Retinoic acid and vitamin E modulate expression and release of CD178 in carcinoma cells: consequences for induction of apoptosis in CD95-sensitive cells.

CD178 (CD95-ligand) is expressed on several tumor cells and likely influences the interaction of the tumor with the host immune system. However, little is known about the mechanisms that regulate its expression on the cell surface. We have evaluated the ability of various compounds and cytokines to regulate cell surface expression and release of soluble CD178 in various carcinoma cell lines. Vitamin E succinate (VES) and retinoic acid (RA) were found to reduce CD178 surface expression, whereas interferon-gamma stimulated a slight upregulation. At 48 h, the regulation of surface CD178 by VES and RA arose from a small decrease in CD178 mRNA and to a greater extent due to an increase in the release of soluble CD178; the latter was blocked by addition of a metalloproteinase inhibitor. Accordingly, VES and RA treatment diminished the ability of tumor cells to kill CD95-sensitive cells and this effect was markedly reduced by the presence of a metalloproteinase inhibitor. Our results indicate that, in vitro, CD178 expression on the cell surface of tumor cells can be regulated by agents that alter both expression and release of the ligand. In vivo, such treatments may play an important role in the outcome of tumor sensitivity or resistance to host immune mechanisms.

Hypermetabolism in the ventrolateral thalamus in unilateral Parkinsonian resting tremor: a positron emission tomography study.

Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral network including the thalamus. An imaging study was performed on eight PD patients with strictly unilateral resting tremor using fluorodeoxyglucose positron emission tomography coregistered to 3-dimensional magnetic resonance imaging. Increased metabolic activity of high statistical significance (P<0.001) was found in the anterior ventrolateral nuclear group of the thalamus located contralateral to the tremor side. The metabolic changes significantly covaried with tremor amplitudes. For the first time, it could be demonstrated that thalamic metabolic changes associated with tremor in PD are localized in the ventral lateral anterior nucleus (VLa). The results are discussed with respect to previous studies on tremor generation.

Cortical activation evoked by visual mental imagery as measured by fMRI.

One of the major controversies in cognitive neuroscience is whether the primary visual cortex and nearby areas are involved in visual mental imagery. In an fMRI study we examined the brain activity of 10 healthy subjects under different task conditions: in the perception condition subjects saw complex geometrical shapes and had to decide whether other highlighted stimuli fell inside or outside the figure. In the imagery condition subjects saw only the highlighted stimuli and were instructed to imagine the previously studied geometrical shapes to solve the same task. Although the behavioral data show a distance effect that would be expected based on topographically organized mental images, the functional imaging data do not show increased activity in the primary visual cortex in the imagery condition. In the occipital cortex a slightly increased activity was found only in the visual association cortex (BA 19), whereas the highest activation was observed in the parietal cortex (BA 7 and 40). The results of the study do not support the assumption that the primary visual cortex is involved in visual mental imagery, but rather that a network of spatial subsystems and higher visual areas appears to be involved.