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  • 1
    ISSN: 1432-0851
    Keywords: Key words Human ; T Lymphocytes ; Tumor immunity ; T cell receptors ; Gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The direct introduction of foreign genes into tumors shows promise as a therapeutic modality to enhance tumor immunogenicity. Hence, melanoma nodules were directly injected with a vector encoding an allogeneic MHC class I molecule, HLA-B7. Tumor-infiltrating lymphocytes (TIL) were isolated from cutaneous melanoma biopsies before and after HLA-B7 gene transfer. TIL were expanded in interleukin-2 (IL-2) by standard techniques for approximately 4 weeks, then analyzed for T cell receptor Vβ usage by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Prior to gene transfer, TIL Vβ usage was found to be highly restricted, the only one to four Vβ families being expressed and one or two of these families representing more than 90% of the repertoire. As anticipated, TIL Vβ usage varied among patients expressing different HLA types. However, Vβ13 was over-represented in that six of eight patients utilized Vβ13 as a dominant family, regardless of HLA type. Following HLA-B7 gene transfer, TIL Vβ usage was markedly altered: (1) Vβ families that dominated following gene transfer differed from the Vβ families utilized by TIL prior to treatment, and (2) introduction of the HLA-B7 gene resulted in a more diverse repertoire with an increase in the number of Vβ families represented. In two patients, TIL were evaluated before treatment and from multiple, distinct melanoma nodules following gene transfer. In these two patients, a comparison was made between TIL Vβ profiles obtained after treatment from nodules that had been injected with the HLA-B7 gene or left untreated. Interestingly, the Vβ repertoires of TIL from uninjected nodules following gene transfer were similar to that of TIL from injected nodules, rather than pretreatment TIL. These data demonstrate a direct immunological effect of foreign MHC gene transfer into human melanoma, and suggest that local expression of an allogeneic MHC molecule generates systemic alterations in the antitumor immune response.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of applied physiology 71 (1995), S. 559-561 
    ISSN: 1439-6327
    Keywords: Critical power ; Anaerobic work capacity ; Methodology ; Electrically-braked ergometer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examined the effect of end-point cadence on the parameters of the work-time relationship determined for cycle ergometry. Eight male subjects completed four maximal tests on an electrically-braked cycle ergometer that regulated a constant power output independent of cadence. The power outputs imposed ranged between an average of 259 W and 403 W, whereas the corresponding durations ranged between 139 s and 1691 s. During each test subjects were required to maintain a cadence of 80–90 rpm. Accumulated time to end-point cadences of 70, 60 and 50 rpm were recorded. The four work-time determinations for each of three end-point cadences were used to determine linear relationships between work and time, yielding both a y-intercept, which represents anaerobic work capacity, and a slope, which is termed critical power (CP), for each end-point cadence. There was a significant increase in the y-intercept as end-point cadence decreased from 70 to 60 rpm (F[1,7]=36.7, p 〈 0.001) or 70 to 50 rpm (F[1,7]=80.1, p 〈 0.001), but not from 60 rpm to 50 rpm (F[1,7]=3.28, p 〉 0.05). In contrast, there was no effect of end-point cadence on CP (F[2,14]=1.89, p 〈 0.05). These results demonstrate that the end-point cadence selected to terminate tests only affects the y-intercept of the work-time relationship. To control for this effect, the cadence at which each test is terminated should be standardised if determination of anaerobic work capacity, as represented by the y-intercept, is required.
    Type of Medium: Electronic Resource
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