Abstract

The overall objective of this project is the application of basic immunochemical techniques to problems of clinical medicine.
The specific aims of the project include: further characterization of the pharmacokinetic effects, metabolism and clinical efficacy of Fab fragments of digoxin-specific antibodies; the use of a radioimmunoassay for dihydrodigoxin, an active digoxin metabolite, in studies of the metabolic conversion of digoxin to dihydrodigoxin in man; the experimental characterization of the basis for a clinically important interaction between quinidine and digoxin in man; the application of a propranolol radioimmunoassay to the study of serum concentrations of this beta-adrenergic drug in patients with cardiovascular disease; the continued development of new radioimmunoassay methods for the measurement of serum concentrations of other important molecules in health and various disease states; the use of antibodies specific for fragments of human fibrinogen in characterizing the action of proteolytic enzymes on fibrinogen in various immunological disorders of man; the development of quantitative immunochemical methods for determining the extent of monocyte contamination in supposedly pure human lymphocyte preparations; and, studies of the human cells and cell products involved in the modulation of the immunological response in man.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL010608-20
Application #
3334357
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1978-12-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
20
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

Matsukawa, M; Mukai, T; Akizawa, T et al. (1998) Isolation and characterization of novel endogenous digitalis-like factors in the ovary of the giant toad, Bufo marinus. J Nat Prod 61:1476-81
Morris, J F; Ismail-Beigi, F; Butler Jr, V P et al. (1997) Ouabain-sensitive Na+,K(+)-ATPase activity in toad brain. Comp Biochem Physiol A Physiol 118:599-606
Matsukawa, M; Akizawa, T; Ohigashi, M et al. (1997) A novel bufadienolide, marinosin, in the skin of the giant toad, Bufo marinus. Chem Pharm Bull (Tokyo) 45:249-54
Butler Jr, V P; Morris, J F; Akizawa, T et al. (1996) Heterogeneity and lability of endogenous digitalis-like substances in the plasma of the toad, Bufo marinus. Am J Physiol 271:R325-32
Matsukawa, M; Akizawa, T; Morris, J F et al. (1996) Marinoic acid, a novel bufadienolide-related substance in the skin of the giant toad, Bufo marinus. Chem Pharm Bull (Tokyo) 44:255-7
Butler Jr, V P; Odel, J G; Rath, E et al. (1995) Digitalis-induced visual disturbances with therapeutic serum digitalis concentrations. Ann Intern Med 123:676-80
Weber, C J; Kim, D; Costanzo, M et al. (1994) Relationships of Na+ and K+ concentrations to GRP, CGRP, and calcitonin immunoreactivities and Na+,K(+)-ATPase (NKA) inhibitory activity in human breast cyst fluid. Ann Surg Oncol 1:339-44
Antman, E M; Wenger, T L; Butler Jr, V P et al. (1990) Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study. Circulation 81:1744-52
Mathan, V I; Wiederman, J; Dobkin, J F et al. (1989) Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Gut 30:971-7
Alam, A N; Saha, J R; Dobkin, J F et al. (1988) Interethnic variation in the metabolic inactivation of digoxin by the gut flora. Gastroenterology 95:117-23

Showing the most recent 10 out of 15 publications