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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Insertion of various cDN As in the genome of the vaccinia virus (VV) enables the in vivo and in vitro study of the functional role and/or the immunogenicity of the virally encoded recombinant proteins. We have prepared a recombinant VV expressing the cDNA of the human cytokine HILDA/LTF (human interleukin for DA cells/leukaemia inhibitory factor), and used this virus to immunize mice against this protein, which is very homologous to its murine counterpart (∼80% homology). We also constructed and expressed by the same system a chimeric gene encoding the HILDA/LIF protein fused to the 37 COOH-terminal amino-acids of the human decay accelerating factor (DAF). This sequence proved to be sufficient for the targeting of the fusion protein to the cell membrane, where it is linked to the phosphatidylinositols. Both recombinant VVs induced cytokine-specific antibodies in mice as analysed with an FLISA where the recombinant HILDA/LIF was plastic-coated and a cytofluorometric assay where the LIF-DAF molecule was present at the cell surface of stably transfected PS15. In the latter case HILDA/LIF remained biologically active suggesting that it was expressed in its native form. The LIF-DAF fusion protein was found to exhibit a better capacity to elicit an antibody response against the native form of the cytokine as detected in cytofluorometric assays. Whatever the recombinant virus used to immunize the mice, the MoAbs obtained were positive either in the ELISA or in the cytofluorometric assays but one, which suggested that the plastic coating induced a conformationa1 change of HILDA/LIF.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1238
    Keywords: Key words Acute respiratory distress syndrome ; Leukaemia inhibitory factor ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine integrated in cytokine networks and its concentration has been shown to be elevated in bronchoalveolar lavage fluid of patients with the acute respiratory distress syndrome (ARDS). The aim of our study was to evaluate the production of LIF by culturing blood cells from patients with ARDS. Patients: 8 patients with ARDS, 8 patients with pneumonia and 5 healthy subjects. Measurements and results: The blood samples were taken on day 1 after onset of ARDS. LIF was measured, in the cell-free supernatant, with an enzyme-linked immunosorbent assay after 24 h, 48 h and 72 h of blood cell culture. LIF was detectable in some patients in the ARDS group: at i) at 24 h and 48 h: in 2 patients ii) at 72 h in 4/5 patients (140 ± 231 pg/ml). Only in the 4 patients in whom LIF was measured at 72 h was ARDS associated with the multiple organ dysfunction syndrome. Furthermore, among the 5 patients with ARDS who subsequently died, 4 had a detectable LIF. Conclusions: We have observed that LIF was produced only in ARDS, but not in all patients. The production of LIF seems to be a good indicator of the severity of ARDS. These preliminary results must be confirmed by a larger study.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2277
    Keywords: Cyclosporin A monotherapy in kidney transplantation ; Azathioprine in kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A controlled trial was carried out in 78 kidney transplant recipients under cyclosporin A (CyA) monotherapy who had experienced a first rejection episode. Thirty-nine were randomly selected to receive azathioprine (AZA; 2 mg/kg per day) in combination with CyA (group AZA+), while the others continued to receive CyA alone (group AZA−). Four of the patients in the study died; three were in group AZA+ and the cause of their deaths was cardiovascular. Graft survival rates were 97% at 6, 12, and 24 months postrejection in group AZA+ as compared to 97%, 90%, and 81%, respectively, in group AZA− (P〈0.05 at 12 and 24 months). Significantly more patients were free of rejection with the double therapy than with CyA monotherapy (75% vs 51% at 12 months;P〈0.05). In spite of the addition of a second immunosuppressive drug, the CyA dosages given and the CyA trough blood levels maintained were similar in the two groups. Serum creatinine was similar in patients with and without AZA. Infectious complications were also similar in both groups. A significant macrocytosis was the only side effect of AZA therapy. On the whole, these data show the benefit of CyA-AZA double therapy in the prevention of rejection recurrence without exposing patients to either increased risk of infection or serious side effects of AZA. Whether this double therapy should be systematically administered to all recipients or only after a first rejection episode is discussed.
    Type of Medium: Electronic Resource
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