Development of glandular models from human nasal progenitor cells.

Hyperplasia/hypertrophy of submucosal glands contributes to mucus overproduction in chronic diseases of the upper and lower respiratory tracts, especially in adult and pediatric chronic rhinosinusitis. Mechanisms that lead to glandular hyperplasia/hypertrophy are markedly understudied, reflecting a lack of in vitro model systems wherein airway epithelial progenitor cells differentiate into glandular cells. In this study, we developed and compared several in vitro three-dimensional systems using human nasal epithelial basal cells (HNEBCs) cultured by different methods on two types of extracellular matrices. We demonstrate that HNEBCs cultured on Matrigel (Corning, Tewksbury, MA) form glandular acini-like structures, whereas HNEBCs embedded in a collagen type I matrix form a network of tubules. Fibroblast-conditioned medium increases tubule formation in collagen type I. In contrast, HNEBCs cocultured with fibroblasts self-aggregate into organotypic structures with tubules and acini. These observations provide morphological evidence that HNEBCs are pluripotent and retain the capacity to differentiate into structures resembling specific structural components of submucosal glands depending on the extracellular matrices and culture conditions. The resultant models should prove useful in targeting cross-talk between epithelial cells and fibroblasts to decipher molecular mechanisms and specific signals responsible for the development of glandular hyperplasia/hypertrophy, which in turn may lead to new therapeutic strategies for chronic rhinosinusitis and other inflammatory respiratory diseases characterized by glandular hyperplasia/hypertrophy.

Visual responsiveness in sensorimotor cortex is increased following amputation and reduced after mirror therapy.

Phantom limb pain (PLP) following amputation, which is experienced by the vast majority of amputees, has been reported to be relieved with daily sessions of mirror therapy. During each session, a mirror is used to view the reflected image of the intact limb moving, providing visual feedback consistent with the movement of the missing/phantom limb. To investigate potential neural correlates of the treatment effect, we measured brain responses in volunteers with unilateral leg amputation using functional magnetic resonance imaging (fMRI) during a four-week course of mirror therapy. Mirror therapy commenced immediately following baseline scans, which were repeated after approximately two and four week intervals. We focused on responses in the region of sensorimotor cortex corresponding to primary somatosensory and motor representations of the missing leg. At baseline, prior to starting therapy, we found a strong and unexpected response in sensorimotor cortex of amputees to visually presented images of limbs. This response was stronger for images of feet compared to hands and there was no such response in matched controls. Further, this response to visually presented limbs was no longer present at the end of the four week mirror therapy treatment, when perceived phantom limb pain was also reduced. A similar pattern of results was also observed in extrastriate and parietal regions typically responsive to viewing hand actions, but not in regions corresponding to secondary somatosensory cortex. Finally, there was a significant correlation between initial visual responsiveness in sensorimotor cortex and reduction in PLP suggesting a potential marker for predicting efficacy of mirror therapy. Thus, enhanced visual responsiveness in sensorimotor cortex is associated with PLP and modulated over the course of mirror therapy.

Extramedullary haematopoiesis presenting with cardiac tamponade in a patient with polycythaemia vera.

A 71-year-old man with a history of polycythaemia vera, diagnosed 4 years ago, presented to the emergency room with shortness of breath. A bedside echocardiogram revealed a large pericardial effusion with features concerning for pericardial tamponade. A left anterior thoracotomy and a pericardial window were emergently performed in the operating room and relieved the patient's symptoms. Histology evaluation of the pericardial fragments and pericardial fluid revealed the presence of trilineage haematopoietic elements without any increase in the blasts. A bone marrow core biopsy revealed an increase in reticulin fibre and increase in the number of blasts of 5%-10%, whereas peripheral blood testing was positive for JAK2 V617F mutation. This case report reviews the literature for cases of extramedullary haematopoiesis associated with myeloproliferative neoplasms.