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Biomedical subjects

E Haber

Publications and source records attributed to E Haber.

At least 343 records · Page 19Linked to original sources

The isolation of digoxin-specific antibody and its use in reversing the effects of digoxin.

Specific antibodies to digoxin were isolated from antisera of sheep immunized with a digoxin-human serum albumin conjugate. The antibody was purified by adsorption to an immunoadsorbent, synthesized by coupling a ouabain-ribonuclease conjugate to bromoacetyl-cellulose, followed by elution with 25 mM ouabain. Ouabain was dissociated from antibody by denaturation in 6 M guanidine. The renatured antibody bound 1.6 mol of digoxin per mol and had an association constant of 1.6 x 10(8) M(-1). At near-stoichiometric concentrations, either purified antibody to digoxin, or its papain-digested product (Fab-Fc), reversed digoxin-induced: (a) inhibition of (86)Rb transport in human erythrocytes, (b) increase in developed tension in isolated guinea-pig atrial strips, and (c) ventricular tachycardia in intact dogs, and also corrected digoxin-induced automaticity in isolated guineapig atrial strips.

Adsorption↗

A fraction of the ventricular myocardium that has the specificity of the cardiac beta-adrenergic receptor.

The 78,000 x g microsomal fraction of canine ventricular myocardium effected a 20-fold concentration of [(3)H]norepinephrine from a 10(-9) M solution. The [(3)H]norepinephrine bound was displaced by physiologic concentrations of the beta-adrenergic catecholamines isoproterenol, epinephrine, and norepinephrine, in that order, which is the order of effectiveness of their actions on the force and rate of cardiac contraction. Alpha-adrenergic compounds did not displace [(3)H]norepinephrine until concentrations four orders of magnitude greater were reached. The beta-adrenergic blocker propranolol displaced at 10(-6) M, whereas the alpha-adrenergic blocker phentolamine was inactive. Metabolites of the catecholamines did not compete for this binding site. It is concluded that, on the basis of specificity and affinity of binding, these microsomal particles are likely to contain the beta-adrenergic receptor.

Adrenergic alpha-Antagonists↗

Isolation and characterization of structurally homogeneous antibodies from antipneumococcal sera.

Antibodies of sufficient homogeneity for sequence studies were readily obtained in high concentrations from rabbits immunized with pneumococcal vaccines. By taking advantage of slightly differing immunologic specificity for Type III and Type VIII capsular polysaccharides, an antibody with unique electrophoretic mobility could be isolated from serum containing several distinct antibody components by using appropriate cross-reacting immunoadsorbents. A unique sequence for the N-terminal 11 amino acid residues of the light chain of the antibody was found, in contrast to several sequences in the antibody mixture from which this component was isolated. The sequence of a nonimmune light chain pool demonstrates even greater heterogeneity. Chymotryptic peptide maps of the antibody light chain show two unique cysteine-containing variable region peptides not seen in maps of nonimmune light chain pool of the same allotypic specificity as that of the antibody light chain. The experimental approach described here may provide further insight into the structure-function relationship of several homogeneous antibodies of closely related specificity for the same polysaccharide antigen.

Acetates↗

Digoxin intoxication: the relationship of clinical presentation to serum digoxin concentration.

A radioimmunoassay for serum digoxin concentration has been used to study the interrelationships of circulating levels of the drug and various factors in the clinical setting in 48 hospitalized patients with cardiac rhythm disturbances due to digoxin intoxication. 131 patients on maintenance doses of digoxin without toxicity and 48 patients with equivocal evidence of digoxin excess were also studied and compared with the toxic group. Patients with cardiac rhythm disturbances due to digoxin intoxication tended to be older and to have diminished renal function compared with the nontoxic group; body weight, serum potassium concentration, underlying cardiac rhythm, and nature of cardiac disease were not significantly different for the groups as a whole. Despite comparable mean daily digoxin dosages, digoxin intoxicated patients had a mean serum digoxin concentration of 3.7 +/-1.0 (SD) ng/ml, while nontoxic patients had a mean level of 1.4 +/-0.7 ng/ml (P < 0.001), 90% of patients without evidence of toxicity had serum digoxin concentrations of 2.0 ng/ml or less, while 87% of the toxic group had levels above 2.0; the range of overlap between the two groups extended from 1.6 to 3.0 ng/ml. Patients with atrioventricular block as their principal toxic manifestation had a significantly lower mean serum digoxin concentration than those in whom ectopic impulse formation was the chief rhythm disturbance. Patients with equivocal evidence of digoxin excess had received comparable daily maintenance doses of digoxin but had a mean serum concentration of 1.9 +/-0.8 ng/ml, intermediate between those of the nontoxic (P < 0.005) and toxic (P < 0.001) groups. Renal function as judged by mean blood urea nitrogen concentration was also intermediate. The data indicate that knowledge of the serum digoxin concentration, weighed in the clinical context, is useful in the management of patients receiving this drug.

Age Factors↗