No abstract

No abstract

Several lines of evidence implicate aberrant glutamate neurotransmission in the pathophysiology of schizophrenia. In particular, compromised signaling through the N-methyl-D-aspartate (NMDA) receptor has been linked to positive, negative, and cognitive symptoms of this illness. Studies in postmortem brain have identified altered expression of several structural and signaling molecules of the postsynaptic density (PSD), including the abundantly expressed protein PSD-95, which binds directly to NR2 subunits of the NMDA receptor and regulates its trafficking, membrane expression, and downstream signaling. Several mechanisms for functional regulation of the NR2B-containing NMDA receptor, which have been linked to cognitive dysfunction in schizophrenia, are well known. To analyze whether early events in NR2B processing are affected in schizophrenia, we have isolated a subcellular endoplasmic reticulum (ER)-enriched fraction from postmortem brain and analyzed expression of the NR1 and NR2B NMDA receptor subunits as well as PSD-95 in two areas of prefrontal cortex. We found significantly decreased ER expression of NR2B and PSD-95 in dorsolateral prefrontal cortex in schizophrenia. Analysis in total-cell homogenates from the same subjects of NR2B and PSD-95 expression, as well as of the CINAP and Tbr-1 transcription regulatory proteins, indicate that changes in NR2B processing in schizophrenia involve increased ER exit of NR2B containing NMDA receptors.

No abstract

BACKGROUND:The declining 5-year overall survival (OS) of patients with laryngeal cancer has been associated with increased nonsurgical management of stage III/IV disease. To further assess this hypothesis, the authors evaluated recent OS trends and patterns of use between larynx-preserving approaches with chemoradiation (CRT) or partial laryngectomy (PL) and total laryngectomy (TL) stratified by tumor and nodal burden. METHODS: The National Cancer Data Base was used to identify 8703 patients with stage III/IV (excluding T1 tumors) laryngeal squamous cell carcinoma treated between 2003 and 2011 with CRT or upfront PL or TL with or without adjuvant therapy. OS was analyzed using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Among patients with non-T4, low nodal burden (T2N1 or T3N0-N1) disease, no survival differences were observed between CRT, PL, and TL. Patients who had non-T4, high nodal burden (T2-T3N2-N3) disease who underwent TL with or without adjuvant treatment had a higher risk of death compared with those who received CRT (hazard ratio, 1.25; 95% CI, 1.04-1.51; P = .016). For T4N0-N3 tumors, TL compared with CRT was associated with improved OS (hazard ratio, 0.80; 95% CI, 0.62-0.92; P = .002). No statistically significant difference in outcome was noted between CRT and PL for all stage groups. The use of CRT has declined and receipt of TL has increased since 2006 for T4 disease, whereas PL rates have remained stably low. CONCLUSIONS: No survival differences were noted between surgical and nonsurgical approaches for patients with non-T4, low nodal burden laryngeal cancer. Patients with non-T4, high nodal burden disease may benefit from definitive CRT. Total laryngectomy remains advantageous in patients with T4 disease. Cancer 2019;125:3367-3377.

No abstract

No abstract

No abstract