Browsing by Author "Corcoran, David L."

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    Metabolic Changes with Base-Loading in CKD
    (American Society of Nephrology, 2018-08-07) Scialla, Julia J.; Brown, Landon; Gurley, Susan; Corcoran, David L.; Bain, James R.; Muehlbauer, Michael J.; O’Neal, Sara K.; M. O’Connell, Thomas; Wolf, Myles; Melamed, Michal L.; Hostetter, Thomas H.; Abramowitz, Matthew K.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    In small, randomized studies, treatment with sodium bicarbonate slowed kidney function decline in patients with CKD, possibly by lowering urine ammonium or inhibiting the renin-angiotensin-aldosterone or endothelin-1 pathways (1). Understanding the metabolic effects of alkali supplementation may reveal new candidate mechanisms. With this goal in mind, we profiled changes in systemic metabolites after treatment with sodium bicarbonate within a previously performed crossover trial of oral sodium bicarbonate (2).
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    Pax3 expression enhances PDGF-B-induced brainstem gliomagenesis and characterizes a subset of brainstem glioma
    (BioMed Central, 2014-10-21) Misuraca, Katherine L.; Barton, Kelly L.; Chung, Alexander; Diaz, Alexander K.; Conway, Simon J.; Corcoran, David L.; Baker, Suzanne J.; Becher, Oren J.; Department of Pediatrics, School of Medicine
    High-grade Brainstem Glioma (BSG), also known as Diffuse Intrinsic Pontine Glioma (DIPG), is an incurable pediatric brain cancer. Increasing evidence supports the existence of regional differences in gliomagenesis such that BSG is considered a distinct disease from glioma of the cerebral cortex (CG). In an effort to elucidate unique characteristics of BSG, we conducted expression analysis of mouse PDGF-B-driven BSG and CG initiated in Nestin progenitor cells and identified a short list of expression changes specific to the brainstem gliomagenesis process, including abnormal upregulation of paired box 3 (Pax3). In the neonatal mouse brain, Pax3 expression marks a subset of brainstem progenitor cells, while it is absent from the cerebral cortex, mirroring its regional expression in glioma. Ectopic expression of Pax3 in normal brainstem progenitors in vitro shows that Pax3 inhibits apoptosis. Pax3-induced inhibition of apoptosis is p53-dependent, however, and in the absence of p53, Pax3 promotes proliferation of brainstem progenitors. In vivo, Pax3 enhances PDGF-B-driven gliomagenesis by shortening tumor latency and increasing tumor penetrance and grade, in a region-specific manner, while loss of Pax3 function extends survival of PDGF-B-driven;p53-deficient BSG-bearing mice by 33%. Importantly, Pax3 is regionally expressed in human glioma as well, with high PAX3 mRNA characterizing 40% of human BSG, revealing a subset of tumors that significantly associates with PDGFRA alterations, amplifications of cell cycle regulatory genes, and is exclusive of ACVR1 mutations. Collectively, these data suggest that regional Pax3 expression not only marks a novel subset of BSG but also contributes to PDGF-B-induced brainstem gliomagenesis.
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    Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study
    (MDPI, 2021-05-22) Pourafshar, Shirin; Nicchitta, Mira; Tyson, Crystal C.; Svetkey, Laura P.; Corcoran, David L.; Bain, James R.; Muehlbauer, Michael J.; Ilkayeva, Olga; O’Connell, Thomas M; Lin, Pao-Hwa; Scialla, Julia J.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry. Linear models were used to compare metabolite levels between the groups. In urine, 19 identifiable untargeted metabolites differed between groups at p < 0.05. These included a variety of phenolic acids and their microbial metabolites that were higher during the DASH diet, with many at false discovery rate (FDR) adjusted p < 0.2. In plasma, eight identifiable untargeted metabolites were different at p < 0.05, but only gamma-tocopherol was significantly lower on DASH at FDR adjusted p < 0.2. The results provide insights into the mechanisms of benefit of the DASH diet.