The immune response is thought to play a role in dysregulating epithelial growth in cholesteatoma of the middle ear. Through immunohistochemistry (using 18 monoclonal antibodies) on 10 specimens from human middle ear cholesteatomas, T-helper cells mixed with plasma cells, macrophages and scattered T-suppressor and B cells, have been detected in the perimatrix. Mast cells have also been identified in the perimatrix, usually close to the epithelium. Elements positive for D-related human leukocyte antigens (HLA-DR) were more than half of the immune cells. The endothelium of the perimatrix showed a sharp reactivity to the intercellular adhesion molecule-1 (ICAM1) and to the endothelial derived leukocyte adhesion molecule-1 (ELAM1), which play a role in recluting inflammatory cells and modulating the immune response. The expression of ICAM1 in the basal layer of the matrix indicates the homing of inflammatory reactions at the epithelial-stromal junction of the cholesteatoma. An intense expression of interferon-gamma receptor (IFN gamma R) was found in the basal layers of the cholesteatoma matrix, and overexpression of the epithelial growth factor receptor (EGFR) was found in all layers of the matrix. These data support the hypothesis that the epithelial cells in middle ear cholesteatoma are in an activated state and that their hyperproliferation is mediated through cytokines and adhesion molecules.
Pavlovian conditioning holds the potential to incentivize environmental cues, leading to approach behavior toward them, even outside our awareness. Animal models suggest that this is particularly true for the so-called sign-tracker (ST) phenotype, which is considered to reflect a predisposition toward developing addiction-related behaviours. Despite its potential clinical relevance, few studies have demonstrated the translational validity of this model, likely due to difficulties in studying Pavlovian processes in humans. To fill this gap, we combined an ecological momentary assessment with ambulatory peripheral autonomic monitoring to test the hypothesis that traits associated with ST in preclinical studies would be associated with attribution of high incentive salience to reward-related cues. Several times for 2 days, participants were asked to rate the attractiveness of several preselected ecological rewards (e.g., coffee) and the preceding cues (the smell of coffee) while their electrocardiogram was recorded. While no absolute difference in subjective and physiological measures of motivational approach to daily cues compared with rewards emerged, individuals with high levels of impulsivity, obsessive-compulsive, and addiction-prone behaviors rated as more attractive and showed a greater increase in sympathetic arousal to cues versus rewards. The opposite pattern emerged for those with low levels in those dispositional traits, who responded more (both subjectively and physiologically) to rewards compared with their preceding cues. This study represents an attempt to answer the call to parcel complex behaviors into smaller constructs, improving the early detection of those who are vulnerable to develop psychopathological disorders, particularly in the domain of impulse control such as addiction.
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