Absence of Nkx2-3 homeodomain transcription factor reprograms the endothelial addressin preference for lymphocyte homing in Peyer's patches.

Although the homing of lymphocytes to GALT has been extensively studied, little is known about how high endothelial venules (HEVs) within Peyer's patches (PPs) are patterned to display dominantly mucosal addressin cell adhesion molecule 1 (MAdCAM-1). In this study, we report that Nkx2-3-deficient mice show gradual loss of MAdCAM-1 in PPs postnatally and increased levels of mRNA for peripheral lymph node addressin (PNAd) backbone proteins as well as enhanced expression of MECA79 sulfated glycoepitope at the luminal aspect of HEVs, thus replacing MAdCAM-1 with PNAd. Induction of PNAd in mutant PPs requires lymphotoxin ß receptor activity, and its upregulation needs the presence of mature T and B cells. Furthermore, treatment with MECA-79 anti-PNAd mAb in vivo effectively blocks lymphocyte homing to mutant PPs. Despite the replacement of MAdCAM-1 by PNAd in HEV endothelia, lymphocytes could efficiently home to PPs in mutant mice. We conclude that although Nkx2-3 activity controls the addressin balance of HEVs in GALT, the general HEV functionality is preserved independently from Nkx2-3, indicating a substantial plasticity in the specification of GALT HEV endothelium.

Harvey Cushing's experience with cranial deformity.

Surgery for cranial deformity was associated with significant surgical morbidity during the early part of the 20th century. For this reason, Harvey Cushing was initially not in favor of surgical treatment of craniosynostosis. Later in his career, Cushing began to operate on these children, although it never became a major focus of his practice. Several examples of his patients with cranial deformity are presented, and his limited role in the development of this field is discussed.

Emergency suboccipital decompression for respiratory arrest during supratentorial surgery: the untold story of a surgeon's courage in times of despair.

The odyssey leading to the discovery of herniation syndromes was prolonged due to a lack of early understanding of the underlying pathophysiology. In 1896, Leonard Hill documented transtentorial pressure gradients as the intervening phenomenon involved in uncal herniation. In 1904, James Collier became the first to describe cerebellar tonsillar herniation as a "false localizing sign" often associated with intracranial tumors. During the infancy of neurological surgery, management of increased intracranial pressure and an improved understanding of brain herniation syndromes were of the utmost importance in achieving a safe technique. Harvey Cushing provided seminal contributions in understanding the pathophysiology of increased intracranial pressure and resulting cardiopulmonary effects. Cushing believed that tonsillar herniation was a cause of acute cardiorespiratory compromise in patients with intracranial tumors. In this vignette, we describe the untold story of Cushing's heroic attempt to treat respiratory arrest operatively during supratentorial tumor surgery with an emergency suboccipital craniectomy to relieve the medullary dysfunction that he believed was caused by compression from tonsillar herniation. This case illustrates a surgeon's determination and courage in fighting for his patient's life in the most desperate of times.