeling intensity, i.e. a sufficiently long autoradiographic exposure time was found to be critical for obtaining valid and reproducible results. On the basis of certain assumptions discussed in detail, complete labeling of cells with 3H-thymidine followed by autoradiographic evaluation and mathematical analysis of the labeling patterns seems to be a suitable method for estimation of kinetic parameters of postmitotic granulocytes in vivo. The mean intramedullary maturation and storage time was observed to be 115 +/- 7 h or neutrophils, 103 +/- 4 h for eosinophils and 103 +/- 11 h for basophils. The mean relative inflow rate into the blood (or relative turnover rate in the blood) was found to be 4.2 +/- 0.4/h for neutrophils, 4.0 +/- 0.4%/h for eosinophils and 1.2 +/- 0.3%/h for basophils. The mean blood transit time (or blood sojourn time) was estimated to be 25 +/- 2 h or neutrophils, 26 +/- 3 h for eosinophils and 89 +/- 21 h for basophils. Accordingly the half lifes (T 1/2) of granulocytes in the blood were 17.3 +/- 1.4 h for neutrophils, 18.0 +/- 2.1 for eosinophils and 62 +/- 15 h for basophils. Under the quasi steady state conditions of this study the kinetics of granulocytes in the present CLL patients appeared to be normal, despite a marked lymphocytic infiltration of the bone marrow. The apparent discrepancy between these findings and the data obtained with autotransfusion of DFP-labeled granulocytes is discussed.

Aged↗
PubMed1979

Studies on the presence and possible oscillations of granulocytic progenitor cells (CFU-C) in human blood.

The presence of CFU-C in the peripheral blood of 3 healthy volunteers was monitored over a period of 70 d. Blood samples were taken 3 times a week. Mononuclear cells (MNC) were separated from blood leucocytes by dextran sedimentation and the iron ingestion method. After cryopreservation the cells were cultured in soft agar. One sample of mononuclear cells was cultured using a leucocyte feeder layer as a source of colony stimulating activity (CSA) and another sample using human placental conditioned medium as CSA. In cultures using a leucocyte feeder layer, the average number of CFU-C was 29, 43, 118 per ml blood. No systematic oscillations were observed. When human placental conditioned medium was used the average number of CFU-C was 255, 125, 222 per ml blood, respectively. Significant oscillations with periods of 23, 19 and 25 d were observed.

Adult↗
PubMed1979

[Effectiveness of gnotobiotic measures in the treatment of acute leukemia: the results of a prospective randomized clinical study].

60 adult patients with acute leukemia (AL) previously untreated or in relapse received induction chemotherapy with different types of supportive care. Group A was decontaminated by nonabsorbable antibiotics in strict reverse isolation, group B was isolated only and group C was treated under routine hospital conditions. There were less infections in group A and B compared with group C. 76% of patients in group A achieved remission, in contrast to 57% in group B and 59% in group C. Late evaluation three years after termination of the study showed that all patients were dead except four patients being in first remission after discontinuation of maintenance treatment. Three patients were treated in group A, one patient in group C. However, the differences of survival and remission rates were not significant. Failure to demonstrate significant advantage of isolation and decontamination in treatment of AL was caused by insufficient suppression of microbes by the applied antimicrobial measures. Thus, it is suggested to investigate better antimicrobial treatment before gnotobiotic care is accepted as routine supportive treatment in AL.

Acute Disease↗
PubMed1979

Collection and cryopreservation of mononuclear blood leukocytes and of CFU-C in man.

For bone marrow reconstitution after hemopoietic failure as a consequence of the action of a variety of etiological factors, hemopoietic stem cells are needed. These have been derived in the past mainly from bone marrow. This report describes studies and their results that indicate that granulocytic progenitor cells, measured in cell culture systems as "colony forming units in culture - CFU-C", can be collected in large quantities from the peripheral blood of human blood donors by continuous flow leukapheresis. They can be stored at ultra-low temperatures. Their recovery rate after thawing and washing is better than 85%. In a canine model, evidence was obtained that the presence of CFU-C in a suspension of mononuclear blood leukocytes is also indicative for the presence of pluripotent hemopoietic stem-cells. Therefore it is suggested that stem cells can also be collected from human blood as an alternative source for bone marrow reconstitution.

