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Biomedical subjects

M Wächter

Publications and source records attributed to M Wächter.

15 recordsLinked to original sources

Safety improvement issues for mission aborts of future space transportation systems.

Two-stage winged space access vehicles consisting of a carrier stage with airbreathing turbo/ram jet engines and a rocket propelled orbital stage which may significantly reduce space transport costs and have additional advantages offer a great potential for mission safety improvements. Formulating the nominal mission and abort scenarios caused by engine malfunctions as an optimal control problem allows full exploitation of safety capabilities. The shaping of the nominal mission has a significant impact on the prospective safety. For this purpose, most relevant mission aborts are considered together with the nominal mission, treating them as an optimization problem of branched trajectories where the branching point is not fixed. The applied procedure yields a safety improved nominal trajectory, showing the feasibility of the included mission aborts with minimum payload penalty. The other mission aborts can be separately treated, with the initial condition given by the state of the nominal trajectory at the time when a failure occurs. A mission abort plan is set up, covering all emergency scenarios.

Journal Article↗

C/EBPepsilon -/- mice: increased rate of myeloid proliferation and apoptosis.

CCAAT/enhancer binding protein epsilon (C/EBPepsilon) is essential for terminal granulocytic differentiation. Its expression begins at the transition between the proliferative and non-proliferative compartments of myelopoiesis. We studied the effect of targeted disruption of the C/EBPepsilon gene on murine myeloid proliferation and apoptosis. Bone marrow cellularity of C/EBPepsilon -/- and wild-type mice was 95% and 65%, respectively. The C/EBPepsilon -/- mice had an expansion in the number of their CFU-GM/femur. The number of myeloid committed progenitor cells in the peripheral blood and the spleen of these mice was also increased. Bromodeoxyuridine (BrDU) pulse labeling studies demonstrated that the fraction of actively proliferating cells was two-fold higher in the bone marrow of C/EBPepsilon -/- mice. However, the number of myeloid colonies arising from purified Sca-1+/lin- early hematopoietic progenitor cells and from bone marrow mononuclear cells grown in different cytokine combinations was not significantly different between wild-type and knock-out mice. Also, long-term marrow growth, and CFU were not different between the wild-type and C/EBPepsilon -/- mice. The sensitivity to induction of apoptosis in the committed progenitor cell compartment after either withdrawal of growth factor or brief exposure to etoposide was normal. However, Gr-1 antigen-positive C/EBPepsilon -/- granulocytic cells showed an increased rate of apoptosis in comparison to their wild-type counterparts. In summary, the myeloid compartment appears to be expanded in mice lacking C/EBPepsilon. However, this is not the consequence of an intrinsic myeloproliferation but due to an indirect, possibly cytokine-mediated stimulation of myelopoiesis in vivo. C/EBPepsilon may have a role in the inhibition of apoptosis in maturing granulocytic cells.

Animals↗

New EU regulations in endoscopy.

As a result of European unification, new regulations valid within the territory of the European Union (EU) have been negotiated and published. As in other medical fields, the Medical Device Directive (MDD) is the most important new regulation and also effects endoscopy. In a transition period until June 1998, the MDD will be transposed into national law by the member states of the EU. Compliance with the MDD and other European regulations is indicated by the CE mark affixed to the product.

Endoscopes↗

Comparative analysis of the influences of IL-1, IL-3 and GM-CSF on the commitment of granulocyte-macrophage progenitors in vitro.

Our experiments were directed towards the detection of the influence of interleukin-1 (IL-1); interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the generation of granulocyte-macrophage progenitor cells. We also set out to examine whether this process is connected with changes within the early precursor cell compartment. Bone marrow suspension cultures (12 days) supplemented with these cytokines were tested for the presence of GM colony-forming cells (GM-CFC) in a colony-forming unit assay. The percentage of CD34+ and HLA-DR+ as well as the number of blasts and promyelocytes were estimated cytofluorometrically and morphologically. The proliferative effect of GM-CSF was associated with a net increase of GM-CFC and HLA-DR+ myeloid cells and a decrease in the percentage of CD34+ early precursor cells. IL-3 acted similarly and also caused an absolute decrease of CD34+ cells in the cultures. IL-1 did not stimulate the generation of blasts or GM-CFC but elevated the number of CD34- as well as HLA-DR-expressing cells in the cultures. These results imply that GM-CSF supported the maintenance of hematopoiesis in vitro. The transition from early precursor cells to committed myeloid progenitor cells (GM-CFC) and more mature precursor cells (G-CFC, M-CFC) may be supported by GM-CSF without affecting the self-renewing capacity of CD34+ early precursors. In contrast, the blast-generating and proliferation-inducing action of IL-3 is associated with a drop in the total number of CD34+ stem cells. An efficient renewal of this population obviously depends on the presence of IL-1.

Antigens, CD↗

Cytofluorometric and cytomorphologic analysis of human bone marrow cells derived from stromal cultures stimulated by granulocyte-macrophage colony-stimulating factor, interferon-gamma and splenopentin pentapeptide.

