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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Graft-versus-host disease (GVHD) after allogeneic hone marrow transplantation (BMT) is initiated by immunocompetent T fells present in the graft. Selective elimination of distinct T-cell subsets or a sufficient, but not complete T-cell depletion, might abolish severe GVHD without graft rejection and loss of the anti-tumour potential. In this study we analysed the efficacy of different monoclonal antibodies (MoAb) WT32(CD3), OKT4(CD4), T101 (CDS), WT1 (CD7), and WT82 (CD8) with respect to their cytotoxicity to T cells cither as immunotoxin (IT) or in combination with complement. The cytotoxic potential was assessed by protein synthesis inhibition and clonogenic a minor effect on blood or bone marrow T cells, although they were highly inhibitory to T-cell lines. However, in the presence of 20 mm ammonium chloride, IT directed against CD3, CDS, and CD7 were highly cytotoxic. IT directed against CD4 and CD8 were less effective, due to a low internalization. The complement-mediated cytotoxicity was efficient for all antigens used.The natural killer (NK) activity, as measured by cytotoxicity to K562, was hardly depressed by anti-CD3, anti-CD4, anti-CD5, and anti-CD8, but was eliminated by ami-CD7. All procedures used had only a minimal effect on haematopoietic progenitors as measured by CFU-GM and BFU-E assays. We concluded that, although the T-cell population can be eliminated with the combination of anti-CD3, anti-CD5, and anti-CD7 antibodies plus complement, IT with 20 mm NH4CI appear to kill higher amounts of T cells- Selective elimination of CD4- and CD8-positive cells is effectively obtained by MoAb with complement.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 27 (1988), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the context of ex vivo T cell elimination from bone marrow, the anti-T cell cytotoxic potential of immunotoxins (IT) prepared by conjugation of die monoclonal antibodies (MOAb) WT32 (CD3), T101 (CD5), and WT1 (CD7) to ricin A chaw was evaluated. The cytotoxicity of IT was based on protein synthesis inhibition in human T cell lines: GHI, CEM, HPB-ALL, and Jurkat, and appeared closely related to the antigen density and internalization rate of the IT. Normal unstimulated T cells appeared to he rather insensitive to IT not due to a low antigen density or decreased internalization. The cytotoxicity of IT to T cells could he enhanced considerably by NH4Cl. Treatment of T cells with a cocktail of IT (10−8m) and 20 mm NH4Cl resulted in a 5000-fold cytoreduction as measured by clonogenic assays of limiting T cell dilutions, whereas the haematopoietic progenitor cells remained unaltered. Stimulation of T cells with phytobaemag-glutinin (PHA) prior to incubation with IT considerably increased the sensitivity to IT treatment. Thus, normal T cells are less sensitive to anti-T cell IT than T cell lines and activated T cells. This suggests that a low protein synthesis is responsible for the resistance to IT. However, a high specific cytotoxicity of IT to normal T cells can be achieved in the presence of 20 mm ammonium chloride.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Radiation and environmental biophysics 37 (1998), S. 95-100 
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Lipid peroxidation induced by heavy ion irradiation was investigated in 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) liposomes. Lipid peroxidation was induced using accelerated heavy ions that exhibit linear energy transfer (LET) values between 30 and 15 000 keV/μm and doses up to 100 kGy. With increasing LET, the formation of lipid peroxidation products such as conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances decreased. When comparing differential absorption spectra and membrane fluidity following irradiation with heavy ions and x-rays (3 Gy/min), respectively, it is obvious that there are significant differences between the influences of densely and sparsely ionizing radiation on liposomal membranes. Indications for lipid fragmentation could be detected after heavy ion irradiation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: GM-CSF ; Iododeoxyuridine Cell Cycle kinetics ; Flow cytometry ; Refractory anemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary GM-CSF administration to patients with refractory anemia (RA) induces an increase in neutrophils and eosinophils. We studied cell kinetic mechanisms underlying this observation using clonogenic assays and in vivo iododeoxyuridine labeling of bone marrow cells. Cell cycle kinetics were studied in three patients before and during GM-CSF administration (two daily subcutaneous injections of 54 or 108 Μg). No consistent effect on the relative number of bone marrow CFU-GM was noticed. The DNA synthesis time and potential doubling time of low-density bone marrow cells remained essentially the same. A slight decrease (1.5–3.7%) in labeling index was found, originating from the myelo(-mono)cytic lineage. In all three patients the release time of labeled granulocytes from the bone marrow into the peripheral blood was shortened (before GM-CSF treatment 5–7 days and during GM-CSF 3–4 days). Cell cycle kinetics of CD34+ cells were studied in order to obtain kinetic information on immature precursor and progenitor cells. The DNA synthesis time of the CD34+ cells was shortened during GM-CSF therapy, resulting in a shorter potential doubling time. GM-CSF administration to patients with RA results in a rise in granulocytes that might be due partly to an accelerated release of granulocytes from the bone marrow compartment into the circulating blood and partly to an increased proliferative activity of the immature precursor and progenitor cells.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 4 (1984), S. 687-694 
    ISSN: 1573-4935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Early changes in S-adenosylhomocysteine (SAH) hydrolase activity during DMSO-induced granulocytic differentiation of HL-80 ceils were followed. Within 24 h a decrease of activity of SAH hydrolase could be detected in induced cultures but not in control cultures. This decrease could be shown to be associated with G1 phase of the cell cycle and was detected prior to phenotypic changes of the ceils.
    Type of Medium: Electronic Resource
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