A five-fold program has been developed in which the central theme is the enzyme carbonic anhydrase (C.A.), its chemistry, inhibition, and role in certain organ systems, presently unknown. The continuity between biochemical and physiological events is stressed. We plan to study the following: I. The role of carbonic anhydrase in muscle, uterus, ova, and secretion of endolymph. This introduces also fundamental questions about the physiology of these organs. Particularly, in muscle we shall study CO2 output after inhibition of the enzyme; in uterus the implantation evironment; in ova the dispersion of the corona radiata; in endolymph the rate and character of secretion. II. We shall study the role of CO2 in neutral secretions (NaCl) and whether there can be renal H+ output independent of the CO2 system. III. New sulfonamide inhibitors combining lipid and water solubility will be developed. Studies of drug-enzyme kinetics will be pursued, with attention ot """"""""uncompetitive"""""""" inhibition, and differences between the three C.A. isozymes. IV. We wish to characterize mitochondrial C.A., and also the enzyme in brain myelin, with respect to Kcat, Km, and susceptibility to inhibition by the sulfonamides. V. We plan to study gas exchange and acid-base balance in sub-order of Amphibia, the plethodonts, which lack both lungs and gills, and respire entirely through the skin. They are also the only adult vertebrates that lack red cell C.A.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL022258-08
Application #
3336805
Study Section
(SSS)
Project Start
1978-04-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Steidle-Kloc, Eva; Culvenor, Adam G; Dörrenberg, Jan et al. (2018) Relationship Between Knee Pain and Infrapatellar Fat Pad Morphology: A Within- and Between-Person Analysis From the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 70:550-557
Kashyap, Satyananda; Zhang, Honghai; Rao, Karan et al. (2018) Learning-Based Cost Functions for 3-D and 4-D Multi-Surface Multi-Object Segmentation of Knee MRI: Data From the Osteoarthritis Initiative. IEEE Trans Med Imaging 37:1103-1113
Fernandes, G S; Bhattacharya, A; McWilliams, D F et al. (2017) Risk prediction model for knee pain in the Nottingham community: a Bayesian modelling approach. Arthritis Res Ther 19:59
Dunlop, Dorothy D; Song, Jing; Lee, Jungwha et al. (2017) Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower-Extremity Symptoms. Arthritis Care Res (Hoboken) 69:475-483
LaValley, Michael P; Lo, Grace H; Price, Lori Lyn et al. (2017) Development of a clinical prediction algorithm for knee osteoarthritis structural progression in a cohort study: value of adding measurement of subchondral bone density. Arthritis Res Ther 19:95
Sharma, Leena; Chang, Alison H; Jackson, Rebecca D et al. (2017) Varus Thrust and Incident and Progressive Knee Osteoarthritis. Arthritis Rheumatol 69:2136-2143
Dai, Zhaoli; Lu, Na; Niu, Jingbo et al. (2017) Dietary Fiber Intake in Relation to Knee Pain Trajectory. Arthritis Care Res (Hoboken) 69:1331-1339
Han, Bobby Kwanghoon; Kim, Woojin; Niu, Jingbo et al. (2017) Association of Chondrocalcinosis in Knee Joints With Pain and Synovitis: Data From the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 69:1651-1658
Culvenor, Adam G; Wirth, Wolfgang; Roth, Melanie et al. (2016) Predictive Capacity of Thigh Muscle Strength in Symptomatic and/or Radiographic Knee Osteoarthritis Progression: Data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium. Am J Phys Med Rehabil 95:931-938
Bowes, Michael A; McLure, Stewart Wd; Wolstenholme, Christopher Bh et al. (2016) Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the Osteoarthritis Initiative. Ann Rheum Dis 75:1852-7

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