Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.

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305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.

Background: To examine the association of preoperative Mayo Adhesive Probability (MAP) scores in the donor (MAP d) and non-donor kidneys (MAP nd) with post-donation renal function. Methods: Three hundred thirty-one patients undergoing hand assisted laparoscopic donor nephrectomy (HALDN) were reviewed. MAP d and MAP nd were obtained. Estimated glomerular filtration rate (eGFR) was recorded preoperatively and at 1 day, 1 month, and 6 months postoperatively. Results: Two hundred females and 131 males were evaluated with median BMI 26.4 kg/m 2 (range 17.1-39.6) and median age 45 years (range 19-78). MAP d score was 0 for 231 patients (69.8%) and > 0 for 100 patients (30.2%). MAP nd score was 0 for 234 patients (70.7%) and > 0 for 97 patients (29.3%). The median preoperative eGFR was 86.6 ml/min/ 1.73m 2 (range 48.8-138.4). After adjusting for preoperative eGFR, BMI, ASA score, and kidney sidedness, postoperative eGFR was associated with MAP score in the non-donated kidney (p = 0.014) but not in the donated kidney (p = 0.24). Compared to donors with MAP nd = 0, donors with a MAP nd > 0, mean eGFR was − 2.33 ml/min/1.73m 2 lower at postoperative day 1 (95% CI − 4.24 to − 0.41, p = 0.018), − 3.02 ml/min/1.73m 2 lower at 1 month (95% CI − 5.11 to − 0.93, p = 0.005), and − 2.63 ml/min/1.73m 2 lower at 6 months postoperatively (95% CI − 5.01 to − 0.26, p = 0.030). Conclusions: MAP score > 0 in the non-donated kidney is associated with worse renal function in the 6 months following HALDN.