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.
|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|
|Kieval, R S; Butler Jr, V P; Derguini, F et al. (1988) Cellular electrophysiologic effects of vertebrate digitalis-like substances. J Am Coll Cardiol 11:637-43|
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