Biomedical subjects

M Schumm

Publications and source records attributed to M Schumm.

40 records · Page 3Linked to original sources

PubMedDate not supplied

A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients: preliminary results of a pilot study.

Transplantation of hematopoietic stem cells from mismatched related donors makes a potential donor available for every child in need of stem cell transplantation. Here, we compare three different graft manipulation methods in patients with leukemias and lymphomas: positive selection of stem cells with either CD34 (n = 39) or CD133-coated magnetic microbeads (n = 14) and a new strategy which depletes T- and B-cells through the use of CD3- and CD19-coated microbeads (n = 11). Median purity of stem cells was comparable after CD34 (+)-selection and CD133 (+)-selection, whereas stem cells were only slightly enriched after CD3 (+)/CD19 (+)-depletion (97.5 %, 93.4 % and 1.02 %). Indirect depletion of T-cells by positive selection resulted in 1 x 10 (4) (median) residual CD3 (+)-cells/kg (0.7-3 x 10 (4)). Patients with CD3/CD19-depleted grafts received 3.2 x 10 (4) (median) (0.7-16 x 10 (4)) residual T-cells/kg. Those grafts also comprised NK-cells (median number: 86 x 10 (6)/kg), dendritic cells and monocytes/granulocytes. Primary engraftment of the stem cell products was comparable after CD34- and CD133-selection (85 and 72 %). In the CD3/CD19 group, 91 % had a primary engraftment. After reconditioning, all patients (64/64) were finally engrafted. Patients with CD34-selected or CD133-selected grafts had similar incidences of a GvHD II-IV (3 and 7 %), whereas a GvHD was slightly increased in patients receiving CD3/CD19-depleted cells (27 %). Reconstitution of CD3 (+) T-cells was faster in the CD3/CD19 group than in the CD34 or CD133 group. These preliminary results indicate, that CD3/CD19-selected grafts may be advantageous regarding engraftment and immunoreconstitution. Since effector cell with potential antileukemic activity are cotransfused, such grafts may be suited in particular for patients with insufficient remission.

AC133 Antigen↗

PubMedDate not supplied

Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects.

Pediatric patients with relapsed metastatic tumors have a poor prognosis and new treatment strategies are warranted. We present preliminary results of a pilot study, evaluating the feasibility and toxicity of transplantation of haploidentical T and B cell depleted grafts with high numbers of NK cells. 6 patients with relapsed metastatic neuroblastomas (n = 4), rhabdomyosarcoma (n = 1) or Ewing's sarcoma (n = 1) after previous autologous transplantation received CD3/CD19 depleted grafts from mismatched family donors with a median number of 16 x 10 (6)/kg stem cells, 167 x 10 (6)/kg Natural Killer cells and only 5.4 x 10 (4)/kg residual T cells. A melphalan-based, reduced intensity conditioning was used. Despite pretransplant chemotherapy, patients entered transplantation with significant tumor burden. Primary engraftment occurred in 6/6 patients. One patient had secondary graft failure. Hematopoietic recovery was rapid (ANC > 0.5 x 10 (9)/L: 11 days (9-12); independence from platelet substitution: 8 days (7-11)). Four patients had acute GvHD grade II, limited chronic GvHD was observed in 2 patients. No transplant-related mortality and only low toxicity occurred. Four patients died from progression, two patients are alive. Overall median survival time is 6 months (2-11) to date. Analysis of posttransplant NK cell function revealed stable cytotoxic activity against K562 targets, whereas activity against neuroblastoma targets was low. Stimulation with cytokines and use of appropriate antibodies clearly enhanced specific lysis in vitro. In summary, these preliminary results indicate the feasibility and low toxicity even in intensively pre-treated patients with neuroblastomas/sarcomas. This approach may form the basis for posttransplant immunomodulation and other therapeutic strategies. Further experience is warranted to evaluate the method.

Acute Disease↗

PubMedDate not supplied

Simulation of complex movements using artificial neural networks.

A simulated network for controlling a six-legged, insect-like walking system is proposed. The network contains internal recurrent connections, but important recurrent connections utilize the loop through the environment. This approach leads to a subnet for controlling the three joints of a leg during its swing which is arguably the simplest possible solution. The task for the stance subnet appears more difficult because the movements of a larger and varying number of joints (9-18: three for each leg in stance) have to be controlled such that each leg contributes efficiently to support and propulsion and legs do not work at cross purposes. Already inherently non-linear, this task is further complicated by four factors: 1) the combination of legs in stance varies continuously. 2) during curve walking, legs must move at different speeds, 3) on compliant substrates, the speed of the individual legs may vary unpredictably, and 4) the geometry of the system may vary through growth and injury or due to non-rigid suspension of the joints. This task appears to require some kind of "motor intelligence". We show that an extremely decentralized, simple controller, based on a combination of negative and positive feedback at the joint level, copes with all these problems by exploiting the physical properties of the system.

Animals↗

PubMedDate not supplied

Spontaneous tumor cell cytotoxicity mediated by peripheral blood mononuclear leukocytes of the dog.

Peripheral blood samples from 37 dogs of different breeds were separated into mononuclear leukocytes, strongly plastic adherent cells, plastic nonadherent cells, nylon wool nonadherent lymphocytes (NAL), Percoll density gradient enriched lymphocyte fractions and monoclonal antibody M-T606-negative cells. The inherent ability of each cell fraction to exert spontaneous cell-mediated cytotoxicity (SCMC) was tested in an 18-hour chromium release assay using two allogeneic and one xenogeneic tumor cell line(s) as the targets. Among the lymphocytes enriched by Percoll density gradient centrifugation natural killer cells could be clearly identified due to their morphology (large granular lymphocytes) and increased cytotoxic potency. Even high SCMC was mediated by effector cell populations showing plastic or nylon wool adherence and a high proportion of peroxidase-positive cells. Immunomagnetic selection of monoclonal antibody M-T606-nonreactive canine NAL regularly resulted in a strong increase in cytotoxicity mediated by M-T606- cells. Cytotoxic activity was found in cell-free supernatants from effector:target cell mixtures indicating the release of soluble leukolysins.

Animals↗