The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Jahar Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
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acid contact in the rodent Pulmonary Alveolus causes proinflammatory signaling by membrane pore formation
American Journal of Physiology-lung Cellular and Molecular Physiology, 2012Co-Authors: Kristin Westphalen, Eiji Monma, Mohammad N Islam, Jahar BhattacharyaAbstract:Although gastric acid aspiration causes rapid lung inflammation and acute lung injury, the initiating mechanisms are not known. To determine alveolar epithelial responses to acid, we viewed live alveoli of the isolated lung by fluorescence microscopy, then we microinjected the alveoli with HCl at pH of 1.5. The microinjection caused an immediate but transient formation of molecule-scale pores in the apical alveolar membrane, resulting in loss of cytosolic dye. However, the membrane rapidly resealed. There was no cell damage and no further dye loss despite continuous HCl injection. Concomitantly, reactive oxygen species (ROS) increased in the adjacent perialveolar microvascular endothelium in a Ca2+-dependent manner. By contrast, ROS did not increase in wild-type mice in which we gave intra-alveolar injections of polyethylene glycol (PEG)-catalase, in mice overexpressing alveolar catalase, or in mice lacking functional NADPH oxidase (Nox2). Together, our findings indicate the presence of an unusual proinflammatory mechanism in which alveolar contact with acid caused membrane pore formation. The effect, although transient, was nevertheless sufficient to induce Ca2+ entry and Nox2-dependent H2O2 release from the alveolar epithelium. These responses identify alveolar H2O2 release as the signaling mechanism responsible for lung inflammation induced by acid and suggest that intra-alveolar PEG-catalase might be therapeutic in acid-induced lung injury.
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ca2 i oscillations regulate type ii cell exocytosis in the Pulmonary Alveolus
American Journal of Physiology-lung Cellular and Molecular Physiology, 2000Co-Authors: Yugo Ashino, Xiaoyou Ying, Leland G Dobbs, Jahar BhattacharyaAbstract:Pulmonary surfactant, a critical determinant of alveolar stability, is secreted by alveolar type II cells by exocytosis of lamellar bodies (LBs). To determine exocytosis mechanisms in situ, we imag...
Pierre Chambon - One of the best experts on this subject based on the ideXlab platform.
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Retinoic acid receptor-α regulates Pulmonary Alveolus formation in mice after, but not during, perinatal period
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Gloria Decarlo Massaro, Donald Massaro, Pierre ChambonAbstract:The formation of Pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatalday 14. However, alveoli con...
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retinoic acid receptor α regulates Pulmonary Alveolus formation in mice after but not during perinatal period
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Gloria Decarlo Massaro, Donald Massaro, Pierre ChambonAbstract:The formation of Pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatal day 14. However, alveoli continue to form after age 14 days until age approximately 40 days by means other than septation of the saccules present at birth. With the use of morphometric procedures and retinoic acid receptor (RAR)-alpha+/+ and RAR-alpha-/- mice, we now show the volume of individual alveoli (va), the number of alveoli (Na), and alveolar surface area (Sa) are the same in 14-day-old RAR-alpha+/+ and RAR-alpha-/- mice. However, at age 50 days, va is larger, and Na and Sa are smaller, in RAR-alpha-/- than in RAR-alpha+/+ mice, although total lung volume is the same in both groups. These findings, and prior data showing RAR-beta is an endogenous inhibitor of Alveolus formation during, but not after, the perinatal period, indicate there are developmental period-specific regulators of Alveolus formation and that total lung volume and alveolar dimensions may have different regulators.
Gloria Decarlo Massaro - One of the best experts on this subject based on the ideXlab platform.
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Running head: Estrogen, alveolar stability and regeneration Correspondence to:
2013Co-Authors: Lcmp-- R, Gloria Decarlo Massaro, Donald Massaro, Donald Massaro M. DAbstract:Estrogen receptors regulate Pulmonary Alveolus formation and estrogen is required for alveolar architectural stability, and induces alveolar regeneration in mice
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Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment: Novartis Foundation Symposium 234 - Pulmonary Alveolus formation: critical period, retinoid regulation and plasticity.
