Constitutively active ezrin increases membrane tension, slows migration, and impedes endothelial transmigration of lymphocytes in vivo in mice.

ERM (ezrin, radixin moesin) proteins in lymphocytes link cortical actin to plasma membrane, which is regulated in part by ERM protein phosphorylation. To assess whether phosphorylation of ERM proteins regulates lymphocyte migration and membrane tension, we generated transgenic mice whose T-lymphocytes express low levels of ezrin phosphomimetic protein (T567E). In these mice, T-cell number in lymph nodes was reduced by 27%. Lymphocyte migration rate in vitro and in vivo in lymph nodes decreased by 18% to 47%. Lymphocyte membrane tension increased by 71%. Investigations of other possible underlying mechanisms revealed impaired chemokine-induced shape change/lamellipod extension and increased integrin-mediated adhesion. Notably, lymphocyte homing to lymph nodes was decreased by 30%. Unlike most described homing defects, there was not impaired rolling or sticking to lymph node vascular endothelium but rather decreased migration across that endothelium. Moreover, decreased numbers of transgenic T cells in efferent lymph suggested defective egress. These studies confirm the critical role of ERM dephosphorylation in regulating lymphocyte migration and transmigration. Of particular note, they identify phospho-ERM as the first described regulator of lymphocyte membrane tension, whose increase probably contributes to the multiple defects observed in the ezrin T567E transgenic mice.

Surgical training and practice.

Surgery has had a long history and rich heritage in its practice and training. From a craft based vocation some 500 years ago, it has evolved into a noble profession based on science. The remarkable scientific and technological advances during the last century have made surgery safer and the quality of life better for the patient. However, the cost and quality of health care delivery and public expectation are major issues to deal with. The changing face of surgery needs a more structured training program and major commitment of trainees and surgeons. The challenge for the future surgeon and trainee is to constantly learn new skills and competencies including new professionalism to deliver high-quality care.

Surgery in Singapore.

Since Singapore became an independent nation about 50 years ago, remarkable progress has been made in the development and organization of the health care system, specialty services, graduate training, and medical research. The primitive health care service under the British colonial service before the Second World War which was further ravaged in the 1940s by the Japanese occupation has been radically transformed in a short period. Singapore has a modern health care service, excellent hospital facilities, an affordable health financing system, adequate medical manpower including specialists, and a postgraduate organization for the training of medical specialists. The advancement in surgical services has reached a high level where all forms of modern surgery, including laparoscopic and endoscopic operations, are routine and major bone and joint replacements, heart and liver transplantations, and complex neurosurgical and craniofacial operations are frequently carried out.

Surgical training - the challenge of change.

The healthcare environment is continuing to change and so too is education and training of surgeons. We now live in an age of increased specialisation, of technology, of accountability, of greater patient education and expectation and mass media attention. The traditional apprentice method and emphasis too much on examinations will have to be changed to a more structured system of training with training standards, regular assessment and feed back. There are new skills to be learnt for future surgical practice and new ways to learn them to become competent. We need to make changes in the institutions and departments to create a learning environment and an organisational system to implement the training programme. The current shortage of surgical work force in the institutions and lack of sufficient teachers committed to teaching and training are major issues that need to be addressed.