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  • 1
    ISSN: 1573-2592
    Keywords: HIV-1 Immunogen ; antivirals ; viral load ; CD4 ; delayed-type hypersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-5655
    Keywords: Computing models ; Integrated creativity ; Technology ; Women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Women have been excluded from the mainstream development of computer hardware and software. Consequently there is an imbalance in the masculine and feminine characteristics, functioning and applications of computing. A masculine approach is encoded into the technical personality of computing, and in the skills and knowledge necessary to utilise computers. The feminine perspective broadens the scope and objectives of computing. This paper examines the current computing culture, and proposes new models for computing that embrace the methodology of creative thinking.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-4726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1434-4726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1335
    Keywords: Tumour necrosis factor α ; γ irradiation ; Interferon γ ; Ewing's sarcoma ; Peripheral primitive neuroectodermal tumour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study analyses the production of tumour necrosis factor (TNF)α and soluble TNF receptor (sTNF-R) before and after exposure to γ irradiation and interferon γ (IFNγ) in 12 cell lines derived from Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumours (pPNET). Supernatants from ES/pPNET cell cultures were tested in a TNFα-specific amplified enzyme-linked immunosorbent assay (ELISA), a bioassay, and sTNF-Rp55 and sTNF-Rp75 ELISA. The tumour cell lines released minimal amounts of TNFα, prominent amounts of sTNF-Rp55 (7/12 cell lines) and no sTNF-Rp75. Exposure to γ irradiation (5 Gy) either induced (3/12) cell lines) or up-regulated (3/12 cell lines) TNFα release without changing sTNF-Rp55 and sTNF-Rp75 levels. Priming of cultures with recombinant human IFNγ (rhIFNγ) markedly enhanced TNFα secretion in the radiation-responsive cell lines and had no influence on sTNF-Rp55 and sTNF-Rp75 levels. rhIFNγ affected the magnitude rather than the sensitivity of the radiation response. The TNFα secreted was bioactive, as shown by its cytotoxic effect of WEHI-164 cells, and neutralization of its activity by anti-TNFα monoclonal antibody. Herbimycin A (a tyrosine-specific protein kinase inhibitor) but not calphostin C (a protein kinase C inhibitor), H89 (a protein kinase A inhibitor), AACOCF3 (a specific inhibitor of phospholipase A2) and MK-886 (a specific inhibitor of 5-lipoxygenase) abrogated γ-irradiation-stimulated TNFα release. The antioxidantsN-acetylcysteine, nordihydroguaiaretic acid and mepacrine dose-dependently inhibited γ-irradiation-mediated TNFα production. Collectively our findings indicate that IFNγ priming potentiates the secretion of bioactive TNFα by ES/pPNET cells in response to γ irradiation without affecting sTNF-R release. The data suggest a requirement for protein tyrosine kinase activity and a role for reactive oxygen species in the γ-irradiation-mediated intracellular signalling pathway leading to TNFα production.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1335
    Keywords: Key words Tumour necrosis factor α  ;  γ irradiation  ;  Interferon γ  ;  Ewing's sarcoma  ;  Peripheral primitive neuroectodermal tumour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study analyses the production of tumour necrosis factor (TNF)α and soluble TNF receptor (sTNF-R) before and after exposure to γ irradiation and interferon γ (IFNγ) in 12 cell lines derived from Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumours (pPNET). Supernatants from ES/pPNET cell cultures were tested in a TNFα-specific amplified enzyme-linked immunosorbent assay (ELISA), a bioassay, and sTNF-Rp55 and sTNF-Rp75 ELISA. The tumour cell lines released minimal amounts of TNFα, prominent amounts of sTNF-Rp55 (7/12 cell lines) and no sTNF-Rp75. Exposure to γ irradiation (5 Gy) either induced (3/12) cell lines) or up-regulated (3/12 cell lines) TNFα release without changing sTNF-Rp55 and sTNF-Rp75 levels. Priming of cultures with recombinant human IFNγ (rhIFNγ) markedly enhanced TNFα secretion in the radiation-responsive cell lines and had no influence on sTNF-Rp55 and sTNF-Rp75 levels. rhIFNγ affected the magnitude rather than the sensitivity of the radiation response. The TNFα secreted was bioactive, as shown by its cytotoxic effect of WEHI-164 cells, and neutralization of its activity by anti-TNFα monoclonal antibody. Herbimycin A (a tyrosine-specific protein kinase inhibitor) but not calphostin C (a protein kinase C inhibitor), H89 (a protein kinase A inhibitor), AACOCF3 (a specific inhibitor of phospholipase A2) and MK-886 (a specific inhibitor of 5-lipoxygenase) abrogated γ-irradiation-stimulated TNFα release. The antioxidants N-acetylcysteine, nordihydroguaiaretic acid and mepacrine dose-dependently inhibited γ-irradiation-mediated TNFα production. Collectively our findings indicate that IFNγ priming potentiates the secretion of bioactive TNFα by ES/pPNET cells in response to γ irradiation without affecting sTNF-R release. The data suggest a requirement for protein tyrosine kinase activity and a role for reactive oxygen species in the γ-irradiation-mediated intracellular signalling pathway leading to TNFα production.
    Type of Medium: Electronic Resource
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