Novartis Foundation symposium, 2008Co-Authors: Donald Massaro, Gloria Decarlo MassaroAbstract:Pulmonary alveoli, the lung's gas-exchange structures, are formed in part by subdivision (septation) of the saccules that constitute the gas-exchange region of the immature lung. Although little is known about the regulation of septation, relatively recent studies show: (1) all-trans retinoic acid (RA) treatment of newborn rats increases septation and prevents the inhibition of septation produced by treatment of newborn rats with dexamethasone, a glucocorticosteroid hormone; (2) treatment with RA of adult rats that have elastase-induced emphysema increases lung elastic recoil, induces the formation of alveoli, and increases volume-corrected alveolar surface area; and (3) in tight-skin mice, which have a genetic failure of septation, and in rats in which septation had previously been prevented by treatment with dexamethasone, treatment with RA partially rescues the failed septation. These findings raise the possibility that treatment with RA will induce the formation of alveoli in humans with Pulmonary emphysema.
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Retinoic acid receptor-α regulates Pulmonary Alveolus formation in mice after, but not during, perinatal period
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Gloria Decarlo Massaro, Donald Massaro, Pierre ChambonAbstract:The formation of Pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatalday 14. However, alveoli con...
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retinoic acid receptor α regulates Pulmonary Alveolus formation in mice after but not during perinatal period
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Gloria Decarlo Massaro, Donald Massaro, Pierre ChambonAbstract:The formation of Pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatal day 14. However, alveoli continue to form after age 14 days until age approximately 40 days by means other than septation of the saccules present at birth. With the use of morphometric procedures and retinoic acid receptor (RAR)-alpha+/+ and RAR-alpha-/- mice, we now show the volume of individual alveoli (va), the number of alveoli (Na), and alveolar surface area (Sa) are the same in 14-day-old RAR-alpha+/+ and RAR-alpha-/- mice. However, at age 50 days, va is larger, and Na and Sa are smaller, in RAR-alpha-/- than in RAR-alpha+/+ mice, although total lung volume is the same in both groups. These findings, and prior data showing RAR-beta is an endogenous inhibitor of Alveolus formation during, but not after, the perinatal period, indicate there are developmental period-specific regulators of Alveolus formation and that total lung volume and alveolar dimensions may have different regulators.
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Pulmonary Alveolus formation critical period retinoid regulation and plasticity
Novartis Foundation symposium, 2001Co-Authors: Donald Massaro, Gloria Decarlo MassaroAbstract:Pulmonary alveoli, the lung's gas-exchange structures, are formed in part by subdivision (septation) of the saccules that constitute the gas-exchange region of the immature lung. Although little is known about the regulation of septation, relatively recent studies show: (1) all-trans retinoic acid (RA) treatment of newborn rats increases septation and prevents the inhibition of septation produced by treatment of newborn rats with dexamethasone, a glucocorticosteroid hormone; (2) treatment with RA of adult rats that have elastase-induced emphysema increases lung elastic recoil, induces the formation of alveoli, and increases volume-corrected alveolar surface area; and (3) in tight-skin mice, which have a genetic failure of septation, and in rats in which septation had previously been prevented by treatment with dexamethasone, treatment with RA partially rescues the failed septation. These findings raise the possibility that treatment with RA will induce the formation of alveoli in humans with Pulmonary emphysema.
Ajay K. Prasad - One of the best experts on this subject based on the ideXlab platform.
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flow and particle dispersion in a Pulmonary Alveolus part i velocity measurements and convective particle transport
Journal of Biomechanical Engineering-transactions of The Asme, 2010Co-Authors: Sudhaker Chhabra, Ajay K. PrasadAbstract:The alveoli are the smallest units of the lung that participate in gas exchange. Although gas transport is governed primarily by diffusion due to the small length scales associated with the acinar region (~500 μm), the transport and deposition of inhaled aerosol particles are influenced by convective airflow patterns. Therefore, understanding alveolar fluid flow and mixing is a necessary first step toward predicting aerosol transport and deposition in the human acinar region. In this study, flow patterns, and particle transport have been measured using a simplified in-vitro alveolar model consisting of a single Alveolus located on a bronchiole. The model comprises a transparent elastic 5/6 spherical cap (representing the Alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The Alveolus is capable of expanding and contracting in phase with the oscillatory flow through the tube. Realistic breathing conditions were achieved by exercising the model at physiologically relevant Reynolds and Womersley numbers. Particle image velocimetry was used to measure the resulting flow patterns in the Alveolus. Data were acquired for five cases obtained as combinations of the alveolar-wall motion (nondeforming/oscillating) and the bronchiole flow (none/ steady/oscillating). Detailed vector maps at discrete points within a given cycle revealed flow patterns, and transport and mixing of bronchiole fluid into the alveolar cavity. The time-dependent velocity vector fields were integrated over multiple cycles to estimate particle transport into the alveolar cavity and deposition on the alveolar wall. The key outcome of the study is that alveolar-wall motion enhances mixing between the bronchiole and the alveolar fluid. Particle transport and deposition into the alveolar cavity are maximized when the alveolar wall oscillates in tandem with the bronchiole fluid, which is the operating case in the human lung. [DOI: 10.1115/1.4001112].
