“Few studies have examined electrophysiological functioning in schizophrenia patients with first-rank (passivity) symptoms (FRS). In this study, we conducted a broad assessment of FRS patients’ performance using data collected as part of the Western Australia Family Study of Schizophrenia, with a focus on event-related potential (ERP) measures [P50 suppression, mismatch negativity (MMN), the Selleckchem A1331852 auditory oddball target (P300)]. and the antisaccade task. A total of 39 patients (23 patients with, and 16 patients without FRS) and 80 controls were included. The results showed that patients with FRS had significantly reduced amplitude and longer latencies on the P300, as compared
to controls. In addition, patients with FRS demonstrated more abnormalities on antisaccade error measures (error rate, self-correction latencies) relative to controls. On these measures, the performance of patients without FIRS was not significantly different from controls. P300 and antisaccade error abnormalities
in patients with FRS could not be accounted for by clinical variables, medication effects, or cognitive abilities. CA3 solubility dmso These results provide support for the proposal that FRS reflect a specific dysfunction in the monitoring and evaluation of sensory information. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Evasion of apoptosis may contribute to poor treatment response in pediatric acute lymphoblastic leukemia (ALL), calling for novel treatment strategies. Here, we report that inhibitors of apoptosis (IAPs) at subtoxic concentrations cooperate with various anticancer drugs (that is, AraC, Gemcitabine,
Cyclophosphamide, Doxorubicin, Etoposide, Vincristine and Taxol) to induce apoptosis in ALL cells in a synergistic manner as calculated by combination index and to reduce long-term clonogenic survival. Importantly, we identify RIP1 as a critical regulator of this synergism of IAP inhibitors and AraC that mediates the formation of a RIP1/FADD/caspase-8 CB-5083 research buy complex via an autocrine/paracrine loop of tumor necrosis factor-alpha (TNF alpha). Knockdown of RIP1 abolishes formation of this complex and subsequent activation of caspase-8 and -3, mitochondrial perturbations and apoptosis. Similarly, inhibition of RIP1 kinase activity by Necrostatin-1 or blockage of TNF alpha by Enbrel inhibits IAP inhibitor-and AraC-triggered interaction of RIP1, FADD and caspase-8 and apoptosis. In contrast to malignant cells, IAP inhibitors and AraC at equimolar concentrations are non-toxic to normal peripheral blood lymphocytes or mesenchymal stromal cells. Thus, our findings provide first evidence that IAP inhibitors present a promising strategy to prime childhood ALL cells for chemotherapy-induced apoptosis in a RIP1-dependent manner.