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  • 1
    ISSN: 1573-8280
    Keywords: C-kit Ligand ; GM-CSF ; Hemopoiesis ; IL-3 ; MGF ; Myelosuppression ; Radiation ; SCF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the presence of hemopoietic cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), mast cell growth factor (MGF; also known as steel factor, stem cell factor, and c-kit ligand) has proven to be a potent hemopoietic regulatorin vitro. In these studies, we examined thein vivo effects of MGF in combination with GM-CSF or GM-CSF plus IL-3. Effects were based on the ability of these cytokines to stimulate recovery from radiation-induced hemopoietic aplasia. Female B6D2F1 mice were exposed to a sublethal 7.75-Gy dose of60Co radiation followed by subcutaneous administration of either saline, recombinant murine (rm) MGF (100Μg/kg/day), rmGM-CSF (100Μg/kg/day), rmIL-3 (100Μg/kg/day), or combinations of these cytokines on days 1–17 postirradiation. Recoveries of bone marrow and splenic spleen colony-forming units (CFU-s), granulocyte macrophage colony-forming cells (GM-CFC), and peripheral white blood cells (WBC), red blood cells (RBC) and platelets (PLT) were determined on days 14 and 17 during the postirradiation recovery period. MGF administered in combination with GM-CSF or in combination with GM-CSF plus IL-3 either produced no greater response than GM-CSF alone or down-regulated the GM-CSF-induced recovery. These results sharply contrasted results ofin vitro studies evaluating the effects of these cytokines on induction of GM-CFC colony formation from bone marrow cells obtained from normal or irradiated B6D2F1 mice, in which MGF synergized with GM-CSF or GM-CSF plus IL-3 to increase both GM-CFC colony numbers and colony size. These studies demonstrate a dichotomy between MGF-induced effectsin vivo andin vitro and emphasize that caution should be taken in attempting to predict cytokine interactionsin vivo in hemopoietically injured animals based onin vitro cytokine effects.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1619-7089
    Keywords: Immunoscintigraphy ; Technetium 99m-labelled antibodies ; CD4-specific (T-lymphocyte) antibodies ; Rheumatoid arthritis ; Localisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CD4 expressing T-lymphocytes are involved in the pathogenesis of rheumatoid arthritis, so the possibility of using radiolabelled CD4-specific antibodies to localise diseased joints was studied. Prospectively six patients with rheumatoid arthritis were investigated. Five of them received 200–300 μg of a 555 MBq technetium 99m CD4-specific antibody (MAX.16H5) and were examined with three phase bone scans. Max.16H5 (IgG1) was labelled according to the mercaptoethanol (Schwarz) method. Lymphocytes of one patient were isolated on a Ficoll-Hypaque gradient and labelled with the antibody in vitro. Scans were performed 1.5 h, 4 and 24 h post injection in anterior and posterior views. In all patients, diseased joints could be clearly imaged at as early as 1.5 h. The localisation of the diseased joints correlated (P〈0.01) with the clinical signs, with the early methylene diphosphonate (MDP) scan (P 〉 0.01) and only weakly with the late bone scan (P 〉 0.05). According to these data we conclude that99mTc-labelled CD4-specific antibodies specifically image actively diseased joints in rheumatoid arthritis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treating MRL/1pr mice, which spontaneously develop systemic lupus erythematosus and rheumatoid arthritis, with 15-DOS resulted in a decrease in the amount of autoantibodies and inhibited proteinuria of the developing glomerulonephritis with an improved survival rate of these autoimmune mice. 15-DOS treatment also lowered the percentage of animals with swollen lymph nodes and inhibited the development of splenomegaly. In the established disease 15-DOS returned urine-protein values and renal function (serum urea and creatinine) to normal levels. Circulating rheumatoid factor and autoantibodies to double-stranded DNA were reduced and the increase in paw volume (signs of a polyarthritis) was inhibited.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the therapeutic effect of 15-DOS in the two models of acute and chronic relapsing EAE in Lewis rats. In the first model adult rats developed an acute severe EAE and by day 16 all animals died. Lewis rats treated with 15-DOS showed a delayed and reduced onset of clinical symptoms and mortality was prevented. In the second model Lewis rats (aged animals) developed a chronic relapsing EAE with up to three relapses. The second and third episodes were both milder and shorter in duration. All animals treated with 15-DOS survived the delayed first attack and developed no further relapses.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The anti-ratα/β-TCR, MAb-R73 has been investigated as to its disease modifying activity on adjuvant arthritis (AA), on experimental allergic encephalomyelitis (EAE) and on a local graft versus host (GvH) reaction (popliteal lymph nodes=PLN) in Lewis or Brown-Norway rats. R73 was able to prevent the onset of the AA and even if therapy started after the establishment of AA the MAb was still able to reduce the degree of chronic inflammation and arrest its progress. Intraveneous MAb-R73 application also reduced the signs of EAE and prevented mortality. This was even seen when the substance was given after the outbreak of the clinical symptoms or when the F(ab)2 fragment of this MAb was used. Also in the model of local GvH reaction R73 acted therapeutically and lowered the PLN weights.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0584
    Keywords: Hematopoiesis ; GM-CSF ; IL-3 ; IL-1 ; Precursor cells ; Cytofluorometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Our experiments were directed towards the detection of the influence of interleukin-1 (IL-1); interleukin-3 (IL-3), and granulocyte-macrophage colonystimulating 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 CD 34+ 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 CD 34+ early precursor cells. IL-3 acted similarly and also caused an absolute decrease of CD 34+ cells in the cultures. IL-1 did not stimulate the generation of blasts or GM-CFC but elevated the number of CD 34− 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 CD 34+ early precursors. In contrast, the blast-generating and proliferation-inducing action of IL-3 is associated with a drop in the total number of CD 34+ stem cells. An efficient renewal of this population obviously depends on the presence of IL-1.
    Type of Medium: Electronic Resource
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