The Pathology Core has been highly successful in the identification of tissue changes and characterizing sites of mineral deposition as well as crystal type in three different type of human stone patients (common CaOx, intestinal bypass patients for obesity with renal stones and brushite) and the GHS rats. In the renewal, this core will oversee and conduct all morphological analyses for Projects by Lingeman and Evans using 1) light micrscopy with special stains to characterize the histopathological patterns and mineral composition of crystal deposition in our new groups of human stone formers (apatite including RTAs, primary hyperparathyroidism, ileostomy, cystinuria, uric acid stones, bariatric and CaOx with high urine pH (> pH 6.3), 2) light and transmission electron microscopic immunohistochemistry to detect the presence of a select group of known inhibitor proteins of crystal formation (osteopontin, prothombin fragment 1, fetuin-A and bikunin) in the interstitium and at the stone-plaque interface, 3) mu CT imaging to quantitate, localize and characterize mineral type of new sites of crystal deposition in whole kidneys or biopsies samples. 4) mu FTIR and electron diffraction detection techniques to identify specific sites of crystal deposition in human biopsy samples and GHS rat kidneys, 5) RT-PCR techniques to determine the presence of osteoblast-like transcripts in the interstitium of the common CaOx stone formers vs intestinal bypass or bariatric stone formers, 6) determine the mechanisms of crystal particle formation and coalescence in CaOx stone formers by quantitating particle growth/coalescence and performing double labeling, tetracyline studies to determine the rate of crystal formation, 7) provide cortical biopsy samples to Project by Coe for VDR analysis and verification of biopsy location, and 8) to assess the GHS rat for plaque formation. Project by Lingeman will supply biopsy samples from the kidney (cortex to papilla) of predetermined groups of human stone formers. Dr. Willis will perform serum and urinary lithium analyses for Project by Coe.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK056788-08
Application #
7490032
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2007-09-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
8
Fiscal Year
2007
Total Cost
$129,243
Indirect Cost
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Williams Jr, James C; Borofsky, Michael S; Bledsoe, Sharon B et al. (2018) Papillary Ductal Plugging is a Mechanism for Early Stone Retention in Brushite Stone Disease. J Urol 199:186-192
Worcester, Elaine M; Bergsland, Kristin J; Gillen, Daniel L et al. (2018) Mechanism for higher urine pH in normal women compared with men. Am J Physiol Renal Physiol 314:F623-F629
Bergsland, Kristin J; Coe, Fredric L; Parks, Joan H et al. (2018) Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers. Nephrol Dial Transplant 33:759-770
Kleinguetl, Colin; Williams Jr, James C; Ibrahim, Samar A et al. (2017) Calcium Tartrate Tetrahydrate, Case Report of a Novel Human Kidney Stone. J Endourol Case Rep 3:192-195
Mulay, Shrikant R; Eberhard, Jonathan N; Desai, Jyaysi et al. (2017) Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease. J Am Soc Nephrol 28:761-768
Winfree, Seth; Khan, Shehnaz; Micanovic, Radmila et al. (2017) Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune Cells. J Am Soc Nephrol 28:2108-2118
Borofsky, Michael S; Dauw, Casey A; York, Nadya et al. (2017) Accuracy of daily fluid intake measurements using a ""smart"" water bottle. Urolithiasis :
Winfree, Seth; Ferkowicz, Michael J; Dagher, Pierre C et al. (2017) Large-scale 3-dimensional quantitative imaging of tissues: state-of-the-art and translational implications. Transl Res 189:1-12
Cohen, Andrew J; Borofsky, Michael S; Anderson, Blake B et al. (2017) Endoscopic Evidence That Randall's Plaque is Associated with Surface Erosion of the Renal Papilla. J Endourol 31:85-90
Gilad, Ron; Williams Jr, James C; Usman, Kalba D et al. (2017) Interpreting the results of chemical stone analysis in the era of modern stone analysis techniques. J Nephrol 30:135-140

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