Blood Preservation↗
PubMed1979

Albumin density gradient purification of canine hemopoietic blood stem cells (HBSC): long-term allogeneic engraftment without GVH-reaction.

Long-term repopulation of the blood-forming organs of dogs, conditioned by wholebody X-irradiation (1200 R midplane dose), was achieved by transfusion of cryopreserved allogeneic blood mononuclear cells (MNC) without causing graft-versus-host-reaction (GVH-R). Donor and recipient dogs were DL-A identical, MLC-negative, no siblings, non-related. The blood stem cells (CFUc) were procured by a 3- to 4-hour continuous-flow leukapheresis. To increase the CFUc concentration in the peripheral blood, dextran sulfate (DS) was administered intravenously beforehand. About 1 x 10(10) MNC, among them about 1 x 10(7) CFUc, were collected and further segregated using a discontinuous albumin density gradient. Less dense cells were to be found in the upper part of the gradient (fraction 2). These cells included most of the CFUc, enriched by a factor of between 275 and 1730 compared to their concentration in the peripheral blood beforehand. After cryopreservation, these cells, when transfused into lethally irradiated dogs, completely repopulated the marrow and lymph nodes, caused no GVH-R and allowed long-term survival. These dogs received no immunosuppressive therapy, either before or after transfusion. More dense MNC were to be found in fraction 3; their transfusion caused a severe GVH-R, followed quickly by death. Fraction 4 was rich in lymphocytes and poor in CFUc. The transfusion of these cells produced a selective plasma-cell hyperplasia of the lymph nodes but failed to repopulate permanently the marrow. The reappearance of the different cell lineages in the marrow and in the peripheral blood after conditioning and transfusion of these cells produced a selective plasma-cell hyperplasia of the lymph nodes but failed to repopulate permanently the marrow. The reappearance of the different cell lineages in the marrow and in the peripheral blood after conditioning and transfusion of the segregated MNC is described in detail.

Animals↗
PubMed1979

Morphologic alterations in canine marrow of long-term survivors after 1200 R whole-body x-irradiation and autologous blood leukocyte engraftment.

The marrow matrix of total-body x-irradiated dogs (1200 R midline dose) was able to support effective hemopoiesis for several hundred days if the animals were transfused with their own mononuclear leukocytes collected from the blood prior to irradiation and preserved at ultralow temperatures. However, a lesion developed in the marrow, consisting of a fibrosis originating in conjunction with or from the endosteum. The fibrotic tissue substantially reduced the available marrow space in dogs with advanced lesions. The number of autologous, cryopreserved mononuclear leukocytes transfused ranged from 0.32 X 10(9) to 1.63 X 10(9)/kg body weight. The observation period extended to a maximum of 898 days after irradiation.

Animals↗
PubMed1978

Fluorescence-polarization changes in mononuclear blood leucocytes after PHA incubation: differences in cells from patients with and without neoplasia.

In 32 healthy blood donors, 20 patients with histologically verified cancer and 18 patients with non-neoplastic diseases, the fluorescence polarization changes of fluorescein samples incorporated in mononuclear leucotyes were measured after incubation with PHA. The leucocytes of healthy persons, and 16/18 persons with non-neoplastic diseases, responded with a decrease in the degree of fluorescence polarization by about 20% from that in non-PHA-stimulated cells. In 19/20 patients with a variety of malignant tumours, the leucotyes did not respond to PHA stimulation with such a decrease. The exceptions among the patients with neoplastic and non-neoplastic diseases are considered, and may not be "false-negative" or "false-positive" respectively, but indicative of a particular situation in that disease. The biophysical mechanisms underlying the observed changes remain to be investigated.

Adult↗
PubMed1978

Changes of granulopoiesis during and after adjuvant chemotherapy of breast cancer.

