SummarySuccessful bacille Calmette-Guérin (BCG) immunotherapy of bladder cancer depends on the proper induction of a T helper-type 1 (Th1) immune response. In this study we investigated the possible involvement of Th1-stimulating cytokines in BCG-induced interferon (IFN)-g production as well as their potential roles in enhancing BCG-induced IFN-g from human peripheral blood mononuclear cells (PBMCs). BCG efficiently induced IFN-g production by PBMCs in a dose-dependent manner. Neutralization of endogenous cytokines interleukin (IL)-2, IL-12 and IFN-a reduced BCGinduced IFN-g by 38%, 67% and 49%, respectively. Although single recombinant (r) IL-2, rIL-12 and rIFN-a induced no or a marginal amount of IFN-g, a combination of any two or three cytokines increased IFN-g production. When BCG (a subsaturated dose) was combined with mono, dual or triple cytokines, a synergy on IFN-g production was observed. Such a synergy was readily achievable even when minimal or low doses of cytokines were used. No saturation of IFN-g production was observed even when a subsaturated BCG dose was combined with very high doses of cytokines. A robust IFN-g production was also observed when a minimal BCG dose was combined with minimal doses of triple cytokines. In addition, we demonstrated that IL-2-and IFN-a-expressing rBCGs were superior to wild-type BCG for PBMC IFN-g induction and that combination of both rBCGs showed a synergy in IFN-g production. Taken together, these results suggest that combination of BCG with certain exogenous or endogenous (expressed by rBCGs) Th1-stimulating cytokines is a rational candidate for further study in bladder cancer treatment.
We demonstrate that spectral interferometry can be used together with a well-characterized reference pulse to directly determine the spectral amplitude and spectral phase of coherent four-wave-mixing ͑FWM͒ emission from multiple quantum wells. The temporal amplitude and phase are then readily obtained by an inverse Fourier transformation. We illustrate that it is necessary to accurately determine the spectral phase, as well as the spectral amplitude, in order to correctly determine the temporal behavior. We subsequently use this technique to measure discontinuities in the temporal phase. Instabilities in the phase occur and phase jumps of ϳ are produced when both the real and imaginary parts of the FWM field are zero. These jumps occur at the minima in the quantum beats, and this condition requires the excitation of approximately equal numbers of heavy-and light-hole excitons. ͓S0163-1829͑97͒00939-9͔
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