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Buse J.,TU Dresden | Dorfel D.,ChariteUniversity Medical Center Berlin | Lange H.,TU Dresden | Ehrlich S.,TU Dresden | And 2 more authors.
Cognitive Neuroscience | Year: 2015

Obsessive-compulsive disorder (OCD)-like symptoms are commonly associated with sensations of incompleteness and not-just-right experiences (NJRE). Although NJRE have gained much attention in recent years, most studies have not gone beyond a description of their phenomenology and prevalence also in healthy adults. We applied a validated harmonic expectancy violation paradigm to experimentally investigate NJRE evoked by deviant auditory perceptions. We assessed reaction times (RT) to harmonic and disharmonic chord sequences as well as their emotional appraisal in 64 healthy young adults. The participants clearly indicated disharmonic chord sequences as sounding not-just-right and incomplete and rated them as unpleasant, arousing, and irritating. The RT to disharmonic chord sequences was significantly shorter than the RT to harmonic chord sequences. This effect tended to be greater in those participants who reported stronger general experiences of incompleteness as an underlying core dimension of OCD-like symptoms. In addition, general experience of incompleteness was correlated to the difference between RT to harmonic and that to disharmonic chord sequences, indicating that the intensity of general experience of incompleteness was associated with a more readily activated processing of the deviant auditory perceptions. © 2014, © 2014 Taylor & Francis.

Braun F.K.,ChariteUniversity Medical Center Berlin | Al-Yacoub N.,ChariteUniversity Medical Center Berlin | Plotz M.,ChariteUniversity Medical Center Berlin | Mobs M.,ChariteUniversity Medical Center Berlin | And 2 more authors.
Journal of Investigative Dermatology | Year: 2012

Cutaneous T-cell lymphomas (CTCL) form a heterogeneous group of non-Hodgkin's lymphomas of the skin. In previous studies, we had characterized CTCL cells as resistant to the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which correlated to pronounced expression of the caspase-8/-10 inhibitor c-FLIP. For identification of proapoptotic strategies in CTCL cells and for overcoming their death ligand resistance, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid, sodium salicylate, and diclofenac (DF). These drugs strongly enhanced apoptosis, as well as decreased CTCL cell proliferation and vitality, and DF furthermore sensitized for TRAIL-induced apoptosis. Full activation of the caspase cascade (caspase-3,-8,-9) and decreased mitochondrial membrane potential were characteristic for NSAID treatment, whereas cytochrome c release was seen only for DF. Downregulation of Mcl-1 and enhanced surface expression of TRAIL were seen in response to NSAIDs. Most characteristic for apoptosis induction was the downregulation of c-FLIP. In agreement with the critical role of c-FLIP for apoptosis deficiency of CTCL cells, its overexpression decreased NSAID-mediated apoptosis and its downregulation by small hairpin RNA-enhanced apoptosis. The study provides a rationale for the use of NSAIDs as a new therapeutic option for CTCL patients. Supporting this concept, ex vivo lymphoma cells of CTCL patients also revealed significant sensitivity for NSAID treatment. © 2012 The Society for Investigative Dermatology.

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