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Flow and Particle Dispersion in a Pulmonary Alveolus—Part I: Velocity Measurements and Convective Particle Transport
Journal of biomechanical engineering, 2010Co-Authors: Sudhaker Chhabra, Ajay K. PrasadAbstract:The alveoli are the smallest units of the lung that participate in gas exchange. Although gas transport is governed primarily by diffusion due to the small length scales associated with the acinar region (~500 μm), the transport and deposition of inhaled aerosol particles are influenced by convective airflow patterns. Therefore, understanding alveolar fluid flow and mixing is a necessary first step toward predicting aerosol transport and deposition in the human acinar region. In this study, flow patterns, and particle transport have been measured using a simplified in-vitro alveolar model consisting of a single Alveolus located on a bronchiole. The model comprises a transparent elastic 5/6 spherical cap (representing the Alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The Alveolus is capable of expanding and contracting in phase with the oscillatory flow through the tube. Realistic breathing conditions were achieved by exercising the model at physiologically relevant Reynolds and Womersley numbers. Particle image velocimetry was used to measure the resulting flow patterns in the Alveolus. Data were acquired for five cases obtained as combinations of the alveolar-wall motion (nondeforming/oscillating) and the bronchiole flow (none/ steady/oscillating). Detailed vector maps at discrete points within a given cycle revealed flow patterns, and transport and mixing of bronchiole fluid into the alveolar cavity. The time-dependent velocity vector fields were integrated over multiple cycles to estimate particle transport into the alveolar cavity and deposition on the alveolar wall. The key outcome of the study is that alveolar-wall motion enhances mixing between the bronchiole and the alveolar fluid. Particle transport and deposition into the alveolar cavity are maximized when the alveolar wall oscillates in tandem with the bronchiole fluid, which is the operating case in the human lung. [DOI: 10.1115/1.4001112].
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Flow and particle dispersion in a Pulmonary Alveolus--part II: effect of gravity on particle transport.
Journal of biomechanical engineering, 2010Co-Authors: Sudhaker Chhabra, Ajay K. PrasadAbstract:The acinar region of the human lung comprises about 300 X 10 6 alveoli, which are responsible for gas exchange between the lung and the blood. As discussed in Part I (Chhabra and Prasad, "Flow and Particle Dispersion in a Pulmonary Alveolus-Part I: Velocity Measurements and Convective Particle Transport, " ASME J. Biomech. Eng., 132, p. 051009), the deposition of aerosols in the acinar region can either be detrimental to gas exchange (as in the case of harmful particulate matter) or beneficial (as in the case of inhalable pharmaceuticals). We measured the flow field inside an in-vitro model of a single Alveolus mounted on a bronchiole and calculated the transport and deposition of massless particles in Part I. This paper focuses on the transport and deposition of finite-sized particles ranging from 0.25 μm to 4 μm under the combined influence of flow-induced advection (computed from velocity maps obtained by particle image velocimetry) and gravitational settling. Particles were introduced during the first inhalation cycle and their trajectories and deposition statistics were calculated for subsequent cycles for three different particle sizes (0.25 μm, I μm, and 4 μm) and three alveolar orientations. The key outcome of the study is that particles ≤0.25 μm follow the fluid streamlines quite closely, whereas midsize particles (d p =1 μm) deviate to some extent from streamlines and exhibit complex trajectories. The motion of large particles ≥4 μm is dominated by gravitational settling and shows little effect of fluid advection. Additionally, small and midsize particles deposit at about two-thirds height in the Alveolus irrespective of the gravitational orientation whereas the deposition of large particles is governed primarily by the orientation of the gravity vector.
