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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We investigated if dendritic cells (DCs) were able to present intracellularly located antigens derived from apoptotic cells to T cells, thereby inducing a CD4+ and a CD8+ response. A transfected cell line with the cytomegalovirus-derived protein pp65 was triggered to go into apoptosis by ultraviolet B (UVB) irradiation, and after the uptake of apoptotic cells by DC, the activation and proliferation of T cells were determined. We found that DC efficiently phagocytosed apoptotic cells and induced a CD4+ and a CD8+ T-cell response specific for the viral protein pp65. This mechanism can be useful for vaccination studies to induce an antiviral immune response.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Key words CYP2D6 ; CYP2C19 ; Dutch population
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We examined a large database containing results on CYP2D6 and CYP2C19 activity of 4301 Dutch volunteers phenotyped in the context of various clinical pharmacology studies. Methods: The subjects were given 22 mg dextromethorphan, 100 mg mephenytoin and 200 mg caffeine. For CYP2D6, the dextromethorphan/dextrorphan metabolic ratios in urine samples taken for a subsequent 8 h were used. Dextromethorphan and dextrorphan were quantified by reversed-phase high performance liquid chromatography. For CYP2C19 similarly obtained (R)-mephenytoin and (S)-mephenytoin ratios were used. (S)-mephenytoin and (R)-mephenytoin were analysed and quantified by enantioselective capillary gas chromatography. In addition, CYP2C19 poor metabolizer (PM) subjects were reanalysed after acidic pre-treatment of urine samples to confirm the PM status. Results: The investigated population mainly comprised Caucasian (98.9%) males (68%). The age ranged from 18 to 82 years. For CYP2D6, it was found that 8.0% of the subjects were PMs. The average metabolic ratio was 0.014 (0.033) for subjects who showed extensive metabolizing activity (EM) and 5.4 (7.6) for PM subjects. For CYP2C19, it was found that 1.8% of the subjects were PMs. The metabolic ratio was 0.162 (0.124) for EM subjects and 1.076 (0.040) for PM subjects. Within the EM group the metabolic ratio in females was significantly lower for CYP2D6 (−20%) and significantly higher for CYP2C19 (+40%) compared with males. For PMs there was no such difference for CYP2D6 (P = 0.79) or CYP2C19 (P = 0.20). Oral contraceptive (OC) use significantly decreased the CYP2C19 activity by 68% for mephenytoin as compared to non-OC using females. Conclusions: For CYP2D6, the PM incidence (8.0%) is in accordance with literature data. The CYP2C19, PM incidence (1.8%) is low compared to reports from other European countries. For mephenytoin, the acidification procedure has been shown to be very important for the confirmation of CYP2C19 PMs. In EM females compared to EM males, CYP2D6 activity is increased and CYP2C19 activity is reduced. For CYP2C19 in particular this reduction is substantial and most pronounced in the age range from 18 to 40 years. For CYP2C19, the reduced activity is associated with the use of oral contraceptives.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 41 (1998), S. 202-210 
    ISSN: 0021-9304
    Keywords: IFN-γ ; macrophages ; giant cells ; inflammatory reactions ; biomaterials ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Biomaterials are increasingly used for clinical applications. However, loss of function may occur owing to tissue reactions, which are mainly caused by a variety of inflammatory reactions. Recently, we demonstrated that macrophages (MØ) and T cells play key roles in these reactions. Since immunological studies showed that the T cell-derived cytokine interferon-γ (IFN-γ) activates MØ, the aim of this study was to investigate the possibility of modulating tissue reactions to biodegradable biomaterials by inactivating IFN-γ. Dermal sheep collagen (DSC) was used as a test biomaterial. DSC impregnated with anti-IFN-γ or phosphate-buffered saline (control) was implanted in rats. The results showed that cellular ingrowth and formation and function of giant cells were strongly delayed by anti-IFN-γ. Also, MHC class II expression was strongly inhibited. In the treated DSC, some huge giant cells were formed at the interface but association with the DSC bundles did not occur. Finally, in both the control and treated DSC, T cells and NK cells were rarely detected. This study demonstrates that IFN-γ plays an important role in the inflammatory reaction to biomaterials. This reaction can be modulated by anti-IFN-γ, which warrants further studies of anti-IFN-γ for clinical application to prevent unwanted tissue reactions to biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 202-210, 1998.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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