The American journal of the medical sciences
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Time-dependent PPARγ Modulation of HIF-1α Signaling in Hypoxic Pulmonary Artery Smooth Muscle Cells.
Pathogenesis of pulmonary hypertension is complex and involves activation of the transcription factor, hypoxia-inducible factor-1 (HIF-1) that shifts cellular metabolism from aerobic respiration to glycolysis, in part, by increasing the expression of its downstream target pyruvate dehydrogenase kinase-1 (PDK-1), thereby promoting a proliferative, apoptosis-resistant phenotype in pulmonary vascular cells. Activation of the nuclear hormone transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), attenuates pulmonary hypertension and pulmonary artery smooth muscle cell (PASMC) proliferation. In the current study, we determined whether PPARγ inhibits HIF-1α and PDK-1 expression in human PASMCs. ⋯ Hypoxia causes transient activation of HPASMC HIF-1α that is attenuated by RSG treatment initiated at hypoxia onset. These findings provide novel evidence that PPARγ modulates fundamental and acute cellular responses to hypoxia through both HIF-1-dependent and HIF-1-independent mechanisms.
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Letter Case Reports
An Incidental Finding of Bilateral Adrenal Lymphoma.
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The relationship between the seniority of emergency physicians (EPs) and disposition decision-making is not well defined. As most responsibility by EPs involves developing an appropriate disposition plan, this study aimed to examine the influence of EP seniority on decisions regarding patient dispositions in the emergency department (ED). ⋯ Senior EPs had the best quality of care (lowest mortality, fewest 72-hour returns). This best quality of care is accompanied with a slightly longer length of stay.