The control and mechanisms of airway smooth muscle cell (SMC) contraction were investigated with a sequential series of lung slices from different generations of the same airway from the cardiac lobe of the mouse lung. Airway contraction was measured by monitoring the changes in airway lumen area with phase-contrast microscopy. Changes in intracellular calcium concentration of the SMCs were studied with a custom-built confocal or two-photon microscope. The distribution of the airway SMCs and the muscarinic Excessive contraction of airway smooth muscle cells (SMCs) is a major cause of airway narrowing in asthma. This change in the contractile function of SMCs frequently occurs secondarily to airway inflammation, which itself can contribute to increased resistance to airflow by thickening of the airway wall or mucus hypersecretion (1). Although inflammatory responses occur throughout the bronchial tree (2-4), the increased responsiveness and resistance due to airway narrowing appears to be more prevalent in the peripheral airways (1, 5-7). Therefore, to understand this localized reaction, it is important to determine if the contractile responses of SMCs vary in different sections of the respiratory tract and if this predisposes the peripheral airways to disease.Because of their small size and inaccessible location, the physiology of intact intrapulmonary airways has been difficult to study. As a result, comparative reports of the contractile responses in proximal and distal airways of different species are CLINICAL RELEVANCEThis study implies that the heterogeneity of airway contraction must be considered when the impact of the hyperreactivity of a diseased airway is evaluated. inconsistent (8-13). In general, the distal airways appeared more contractile than proximal airways and this difference may result from variations in the structure of the airway wall or the heterogeneity in the SMCs (13). However, a fundamental question is whether the contractility of individual SMC varies in different zones of the intrapulmonary airways. It has been shown that the magnitude of airway SMC contraction relates to the frequency of agonist-induced Ca 2ϩ oscillations within the SMCs (14, 15). Consequently, differences in the Ca 2ϩ signaling mechanism of SMC (e.g., agonist receptor distribution or type) could be responsible for the variation in contraction at different airway locations.The aim of this study was to compare the contractile responses of a range of sizes of intrapulmonary airways and correlate these responses with the intracellular Ca 2ϩ signaling of the SMCs. The observations of SMC contraction and Ca 2ϩ signaling in different airway locations have been made possible by the development of techniques to cut thin serial lung slices that can be observed with microscopy. With this approach, we found that methacholine (MCh) induced a concentration-dependent contraction of SMCs in each generation along the length of an airway through the cardiac lobe of a mouse lung. The greatest contractile response occurred in the mids...

Radiotherapy plays a crucial role in the curative management of localized esophageal cancer, both as definitive and preoperative therapy. For definitive therapy, the standard radiation dose is 50.4 Gy in 28 fractions and should be delivered with concurrent chemotherapy. Chemoradiotherapy also has a wellestablished benefit in the preoperative setting, as established in the CROSS randomized trial. Radiation fields are typically generous, to account for subclinical extension of disease along the esophagus and to regional nodes. Three-dimensional conformal radiation is the current standard technique for esophageal cancer, though intensity-modulated radiation therapy is increasingly utilized and may improve the outcomes of esophageal radiotherapy by reducing radiation dose to critical normal tissues.