UVA radiation is the major component of the UV solar spectrum that reaches the earth, and the therapeutic application of UVA radiation is increasing in medicine. Analysis of the cellular effects of UVA radiation has revealed that exposure of human cells to UVA radiation at physiological doses leads to increased gene expression and that this UVA response is primarily mediated through the generation of singlet oxygen. In this study, the mechanisms by which UVA radiation induces transcriptional activation of the human intercellular adhesion molecule 1 (ICAM-1) were examined. UVA radiation was capable of inducing activation of the human ICAM-1 promoter and increasing ICAM-1 mRNA and protein expression. These UVA radiation effects were inhibited by singlet oxygen quenchers, augmented by enhancement of singlet oxygen life-time, and mimicked in unirradiated cells by a singlet oxygen-generating system. UVA radiation as well as singlet oxygen-induced ICAM-1 promoter activation required activation of the transcription factor AP-2. Accordingly, both stimuli activated AP-2, and deletion of the putative AP-2-binding site abrogated ICAM-1 promoter activation in this system. This study identified the AP-2 site as the UVA radiation-and singlet oxygen-responsive element of the human ICAM-1 gene. The capacity of UVA radiation and͞or singlet oxygen to induce human gene expression through activation of AP-2 indicates a previously unrecognized role of this transcription factor in the mammalian stress response.

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Human ICAM-expression is up-regulated by IFN-r and TNF-a and synergistically increased by a combination of both. Transient expression of ICAM-l/luciferase constructs led to definition of the regulatory regions mediating the cytokine response and showed that both are necessary for synergism. Immunochemical electromobility shift assays identified the TNF-o-dependent complexes that bound to the NF-rcB like sequence at -187 as p65/p50 and p65/c-Rel. The interferon responsive region at -75 was bound by a Statla (p91) containing complex that was activated by both IFN-y and IFN-a. Although both regions were required for synergism, no additional or enhanced binding complexes were observed.

The response of Cd(Zn)Te Schottky and resistive detectors to intense x-rays is investigated in a commercial computed tomography (CT) system to assess their potential for medical diagnostics. To describe their signal height, responsivity, signal-to-noise ratio (SNR), and detective quantum efficiency the devices are modeled as solid-state ionization chambers with spatially varying electric field and charge collection efficiency. The thicknesses and pixel areas of the discrete detector elements are 0.5-2 mm and a few mm2, respectively. The incident spectrum extends from 26 to 120 keV and comprises 10(10) quanta/s cm2. It photogenerates a carrier concentration in the semiconductor that is two to three orders of magnitude above the intrinsic concentration, but remains to a similar extent below the charge densities on the device electrodes. Stable linear operation is achieved with the Schottky-type devices under high bias. Their behavior can be modeled well if negatively charged near-midgap bulk defects with a concentration of 10(11)-10(13) cm-3 are assumed. The bulk defects explain the amount and time constant (about 100 ms) of the detrapping current measured after x-ray pulses (afterglow). To avoid screening by the trapped space charge the bias voltage should exceed 100(V) x [detector thickness/mm]2. Dark currents are of the order of the generation-recombination current, i.e., 300 pA/mm3 detector volume. With proper device design the signal height approaches the theoretical maximum of 0.2 A/W. This high responsivity, however, is not exploited in CT since the SNR is determined here by the incident quantum noise. As a consequence of the detrapping current, the response speed does not meet CT requirements. A medium-term effort for crystal growth appears necessary to achieve the required reduction of the trap density by an order of magnitude. Scintillation based detectors are, therefore, still preferred in fast operating medical diagnostic systems.

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