Nitric oxide is a ubiquitous-messenger molecule that can exert proinflammatory, bacteriocidal, and anti-viral actions. Difficulty was found in identifying inducible-nitric oxide synthase (iNS) in humans, but we identified in iNOS in human urinary leukocytes during urinary tract infection, kidney transplant rejection, and bladder cancer. With interstitial cystititis, iNOS activity was decreased compared to iNOS activity from health controls.
The specific aim of this research is to clarify the activators of nitri oxide synthase and the effect that nitric oxide synthase has on leukocytes during disease processes. The mechanism of cellular recruitment into urine with increased and/or decreased NOS activity remains to be investigated. By enzyme activity measurements, by RNA and cDNA evaluation, b immunohistochemistry, and by western blot, NOS and its effectors will be evaluated over time. Also, the interplay between NO and cellular growth and death, interleukins, L-arginine, NADPH-diaphorase, and endothelial-1 will be identified. Assessing NOS during urinary tract infection, urinary tumors, renal transplantation, and interstitial cystitis will aid in understanding No's role in cellular defense and in developing diagnosis and treatment protocols concerning urinary tract disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002499-04
Application #
6176061
Study Section
Special Emphasis Panel (SRC)
Program Officer
Bishop, Terry Rogers
Project Start
1997-07-07
Project End
2001-03-31
Budget Start
2000-05-01
Budget End
2001-03-31
Support Year
4
Fiscal Year
2000
Total Cost
$99,226
Indirect Cost
Name
Yale University
Department
Surgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Swana, H S; Smith, S D; Perrotta, P L et al. (1999) Inducible nitric oxide synthase with transitional cell carcinoma of the bladder. J Urol 161:630-4
Smith, S D; Wheeler, M A; Weiss, R M (1998) Detection of urinary tract infections by reduction of nitroblue tetrazolium. Kidney Int 54:1331-6