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Biomedical subjects

T M Fliedner

Publications and source records attributed to T M Fliedner.

At least 199 records · Page 11Linked to original sources

The repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes.

Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after tranfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFUc). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 X 10(9) MBC or more. These values were obtained when 5 X 10(5) CFUc or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs tranfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow.

Animals↗

[Collection of hematopoietic stem cells from canine peripheral blood and their ability to regenerate hematopoiesis].

A procedure is presented for the collection of a large number of hemopoietic stem cells from the peripheral blood of dogs by means of a single leukapheresis using the NCI-IBM Blood Cell Separator. In the course of a leukapheresis of about 285 min duration a mean of 23 x 10-9 leukocytes is collected from the blood. The hemopoietic stem cells among such separated leukocytes initiate repopulation of bone marrow within 10 days after whole body X-irradiation with 1200 R. The cell numbers in a defined histological section of femoral bone marrow are evaluated 9 to 10 days after irradiation and subsequent autologous transfusion of 6.72 x 10-9 separated mononuclear leukocytes. The results indicate that the bone marrow cell numbers of transfused dogs are significantly greater than in dogs given only 1200 R and reach a level of approximately 49% of the normal value. Possible ways of increasing the yield of hemopoietic stem cells from the peripheral blood will be considered.

Animals↗

Bone marrow transplantation for aplastic anaemia from a HL-A and MLC-identical unrelated donor.

Bone-marrow transplantation (BMT) from an unrelated, HL-A-phenotype-identical, MLC-negative donor was performed in a 31 year old woman with severe longlasting aplastic anemia. In vitro assays failed to demonstrate humoral or cellular sensitization of the recipient against donor-type antigens. Following conditioning with cyclophosphamide, prompt but only transient engraftment of the transplant occurred accompanied by signs of mild graft-versus-host-disease (GVHD) of the liver. The results of a second bone marrow transplantation from the same donor cannot be evaluated due to early death of the recipient. It is concluded that bone marrow from unrelated, HL-A and MLC-identical donors may engraft without severe GVHD. Rejection of the graft in our patient may have been related to greater antigenic differences that can be expected to exist between HL-A and MLC-identical unrelated individuals than between HL-A and MLC-identical siblings. However, insufficient preparative immunosuppression with cyclophosphamide due to severe hepatic hemosiderosis appears equally likely as the cause of graft rejection. The possibly increased risk of graft rejection or severe GVHD should not preclude the use of unrelated HL-A and MLC-identical marrow donors, when histocompatible sibling donors are not available; but more potent immunosuppressive regimens than the cyclophosphamide protocol may be necessary to ensure permanent engraftment.

Adult↗

Autotransfusion of 3H-cytidine-labelled blood lymphocytes in patients with Hodgkin's disease and non-Hodgkin patients. II. Exchangeable lymphocyte pools.

The dilution in the circulating blood of lymphocytes lablled in vitro with 3H-cytidine was examined after autotransfusion in 9 patients with Hodgkin's disease (HD) stage II A-IV B, 5 of whom were untreated; in 2 untreated patients with carcinoma, and in 1 treated patient with scleroderma. The blood transit time of exchangeable lymphocytes was 37 +/- 18 min in the patients with HD and 26 +/- 6 min in the other patients. The proportion of exchangeable (recirculating) small blood lymphocytes was 39-84% in HD and 81-91% in the carcinoma patients. The relation between the size of the circulating pool of small blood lymphocytes and the total exchangeable (recirculating) lymphocyte pool was 1:20 to 1:30 in HD and 1:29 to 1:34 in the other patients. The absolute size of the recirculating pool of lymphocytes was 46-90 times 10(9) cells in HD and 100-150 times 10(9) cells in the carcinoma patients.

Adult↗

Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. I. Distribution and cellularity of the bone marrow in normal dogs.

Marrow cellularity in adult beagles (1-2 yr old) is highest in centrally located bones, with values between 8000 and 12,000 nucleated cells per sq mm. It decreases gradually towards the peripheral parts of the body, reaching values below 1000 per sq mm in bones distal to the elbow and knee. The first tail segment always contains some active marrow. The fifth segment has only stromal elements. In spongy bones fat cells appear to be distributed at random among the blood-forming elements. In the middle part of the femur the fatty marrow predominates in the center of the cylinder, while the subendosteal area is very cellular. The proximal and distal ends of the femur are more cellular than the middle. The small standard deviation of the cellularity in the spongy bones of the trunk and in the proximal and middle part of the humerus makes these sites areas of choice for quantitative studies of marrow regeneration. The large variations in cellularity of the marrow in the radius and tibia of young adult dogs make these sites unsuitable for such studies. The distribution of active and fatty marrow in dogs is similar to that of humans. The differential count of active marrow is quite constant between different dogs and in the various sites of each animal.

Animals↗

Impaired exchange of autotranfused blood lymphocytes between intra- and extravascular pools in patients with untreated chronic lymphocytic leukemia.

Autotransfusion of 3H-cytidine labeled blood lymphocytes was performed in 4 normal subjects, 3 patients with non-leukemic malignant lymphoma (1 reticulum cell sarcoma, 2 lymphosarcoma), 2 treated, non-leukemic patients with chronic lymphocytic leukemia (CLL) and 11 untreated CLL patients. Immediately after autotransfusion on the average only 41.3% and 47.5% of the infused labeled lymphocytes were recovered in the blood of the normal subjects and of the untreated CLL patients, respectively. During the first hour, in the normal subjects a higher proportion of labeled cells disappeared from the blood that in untreated CLL patients. Thereafter, this initial rapid decrease ceased and levelled off into a plateau with rather constant recovery values. At this time (1-4 hours after autotransfusion), on the average only 6.7% of the normal lymphocytes, but 27.8% of the untreated CLL lymphocytes were recovered in the blood. In the non-leukemic lymphoma of the untreated CLL lymphocytes were recovered in the blood. In the non-leukemic lymphoma patients and treated CLL patients the autotransfused lymphocytes exhibited circulation kinetics similar to those of the normal lymphocytes. The majority of blood lymphocytes from untreated patients with CLL seem to be characterized by a poor exchange rate between intra- and extravascular lymphocyte pools and a prolonged intra-vascular life span. These findings agree with the impaired recirculation kinetics of CLL lymphocytes and their abnormal 0ehaviour in several "in vitro" tests dealing with other lymphocyte functions.

Blood Transfusion, Autologous↗

Evidence for stem cell function of resting bone marrow lymphocytes identified by the complete 3H-thymidine labelling method.

Resting bone marrow lymphocytes, recongised as small lymphocytes by light microscopy, were labelled by the complete 3H-thymidine labelling technique, enriched by fractionation on a discontinuous albumin gradient and investigated for their stem cell properties by culture in diffusion chambers. Fraction 3, with the highest enrichment of labelled small lymphocytes and slight enrichment of other labelled cells (reticulum and endothelial cells), produced substantial growth, in contrast to fraction 4, with no enrichment of these cells. The number of labelled small lymphocytes per chamber in fraction 3 remained constant or tended to increase. This is assumed to be an indication of some degree of self-replication in the small lymphocyte population. Since, however, their labelling intensity decreased only slowly, it must be further concluded that part of the labelled small lymphocyte population probably remained resting. Some labelled transitional and blast cells appeared before the development of recognisable myelopoietic and erythropoietic precursors and of megakaryocytes, in agreement with the concept that small lymphocytes transfrom to transitional cells during the developmetn of normal haempopiesis.

Animals↗