Adjuvant chemotherapy allows a study of the effects of cytotoxic drugs on natural human haematopoiesis. We describe serial studies of granulopoiesis performed during and after intermittent adjuvant chemotherapy for breast cancer (adriamycin plus cyclophosphamide, given for six courses at monthly intervals). After drug administration, a sequential wave of depletion and regeneration through successive granulopoietic compartments was observed. With repeated chemotherapy, moderate neutropenia developed, and the blood CFU-C pool size became progressively reduced. After the sixth chemotherapeutic course, granulopoietic regeneration was delayed. Following discontinuation of chemotherapy, a long-lasting (greater than 200 d) reduction of the blood CFU-C pool size, together with neutropenia and reduction of marrow segmented neutrophils, was observed, suggesting a defect of granulopoiesis with persistent granulopoietic hypoplasia. In patients with expected long survival, residual bone marrow damage should be added to the list of potential late side effects of cytotoxic drug therapy.

Bone Marrow↗
PubMed1978

Collection of in vitro colony-forming units from dogs by repeated continuous flow leukaphereses.

The presence of in vitro colony-forming units (CFUc) was demonstrated in leukocyte suspensions collected by continuous flow leukaphereses performed serially in dogs. The CFUc yield of one leukapheresis was usually between 10(4) and 10(6). Higher yields were obtained in the 2nd to 5th leukaphereses than in the first one in the same dog. The number of CFUc collected during one leukapheresis was about four times the number of CFUc present in the circulating blood at the beginning of the leukapheresis. After a diminution during leukapheresis the circulating CFUc pool was restored in 2 or 3 days with an increase in the ratio of CFUc to mononuclear cells. These results indicate that CFUc entered the circulating pool during and after leukapheresis and that the population size regulation of canine-circulating CFUc is different from that of the bulk of the mononuclear leukoytes.

Animals↗
PubMed1978

Distribution of tritiated compounds (tritiated thymidine and tritiated water) in the mother-fetus system and its consequences for the radiotoxic effect of tritium.

The incorporation and distribution of tritiated thymidine (3H-TdR) and tritiated water (HTO) have been measured in newborn rats exposed to various levels of tritium by continuous infusion into pregnant rats from day 9 until term. In the animals exposed to HTO, the tritium activity was homogeneously distributed, while 3H-TdR led to accumulation of DNA-bound and homogeneously distributed tritium. The incorporated activity and the specific activity of DNA from ovaries which showed a reduction of total oocyte number by approximately 50% were used to estimate the dose absorbed by the ovarian cell nuclei in both systems. From the absorbed dose, a factor of 3.7 was calculated for the "internal relative biological effectiveness" of DNA-bound tritium as compared to homogeneously distributed 3H under the restrictive assumption that the static description of the system at birth reflects the situation during the time of dynamic development of the ovaries when the toxic effect occurs. The influence of these dynamic factors of changing nuclear size and tritium incorporation during the sensitive period is weighed against the possibility that the continuous 3H-TdR infusion during pregnancy might represent a model in which DNA-bound tritium shows a higher effectiveness than homogeneously distributed tritium.

Animals↗
PubMed1978

Studies on the inhibitory effect of granulocytes on human granulocytopoiesis in agar cultures.

In the present study, the inhibitory effect of blood granulocytes on granulocytic colony formation from human white blood cells was tested. Attempts were made to clarify the effects of granulocytes by plating increasing numbers of polymorphonuclear cells (PMN) by using granulocytes which had been inactivated by freezing, by studying the effect of PMN removal and by observing the effect of dilution of granulocyte inhibitors to ineffective levels at different time intervals after the onset of culture. It will be shown that colony formation is inhibited by an excess of PMN and that the inhibitor is produced only by viable PMN. There is no inhibition during the early phase of the culture, thus suggesting that the CFU-C itself is not the target cell for the inhibition of colony formation in agar culture, but rather the more mature precursor cells of granulopoiesis.

Agar↗