Browsing by Author "Phillips, Carrie"

Now showing 1 - 4 of 4
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    Circulating Uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel
    (American Association for the Advancement of Science, 2019-10) LaFavers, Kaice A.; Macedo, Etienne; Garimella, Pranav S.; Lima, Camila; Khan, Shehnaz; Myslinski, Jered; McClintick, Jeanette; Witzmann, Frank A.; Winfree, Seth; Phillips, Carrie; Hato, Takashi; Dagher, Pierre; Wu, Xue-Ru; El-Achkar, Tarek M.; Micanovic, Radmila; Medicine, School of Medicine
    High serum concentrations of kidney-derived protein uromodulin (Tamm-Horsfall protein or THP) have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage. THP in the serum dropped after AKI, and was associated with an increase in systemic ROS. The increase in oxidant injury correlated with post-surgical mortality and need for dialysis. Mechanistically, THP inhibited the activation of the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) channel. Furthermore, inhibition of TRPM2 in vivo in a mouse model, mitigated the systemic increase in ROS during AKI and THP deficiency. Our results suggest that THP is a key regulator of systemic oxidative stress by suppressing TRPM2 activity and our findings might help to explain how circulating THP deficiency is linked with poor outcomes and increased mortality.
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    Deep Tissue Fluorescent Imaging in Scattering Specimens Using Confocal Microscopy
    (Cambridge University Press, 2011-08) Clendenon, Sherry G.; Young, Pamela A.; Ferkowicz, Michael; Phillips, Carrie; Dunn, Kenneth W.; Department of Pediatrics, IU School of Medicine
    In scattering specimens, multiphoton excitation and nondescanned detection improve imaging depth by a factor of 2 or more over confocal microscopy; however, imaging depth is still limited by scattering. We applied the concept of clearing to deep tissue imaging of highly scattering specimens. Clearing is a remarkably effective approach to improving image quality at depth using either confocal or multiphoton microscopy. Tissue clearing appears to eliminate the need for multiphoton excitation for deep tissue imaging.
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    Early Enterococcus-associated acute postinfectious glomerulonephritis after kidney transplant.
    (Oxford University Press, 2014-08) Tandon, Teena; Mujtaba, M.; Mishler, Dennis; Phillips, Carrie; Sharfuddin, Asif; Department of Medicine, IU School of Medicine
    Postinfection as an etiology for glomerulonephritis (GN) is rarely described in post-transplant recipients and may be due to impaired immune response. It is also possible that such cases are not biopsied or not reported. There are rare case reports in the literature. We report here a rare first case of Enterococcus-related postinfectious GN in a transplant recipient seen in our center.
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    Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms
    (Elsevier, 2016-11) Bonsib, Stephen M.; Boils, Christie; Gokden, Neriman; Grignon, David; Gu, Xin; Higgins, John P. T.; Leroy, Xavier; McKenney, Jesse K.; Nasr, Samih H.; Phillips, Carrie; Sangoi, Ankur R.; Wilson, Jon; Zhang, Ping L.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Tuberous sclerosis complex (TSC) results from mutation of TSC1 or TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.