42 research outputs found

    Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model

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    <p>Abstract</p> <p>Objective</p> <p>The phenomena manifested during inflammation require interplay between circulating effector cells, local resident cells, soluble mediators and genetic host factors to establish, develop and maintain itself. Of the molecues involed in the initiation and perpetuation of acute allergic inflammation in asthma, the involvement of effector cells in redox reactions for producing O<sub>2</sub><sup>- </sup>(superoxide anion) through the mediation of NADPH oxidase is a critical step. Prior data suggest that reactive oxygen species (ROS) produced by NADPH oxidase homologues in non-phagocytic cells play an important role in the regulation of signal transduction, while macrophages use a membrane-associated NADPH oxidase to generate an array of oxidizing intermediates which inactivate MMPs on or near them.</p> <p>Materials and Methods and Treatment</p> <p>To clarify the role of gp91phox subunit of NADPH oxidase in the development and progression of an acute allergic asthma phenotype, we induced allergen dependent inflammation in a gp91<it><sup>phox</sup></it>-/- single knockout and a gp91phox-/-MMP-12-/- double knockout mouse models.</p> <p>Results</p> <p>In the knockout mice, both inflammation and airway hyperreactivity were more extensive than in wildtype mice post-OVA. Although OVA-specific IgE in plasma were comparable in wildtype and knockout mice, enhanced inflammatory cell recruitment from circulation and cytokine release in lung and BALf, accompanied by higher airway resistance as well as Penh in response to methacholine, indicate a regulatory role for NADPH oxidase in development of allergic asthma. While T cell mediated functions like Th2 cytokine secretion, and proliferation to OVA were upregulated synchronous with the overall robustness of the asthma phenotype, macrophage upregulation in functions such as proliferation, and mixed lymphocyte reaction indicate a regulatory role for gp91phox and an overall non-involvement or synergistic involvement of MMP12 in the response pathway (comparing data from gp91phox-/- and gp91phox-/-MMP-12-/- mice).</p

    What a medical school chair wants from the dean

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    Robert Hromas,1 Robert Leverence,1 Lazarus K Mramba,2 J Larry Jameson,3 Caryn Lerman,3 Thomas L Schwenk,4 Ellen M Zimmermann,2 Michael L Good51The Office of the Dean, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA; 2Department of Medicine, College of Medicine, University of Florida Health, Gainesville, FL, USA; 3Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 4Department of Family Medicine, School of Medicine, University of Nevada Reno, Reno, NV, USA; 5Department of Anesthesiology, College of Medicine, University of Florida Health, Gainesville, FL, USAAbstract: Economic pressure has led the evolution of the role of the medical school dean from a clinician educator to a health care system executive. In addition, other dynamic requirements also have likely led to changes in their leadership characteristics. The most important relationship a dean has is with the chairs, yet in the context of the dean&rsquo;s changing role, little attention has been paid to this relationship. To frame this discussion, we asked medical school chairs what characteristics of a dean&rsquo;s leadership were most beneficial. We distributed a 26-question survey to 885 clinical and basic science chairs at 41 medical schools. These chairs were confidentially surveyed on their views of six leadership areas: evaluation, barriers to productivity, communication, accountability, crisis management, and organizational values. Of the 491 chairs who responded (response rate =55%), 88% thought that their dean was effective at leading the organization, and 89% enjoyed working with their dean. Chairs indicated that the most important area of expertise of a dean is to define a strategic vision, and the most important value for a dean is integrity between words and deeds. Explaining the reasons behind decisions, providing good feedback, admitting errors, open discussion of complex or awkward topics, and skill in improving relations with the teaching hospital were judged as desirable attributes of a dean. Interestingly, only 23% of chairs want to be a dean in the future. Financial acumen was the least important skill a chair thought a dean should hold, which is in contrast to the skill set for which many deans are hired and evaluated. After reviewing the literature and analyzing these responses, we assert that medical school chairs want their dean to maintain more traditional leadership than that needed by a health care system executive, such as articulating a vision for the future and keeping their promises. Thus, there appears to be a mismatch between what medical school chairs perceive they need from their dean and how the success of a dean is evaluated. Keywords: academic medicine deans, leadership characteristics, organizational value
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