Abnormal neural oscillations in schizotypy during a visual working memory task: support for a deficient top-down network?

Neural oscillatory deficits have been proposed to be a core feature of schizophrenia spectrum disorders. In this study we aimed to confirm this by examining early evoked oscillatory patterns in the EEG theta, beta and gamma bands in individuals with high schizotypal personality trait scores. We carried out an event-related experiment using a computerised delayed matching to sample working memory (WM) task on a sample of volunteers scoring high or low on the Schizotypal Personality Questionnaire (SPQ). Phase-locking factor (PLF), a measure of network synchronisation, was reduced in the beta and gamma bands in two distinct topographical regions (fronto-central and centraloccipital). In addition, signal power in the beta band was decreased in the high schizotypy group in the same fronto-occipital network. These findings suggest that abnormalities in functional connectivity, already described in schizophrenia, extend to schizotypy. Further, the pattern and latency of the altered neural oscillations in the high schizotypy group suggests a deficient modulation of the sensory processing by higher-order structures. Such top-down deficits have been reported in schizophrenia and this data supports the idea that top-down dysfunction is a vulnerability trait that is independent of disease course, medication or symptom severity.     

The pattern of invasion of early carcinomas in Barrett's esophagus is dependent on the depth of infiltration

The differential diagnosis “high-grade intraepithelial neoplasia” or “well-differentiated Barrett's adenocarcinoma limited to the mucosa” is controversial. We investigated 277 endoscopically resected specimens of early Barrett's carcinoma. Depth of infiltration was classified as follows: m 1=carcinoma limited to Barrett's mucosa; m 2=carcinoma infiltrating the neo-muscularis mucosae; m 3=infiltration of the original lamina propria of the esophageal mucosa; m 4=infiltration of the original muscularis mucosae; sm 1, sm 2, and sm 3=infiltration into the upper third, middle third, and lower third of the submucosa. The pattern of invasion was classified and graded as follows: tubular (D 0)=only neoplastic tubuli showing cytologic criteria of malignancy – no tumor cell dissociation; dissociation grade 1 (D 1)=few dissociated tumor cells; D 2=moderate amount of dissociated tumor cells; D 3=pronounced tumor cell dissociation. 74–96% of m 1–m 4 Barrett's carcinomas limited to the mucosa have a D 0-pattern. Tubular invasion decreases only when the submucosa has been infiltrated (sm 1: 70.4%, sm 2: 30.0%, sm 3: 24.0%). Our study shows that the pattern of invasion in early cancer in Barrett's esophagus statistically significantly depends on depth of infiltration.     

Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection

The dynamics of human T-lymphotropic virus type-1 (HTLV-1) provirus expression in vivo are unknown. There is much evidence to suggest that HTLV-1 gene expression is restricted: this restricted gene expression may contribute to HTLV-1 persistence by limiting the ability of the HTLV-1-specific CD8(+) cell immune response to clear infected cells. In this study, we tested the hypothesis that derepression of HTLV-1 gene expression would allow an increase in CD8(+) cell-mediated lysis of HTLV-1-infected cells. Using histone deacetylase enzyme inhibitors (HDIs) to hyperacetylate histones and increase HTLV-1 gene expression, we found that HDIs doubled Tax expression in naturally infected lymphocytes after overnight culture. However, the rate of CD8(+) cell-mediated lysis of Tax-expressing cells ex vivo was halved. HDIs appeared to inhibit the CD8(+) cell-mediated lytic process itself, indicating a role for the microtubule-associated HDAC6 enzyme. These observations indicate that HDIs may reduce the efficiency of cytotoxic T-cell (CTL) surveillance of HTLV-1 in vivo. The impact of HDIs on HTLV-1 proviral load in vivo cannot be accurately predicted because of the widespread effects of these drugs on cellular processes; we therefore recommend caution in the use of HDIs in nonmalignant cases of HTLV-1 infection.