A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation

The outcome of T cell activation is determined by mechanisms that balance Ca2+ influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn -/-), an immunoglobulin superfamily protein, display elevated cytosolic Ca2+ and impaired post-stimulation Ca2+ clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca2+ ATPases (PMCAs) as the main interaction partners of Neuroplastin. PMCA levels were reduced by over 70% in Nptn -/- T cells, suggesting an explanation for altered Ca2+ handling. Supporting this, Ca2+ extrusion was impaired while Ca2+ levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype of Nptn -/- T cells. Consistent with sustained Ca2+ levels, differentiation of Nptn -/- T helper cells was biased towards the Th1 versus Th2 subset. Our study thus establishes Neuroplastin-PMCA modules as important regulators of T cell activation

Surgery in benign oesophageal disease

Modern approach to benign oesophageal disease comprises endoscopic, laparoscopic and open surgical procedures. The indication for a surgical procedure is in some patients obvious, but in some patients less clear. It is important for patients and for healthcare professionals to have equal goals and expectations of a surgical procedure. The aim of this chapter is to convey to the reader a surgeon’s view on the limitations of surgery for benign oesophageal disease without technical discussions of less interest to non-surgical professionals. Incidence, pathogenesis, imaging, diagnosis, differential diagnoses, treatment, side effects and complications are discussed for most of the common benign disorders such as gastro-oesophageal reflux disease, hernias, strictures, achalasia, eosinophilic oesophagitis, diverticula, haemorrhage, foreign bodies and perforations. Symptoms, and objective findings of failed open or minimally invasive surgical procedures, commonly known by operating surgeons only, are briefly discussed and related to normal postoperative expectations and findings