Since the blood and thymus of patients with myasthenia gravis may contain inhibitors of neuromuscular transmission that affect acetylcholine receptors of striated muscle, we used denervated rat muscle to test for inhibitors in 43 serums and 18 thymus glands from such patients. Seven per cent of serums inhibited the binding of 125l alpha-bungarotoxin to triton-solubilized receptors; 65 per cent interfered with binding of toxin-labeled receptors to concanavalin-A coupled to Sepharose gel, and 85 per cent formed IgG-receptor complexes detectable by immunoprecipitation. Serum inhibitory activity varied widely among patients with similar clinical manifestations and was not correlated with duration of myasthenia gravis or thymectomy. Among thymus extracts, 44 per cent were inhibitory in the concanavalin-A binding assay, whereas 72 per cent contained anti-receptor IgG. Thus, serums from patients with myasthenia gravis contain more than one anti-receptor factor.
The meta-and para-substituted syu-benzaldoxime arenesulfonates were prepared fro111 the reaction between the sodium salt of the osime and the acid chloride in absolute ether. These osime esters reacted in aqueous alcohol readily to yield the corresponding nitriles exclusively. The reaction rates can be correlated by a I-Iammett plot with a slope of -0.77. Several parasubstituents tended to deviate fro111 the line. Isotope study gives a krr/k~ ratio of 4.51. The rate was found to be sensitive to the change in the ionizing power of the solvent, and to the change in the strength of the esterifying acid. The addition of lithiurn perchlorate gives rise to a nornlal salt effect. S o d i~~n~ acetate brings about a basic elimination having a Hamrnett p value of +0.44. A mechanism is proposed in the light of these results.
Substituted syn-benzaldoxime esters are transformed, in an alcoholic solution, to the corresponding nitriles according to first-order kinetics. All ortho substituents were observed to accelerate the rate of nitrile formation relative to the corresponding para derivative. \\ihile the k,/k, ratios for the bromo, chloro, fluoro, methoxy, and methyl substituents fall within the range of 2 t o 9, the iodo and methylthio substituents are 119 and 11 000 respectively. Isotopic replacement of the aldoximino hydrogen by deuterium gives rise to a kinetic isotope effect, k~/ k~ being 5.21 for syn-o-chlorobenzaldoxime p-toluenesulfonate, 1.22 for syn-o-iodobenzaldoxime p-toluenesulfonate, and 1.23 for syn-o-methylthiobenzaldoxilne o-iodobenzoate. The marked enhancement of rate and the absence of an appreciable isotope effect are considered to be associated with sulfur and iodine participation in the rate-determining step. X mechanism which is capable of explaining the results observed is suggested.
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