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  • 1
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To define the contribution of T-lymphocyte subsets in the development of aplastic anemia (AA), T-cell subpopulations including αβT cells, γδT cells, and δTCS1-positive γδT cells, were analyzed by cytophotometry in the peripheral blood (PB) and bone marrow (BM) of patients with AA before and after 6 weeks of therapy with anti-lymphocyte globulin (ALG), methylprednisolone, and cyclosporin A (CSA). In nine patients with AA a significant decrease of PB- and BM-derived T cells was observed after 6 weeks of therapy as compared with normal controls. At diagnosis, the CD4/CD8 ratio in PB and BM of the patients did not differ from the ratio in the control population; however, a reversed ratio (〈 1) was present in PB as well as in BM after weeks of therapy. Interestingly, lymphocytes expressing the γδT-cell receptor (TCRτδ) were significantly decreased both before (PB 1.2±0.1%; BM 0.8±0.1%) and after 6 weeks of therapy (PB 0.7±0.1%; BM 0.7±0.1%) as compared with healthy controls (PB 2.4±0.2%; BM 2.3±0.2%). However, the proportion of the γδ-T-cell subpopulation expressing the δTCS1 phenotype was markedly increased before (PB 42±3.5%; BM 31±3%) and especially after 42 days of therapy (PB 77±12%; BM 45±2%) as compared with that in normal subjects (PB 19±2%; BM 9.7±0.8%). At present, follow-up is under evaluation to correlate these findings with hematological response. The pathophysiological significance of the observed alterations within the T-cell subsets and especially the γδT-cell populations will require further functional analyses, in particular since δTCS1-positive γδT cells exhibit autoimmunological capacity.
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  • 2
    ISSN: 1432-0584
    Keywords: HIV ; AIDS ; TGF-β ; TNF-α ; Hematopoietic progenitor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With progressive disease, the majority of patients with human immunodeficiency virus (HIV) infection develop bone marrow failure with anemia, leukopenia, and thrombocytopenia, the cause of which has not yet been clarified. Besides direct infection of bone marrow progenitor cells and immune-mediated cytolysis, the action of inhibitory cytokines, like transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α), has to be discussed with regard to their pathophysiological role in HIV-induced bone marrow failure. Therefore, the influence of recombinant human TGF-β and TNF-α on colony growth of pluripotent (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells from the bone marrow of HIV-1-infected persons and normal controls was assessed in methylcellulose cultures. Both cytokines inhibited the colony formation of hematopoietic progenitor cells from HIV-positive persons. When added to unseparated bone marrow cells from HIV-infected persons and normal controls, the 50% inhibition (ID50) of BFU-E by TGF-β occurred at 1.3 ng/ml and 3.7 ng/ml, respectively, while the ID50 of CFU-GM occurred at 15.5 ng/ml and 142.7 ng/ml. Concentrations of TNF-α, causing 50% inhibition of colony formation by bone marrow cells from HIV-infected or noninfected individuals were 6.3 U/ml and 17.0 U/ml for BFU-E, and 24.4 U/ml and 〉3,000 U/ml for CFU-GM, respectively. The ID50 of the CFU-GEMM growth was below the lowest concentration of both cytokines tested. The suppressive effects were specifically abolished by antibodies against TGF-β and TNF-α, thus confirming that the inhibitory activities were due to the cytokine preparation used.
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  • 3
    ISSN: 1432-0584
    Keywords: Ig rearrangement ; Adult ALL ; Oligoclonality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the configuration of the immunoglobulin genes in the leukemic blast cell DNA of 20 adults with precursor B-cell acute lymphoblastic leukemia (ALL), treated according to the BMFT protocol. Sixteen of 20 (80%) patients expressed HLA-DR antigens and lacked detectable T-cell antigens. Eleven of the 20 patients (55%) were positive for the CD10 antigen and therefore classified as common ALL. Six patients were classified by immunological phenotyping as null-ALL (30%). Three patients (15%) expressed both immature B-cell markers CD19, CD22, or CD24 and myelomonocytic markers CDw65 or CD15, suggesting precursor B-ALL with cross-lineage expression of myeloid markers. In 18 of the 20 patients (90%), rearrangements and/or deletions of the immunoglobulin heavy-chain (IgH) gene locus were found. In none of the patients was a lightchain gene rearrangement observed. Two patients (10%) had a rearrangement of one allele for the Jβ1 gene region of the TCR-β gene. In four patients (20%) more than two hybridizing bands for the IgH genes were detected. Two of these four patients with multiple hybridizing bands for the IgH genes had a t (4; 11) translocation. Two of five patients with the t (4; 11) translocation co-expressed both B-cell antigens and the myeloid antigens CD15 or CDw65. No correlation was found between the immunophenotype of the ALL and the arrangement pattern of their IgH genes. Kaplan-Meier plot analysis revealed no significant difference between adult precursor B-ALL patients with monoclonal or oligoclonal IgH gene rearrangements and their disease-free survival rates.
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  • 4
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aggressive chemotherapy of advanced myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) evolving from MDS, subacute AML and secondary AML has usually been associated with low complete remission (CR) rates, a high incidence of early death, and low disease-free survival. We therefore have initiated a phase-III trial of aggressive chemotherapy consisting of idarubicin, cytosine arabinoside, and VP-16 to improve the CR rate. Each chemotherapy cycle is followed by G-CSF to accelerate neutrophil recovery and to reduce the incidence of infections. Until now, 19 patients with high-risk AML have been entered. The CR rate is 47%, with only one death during induction. Patients achieving CR are randomized to receive either high-dose or low-dose interleukin-2 to eliminate residual leukemic cells and to prolong the duration of remission.
