Purified Fab fragments of digoxin-specific antibodies obtained from sheep were used to treat 26 patients with advanced, life-threatening digoxin (23 cases) or digitoxin (3 cases) toxicity. These patients had advanced cardiac arrhythmias, and in some cases hyperkalemia, which were resistant to conventional treatment. All patients had an initial favorable response to doses of Fab fragments calculated (in most cases) to be equivalent, on a molar basis, to the amount of cardiac glycoside in the patient's body. In four patients treated after prolonged hypotension and low cardiac output, death ensued from cerebral or myocardial hypoperfusion. In one case the available Fab fragment supply was inadequate to reverse a massive suicidal ingestion of digoxin, and the patient died after recurrent ventricular arrhythmias. In the remaining 21 patients, cardiac rhythm disturbances and hyperkalemia were rapidly reversed, and full recovery ensued. There were no adverse reactions to the treatment. We conclude that the use of purified digoxin-specific Fab fragments is a safe and effective means to reverse advanced, life-threatening digitalis intoxication.

SummaryPlasma membrane serotonin transporters (SERTs) regulate serotonin (5HT) levels in brain and are a site of action of antidepressants and psychostimulant drugs of abuse. Syntaxin 1A is a component of the synaptic vesicle docking and fusion apparatus and has been shown to interact with multiple plasma membrane neurotransmitter transporters including SERT. Previously we showed that syntaxin 1A regulates the transport stoichiometry of SERT. When not bound to syntaxin 1A, SERT shows both substrate-independent Na + fluxes and substrate-dependent Na + fluxes of variable stoichiometry; these fluxes are eliminated in the presence of syntaxin 1A as Na + flux becomes strictly coupled to 5HT uptake. However, not known are the endogenous signaling molecules that determine the conducting states that SERT exhibits. In the present experiments, we show that inhibitors of calcium/calmodulin-dependent kinase II (CaM kinase II) modulate the stoichiometry of 5HT flux and that this effect requires syntaxin 1A. The modulation correlates with a shift in the affinity of SERT for syntaxin 1A binding. The regulation by CaM kinase II is eliminated by a mutation in the N-terminal domain of SERT. In neonatal thalomocortical neurons that endogenously express SERT and syntaxin 1A, inhibition of CaM kinase II reveals SERT-mediated currents. These data suggest that calcium-mediated signals can serve as a trigger for regulating protein-protein interactions that control SERT conducting states.

When Azotobacter vinelandii is grown under nitrogen-fixing conditions, the mean cell volume fluctuates from 2.7 to 6.6 pm3 as determined using a Coulter counter. When NH,Cl is supplied as nitrogen source, the mean cell volume fluctuates from 4.6 to 7.4 pm3. Parallel experiments using flow cytometric measurements show similar characteristic fluctuations in the narrow forward angle light scattering signal and also in cellular protein content as determined using fluorescein isothiocyanate (FITC) fluorescence. Fluctuations in the perpendicular light scatter signal during batch growth are similar for both sets of growth conditions. Changes in cell morphology and ultrastructure are also similar for both sets of growth conditions, as demonstrated by electron microscopic examination. We conclude that narrow forward angle light scatter is a close correlate of cell size, whereas right angle scatter is an indicator of morphological variations other than size.

Fluorescein-conjugated rabbit antibodies to formalized spores of Bacillus anthracis were tested against strains of B. anthracis and other Bacillus species in a subjective immunofluorescence test. The lack of reaction of B. anthracis Vollum spores with conjugated antibody raised against B. anthracis Sterne spores indicated that spores of the Vollum strain lacked a major surface antigen present in most of the other anthrax strains tested, including the non-encapsulated strains Sterne and the Soviet ST1, variants cured of the pX01 plasmid that codes for the toxin, and several virulent strains. Four other antibody preparations, raised against B. anthracis Vollum, New Hampshire, Ames and Strain 15, reacted to an approximately similar degree with spores of all four strains and of Sterne, indicating that Vollum has at least one spore antigen in common with these other strains. The anti-Sterne and anti-Vollum conjugates both displayed cross-reactions with spores of strains of B. cereus, B. coagulans, B. subtilis, B. megaterium, B. polymyxa, B. pumilus and B. thuringiensis. Absorption of the anti-anthrax conjugates with B. cereus NCTC 8035 and NCTC 10320 removed all these cross-reactions, demonstrating the existence of spore antigens specific for anthrax.

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