Donald Massaro - One of the best experts on this subject based on the ideXlab platform.
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Running head: Estrogen, alveolar stability and regeneration Correspondence to:
2013Co-Authors: Lcmp-- R, Gloria Decarlo Massaro, Donald Massaro, Donald Massaro M. DAbstract:Estrogen receptors regulate Pulmonary Alveolus formation and estrogen is required for alveolar architectural stability, and induces alveolar regeneration in mice
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Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment: Novartis Foundation Symposium 234 - Pulmonary Alveolus formation: critical period, retinoid regulation and plasticity.
Novartis Foundation symposium, 2008Co-Authors: Donald Massaro, Gloria Decarlo MassaroAbstract:Pulmonary alveoli, the lung's gas-exchange structures, are formed in part by subdivision (septation) of the saccules that constitute the gas-exchange region of the immature lung. Although little is known about the regulation of septation, relatively recent studies show: (1) all-trans retinoic acid (RA) treatment of newborn rats increases septation and prevents the inhibition of septation produced by treatment of newborn rats with dexamethasone, a glucocorticosteroid hormone; (2) treatment with RA of adult rats that have elastase-induced emphysema increases lung elastic recoil, induces the formation of alveoli, and increases volume-corrected alveolar surface area; and (3) in tight-skin mice, which have a genetic failure of septation, and in rats in which septation had previously been prevented by treatment with dexamethasone, treatment with RA partially rescues the failed septation. These findings raise the possibility that treatment with RA will induce the formation of alveoli in humans with Pulmonary emphysema.
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Retinoic acid receptor-α regulates Pulmonary Alveolus formation in mice after, but not during, perinatal period
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Gloria Decarlo Massaro, Donald Massaro, Pierre ChambonAbstract:The formation of Pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatalday 14. However, alveoli con...
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retinoic acid receptor α regulates Pulmonary Alveolus formation in mice after but not during perinatal period
American Journal of Physiology-lung Cellular and Molecular Physiology, 2003Co-Authors: Gloria Decarlo Massaro, Donald Massaro, Pierre ChambonAbstract:The formation of Pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatal day 14. However, alveoli continue to form after age 14 days until age approximately 40 days by means other than septation of the saccules present at birth. With the use of morphometric procedures and retinoic acid receptor (RAR)-alpha+/+ and RAR-alpha-/- mice, we now show the volume of individual alveoli (va), the number of alveoli (Na), and alveolar surface area (Sa) are the same in 14-day-old RAR-alpha+/+ and RAR-alpha-/- mice. However, at age 50 days, va is larger, and Na and Sa are smaller, in RAR-alpha-/- than in RAR-alpha+/+ mice, although total lung volume is the same in both groups. These findings, and prior data showing RAR-beta is an endogenous inhibitor of Alveolus formation during, but not after, the perinatal period, indicate there are developmental period-specific regulators of Alveolus formation and that total lung volume and alveolar dimensions may have different regulators.
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Pulmonary Alveolus formation critical period retinoid regulation and plasticity
Novartis Foundation symposium, 2001Co-Authors: Donald Massaro, Gloria Decarlo MassaroAbstract:Pulmonary alveoli, the lung's gas-exchange structures, are formed in part by subdivision (septation) of the saccules that constitute the gas-exchange region of the immature lung. Although little is known about the regulation of septation, relatively recent studies show: (1) all-trans retinoic acid (RA) treatment of newborn rats increases septation and prevents the inhibition of septation produced by treatment of newborn rats with dexamethasone, a glucocorticosteroid hormone; (2) treatment with RA of adult rats that have elastase-induced emphysema increases lung elastic recoil, induces the formation of alveoli, and increases volume-corrected alveolar surface area; and (3) in tight-skin mice, which have a genetic failure of septation, and in rats in which septation had previously been prevented by treatment with dexamethasone, treatment with RA partially rescues the failed septation. These findings raise the possibility that treatment with RA will induce the formation of alveoli in humans with Pulmonary emphysema.
