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Helmut R Salih

Publications and source records attributed to Helmut R Salih.

3 recordsLinked to original sources

Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding.

The immunoreceptor NKG2D stimulates tumor immunity through activation of CD8 T cells and NK cells. Its ligand MICA has been shown to be broadly expressed on human tumors of epithelial origin. MICA expression correlates with an enrichment of Vdelta1 T cells in tumor tissue. We report that human tumor cells spontaneously release a soluble form of MICA encompassing the three extracellular domains, which is present at high levels in sera of patients with gastrointestinal malignancies, but not in healthy donors. Release of MICA from tumor cells is blocked by inhibition of metalloproteinases, concomitantly causing accumulation of MICA on the cell surface. Shedding of MICA by tumor cells may modulate NKG2D-mediated tumor immune surveillance. In addition, determination of soluble MICA levels may be implemented as an immunological diagnostic marker in patients with epithelial malignancies.

Animals↗

Spatial imagery in deductive reasoning: a functional MRI study.

Various cognitive theories aim to explain human deductive reasoning: (1) mental logic theories claim syntactic language-based proofs of derivation, (2) the mental model theory proposes cognitive processes of constructing and manipulating spatially organized mental models, and (3) imagery theories postulate that such abilities are based on visual mental images. To explore the neural substrates of human deductive reasoning, we examined BOLD (blood oxygen level dependent) contrasts of twelve healthy participants during relational and conditional reasoning with whole-brain functional magnetic resonance imaging (fMRI). The results indicate that, in the absence of any correlated visual input, reasoning activated an occipitoparietal-frontal network, including parts of the prefrontal cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior and inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual association cortex (BA 19). In the discussion, we first focus on the activated occipito-parietal pathway that is well known to be involved in spatial perception and spatial working memory. Second, we briefly relate the activation in the prefrontal cortical areas and in the anterior cingulate gyrus to other imaging studies on higher cognitive functions. Finally, we draw some general conclusions and argue that reasoners envisage and inspect spatially organized mental models to solve deductive inference problems.

Adult↗

Differentiation of promyelocytic leukaemia: alterations in Fas (CD95/Apo-1) and Fas ligand (CD178) expression.

The survival of leukaemic blasts contributes to the pathological mechanism of acute promyelocytic leukaemia (APL). While treatment of APL using retinoic acid (RA) is a model of differentiation therapy, little is known about possible effects of this treatment on the Fas/FasL system. Investigation of APL cells from patients undergoing differentiation therapy with RA and of promyelocytic HL-60 and monoblastic U-937 cells cultured with RA revealed a reduction of surface expression of both Fas and its ligand. Accordingly, the sensitivity of the cells to anti-Fas-induced apoptosis decreased proportionally and the reduced expression of FasL resulted in a decreased ability of the leukaemic cells to induce apoptosis in T cells. Our findings demonstrate that there are significant changes in Fas and FasL expression during RA treatment of APL, which probably have consequences for the interaction between host immune and leukaemia cells, and thus may be involved in the beneficial effects of differentiation therapy.

Antineoplastic Agents↗