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  • 5
    ISSN: 1432-0584
    Keywords: Granulocyte colony-stimulating factor ; Acute lymphoblastic leukemia ; Chemotherapy ; Pilot study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5μg/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (〈0.5×109/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.
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  • 6
    ISSN: 1432-0584
    Keywords: sIL-2Receptor ; MDS ; Interleukin-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sera of ten healthy controls and of 15 patients with myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) with a cell-free enzyme-linked immunosorbent assay (ELISA). The patients with MDS underwent treatment with IL-3: eigth patients at dose levels of 250 and 500 Μg/m2 s.c. daily for 15 days, and seven patients at the dose levels of 60 and 125 Μg/m2 s.c. three times per week for 12 weeks. None of the patients had reported infectious episodes or been under treatment with cytotoxic drugs and/or cytokines within the preceding 2 months. sIL-2R levels were elevated in MDS patients compared with healthy controls (p〈0.001). sIL-2R increased in the high-dose treatment group from 504±68 U/ml to 731±199 U/ml (p〈0.025). The increased sIL2R expression in MDS could be a primary event due to involvement of lymphocytes in the malignant clone or due to a secondary alteration of the cytokine network caused by chronic neutropenia. A down-regulation of the immune response caused by neutralization of free IL-2 by sIL-2R during IL-3 therapy seems possible.
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  • 7
    ISSN: 1432-0630
    Keywords: 6855 ; 7280E ; 7340L
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Modulation doped Al0.3Ga0.7As/In x Ga1−x As/GaAs high electron mobility transistor structures for device application have been grown using molecular beam epitaxy. Initially the critical layer thickness for InAs mole fractions up to 0.5 was investigated. For InAs mole fractions up to 0.35 good agreement with theoretical considerations was observed. For higher InAs mole fractions disagreement occurred due to a strong decrease of the critical layer thickness. The carrier concentration for Al0.3Ga0.7As/In x Ga1−x As/GaAs high electron mobility transistor structures with a constant In x Ga1−x As quantum well width was investigated as a function of InAs mole fraction. If the In x Ga1−x As quantum well width is grown at the critical layer thickness the maximum carrier concentration is obtained for an InAs mole fraction of 0.37. A considerable higher carrier concentration in comparison to single-sided δ-doped structures was obtained for the structures with δ-doping on both sides of the In x Ga1−x As quantum well. Al0.3Ga0.7As/In x Ga1−x As/GaAs high electron mobility transistor structures with InAs mole fractions in the range 0–0.35 were fabricated for device application. For the presented field effect transistors best device performance was obtained for InAs mole fractions in the range 0.25–0.3. For the field effect transistors with an InAs mole fraction of 0.25 and a gate length of 0.15 μm a f T of 115 GHz was measured.
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  • 8
    ISSN: 1432-0630
    Keywords: 78.47.+p ; 78.55.Cr ; 78.45.+h
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The dependence of the bandstructure and the resulting dependences of the intensity and the wavelength of stimulated emission on the carrier density are demonstrated in optically excited Al x Ga1−x As near the crossover composition x c at room temperature. Density induced Γ to L and Γ to X crossings, based on the large band-gap renormalization near the crossover composition, are observed in samples with an AlAs mole fraction x=0.43 and x=0.46. The band crossings are indicated by strong fluctuations of the intensity and the wavelength of stimulated emission. This behavior is quantitatively well explained by using a multi-valley model for the description of the band-gap renormalization. The multi-valley model leads to an exact density-dependent prediction of the wavelength and to an estimation of the intensity of stimulated emission in indirect band-gap Al x Ga1−x As and shows the optimum AlAs mole fraction for semiconductor laser application.
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  • 9
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The electrical properties of Al0.3Ga0.7As/InxGa1−xAs modulation doped heterostructures grown on GaAs substrates were studied. We found for the normal and inverted heterostructures principal differences of the transport properties. For an InAs mole fraction of 0.2 the inverted modulation doped heterostructures show a stronger decrease in the electron mobility of the two-dimensional electron gas if the critical layer thickness of the In0.2Ga0.8As layer is exceeded, in comparison to the normal heterostructures. This behavior can be explained by the relaxation process of the In0.2Ga0.8As layer. For InxGa1−xAs heterostructures with x(approximately-greater-than)0.3 the growth mode changes from two-dimensional to three-dimensional growth, which leads to interface roughness, degrading the transport properties of the normal heterostructure. Thus for high InAs mole fractions the inverted heterostructures show better transport properties in comparison to the normal heterostructures.
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 59 (1991), S. 1102-1104 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The sensitivity of the threshold for stimulated emission on temperature is typically described by the T0 parameter of a heuristic exponential law. This T0 parameter has a value of about 80 K in AlxGa1−xAs heterostructures with a direct fundamental gap, while it is rather large (300 K) in indirect-gap AlxGa1−xAs. Samples with an AlAs mole fraction (here x=0.43 and 0.44) close to the direct-to-indirect crossover change the nature of their fundamental gap, and thus the dominant channel for stimulated emission, from indirect to direct with rising lattice temperature. This temperature-induced change in bandstructure is reflected in a drastic change of the T0 parameter. As a direct consequence of the differential T0 values, indirect-gap Al0.46Ga0.54As has a room-temperature threshold comparable to the standard laser material Al0.33Ga0.77As.
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