We studied the influence of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF), human recombinant interferon-gamma (hrIFN-gamma) and splenopentin pentapeptide (Sp-5), either alone or in combination, on the proliferation and differentiation of human bone marrow cells in modified Dexter's cultures. After 10, 14 and 21 days cells were analyzed by classical staining according to Pappenheim and by cytofluorometry with a set of different monoclonal antibodies. IFN-gamma inhibited the proliferation of progenitor cells and provided signals promoting monocytic differentiation, whereas GM-CSF induced the proliferation of blastoid elements which expressed HLA-DR and M2 (VIM-2 monoclonal antibody), but progressively lost surface CD34. Furthermore, an increase of CD15+ cells was also observed. When GM-CSF was tested in combination with IFN-gamma, it abolished the inhibitory effect of IFN-gamma and both cytokines synergized to promote the expression of CD11c, CD14 and M2 surface antigens. Sp-5 alone had only a marginal activity, but it potentiated the effects of GM-CSF. These findings suggest that GM-CSF may induce the transition from stem cells to committed myeloid progenitors. In contrast to IFN-gamma, Sp-5 can serve as an additional proliferative signal with negligible effects on cell maturation.

Amino Acid Sequence↗

Influence of cryopreservation on human leukaemic clonogenic cells (CFU-L).

The biological and clinical significance of growth characteristics of leukaemic clonogenic cells (CFU-L) cultured from patients has been the subject of many studies. While some investigators collect leukaemic cells in large numbers from blood of untreated patients and store them in a frozen state before use in experiment, others study fresh cells. Since cryopreservation may alter the proliferation and differentiation of CFU-L, we have followed its influence and that of DMSO, used as protective agent and known to be an inducer of differentiation in leukaemic blasts, on the clonogenicity of peripheral blast cells from patients with AML and CML in blast crisis. Our data show that a short incubation with 7.5% DMSO (with or without cryopreservation) induced increase in the clonogenicity and proliferation rate of CFU-L (without morphological changes). The possible causes of these effects as well as the question of aggressivity of leukaemic blasts after the short incubation with 7.5% DMSO are discussed.

Blast Crisis↗

Bone marrow stromal culture from patients with myelodysplastic syndromes and patients at different stages of acute nonlymphocytic leukaemia.

The haematopoietic microenvironment or stroma plays a decisive role for the proliferation and differentiation of haemopoietic cells. We studied if bone marrow cells from patients with myelodysplastic syndromes (MDS) and acute nonlymphocytic leukaemias (ANLL) are altered in their ability to form adherent stromal layer with active haemopoiesis in the Dexter liquid culture. Bone marrow cells were obtained from 24 normal volunteers, 28 patients with ANLL in different stages of the disease and 9 patients with MDS. There are no differences between the stromal layers of patients with ANLL in complete remission and those of normal volunteers after two weeks of cultivation. However, bone marrow cells from patients with ANLL before treatment and from patients in relapse formed a poor adherent stromal layer in most cases. In 6 of 9 cases we found the normal stromal grade of bone marrow cells from patients with MDS. There were qualitative differences in the nonadherent cell population between normal and ANLL patients in complete remission. In most cases we found morphologically recognizable erythroid cells after two-weeks Dexter liquid culture of bone marrow cells from patients with ANLL in complete remission, which were not seen with normal volunteers. This could be an indication of harmful effects on the balance of haematopoiesis caused by previous infiltration with leukaemic cells or/and high-dose chemotherapy.

Bone Marrow Cells↗

[Effect of cytosine arabinoside on the differentiation of granulocyte-monocyte progenitors (CFU-GM) and myeloid leukemia blasts (CFU-L) in vitro].

The serum concentrations of Ara-C are in the range from 10(-6) to 10(-8) M in LD-Ara-C treated patients. The growth of CFU-GM from bone marrow of healthy volunteers was depressed depending on Ara-C-concentration applied in vitro. The growth of CFU-L from peripheral blood of two patients with AML (M 2) and one patient with CML in blast crisis was differently influenced by Ara-C-application in vitro. An elevated proportion of mature cells was observed in smears of cultured cells with Ara-C from two patients. The usefulness of Ara-C for a differentiation inducing therapy is discussed.

Cell Differentiation↗

[Determination of the S-phase fraction of myeloid-determined stem cells (CFU-GM) using the cytosine arabinoside suicide technic in patients with acute myeloid leukemia in complete remission following polychemotherapy].

S-phase fraction of granulocyte-macrophage colony forming cells (CFU-GM) was assessed by cytosine arabinoside suicide technique in five normal volunteers and eight patients with acute myeloblastic leukaemia in complete remission after the cessation of polychemotherapy. An increased proliferation of CFU-GM (S-phase-fraction: 55-80%) was found in bone marrow of patient in complete remission up to the 27th day after polychemotherapy. Reduction of this increased proliferation was seen at day 30 after the cessation of polychemotherapy (S-phase fraction: 22 and 33%). Because of increased proliferation of CFU-GM in the early phase after polychemotherapy cytostatic drugs of the antimetabolite-type seem to be unsuitable for purging bone marrow in remission.

Adolescent↗

Contribution to the contamination problem in transmission electron microscopy.

The contamination of different supporting films is measured by irradiating a circular area of a few micron diameter and by using an electron probe of a few ten nm diameter. Contamination rings are generated by this method. They can be explained by diffusion of the hydrocarbon molecules on the specimen surface and by adsorption from the vacuum. The influence of specimen heating and charging are discussed. Some specimen cleaning methods have been examined. The best results were obtained by immersion of the specimen and the cartridge in methanol.

Hot Temperature↗