1 The affinity of 17 compounds for muscarine-sensitive acetylcholine receptors in atrial pacemaker cells and ileum of the guinea-pig has been measured at 290C in Ringer-Locke solution. Measurements were also made at 370C with 7 of them. 2 Some of the compounds had much higher affinity for the receptors in the ileum than for those in the atria. For the most selective compound, 4-diphenylacetoxy-N-methylpiperidine methiodide, the difference was approximately 20-fold. The receptors in the atria are therefore different in structure from those in the ileum. 3 The effects of temperature on affinity are not the same for all the compounds tested, indicating different enthalpies and entropies of adsorption and accounting for some of the difficulty experienced in predicting the affinity of new compounds.
ABSTRACT:We have modified the techniques of Lindstrom and of Tindall to measure serum acetylcholine receptor antibody using human antigen bound to l25 I-alpha Bungarotoxin. By using 10 \xA of serum and precipitating antigen-antibody complexes with an excess of staph A, we found that only one out of 43 patients with clinically diagnosed active generalized Myasthenia Gravis had no antibodies. In pooling these results with the results of tests done for diagnostic purposes we found positive results in 54/55 generalized active MG, 8/21 MG in remission, 16/37 ocular MG and 0/55 healthy controls. Two out of 38 non MG were also positive and their clinical diagnosis of botulism and penicillamine treated rheumatoid arthritis have been confirmed by a one year follow-up. Most of these sera were also tested for reactivity with fetal calf AchR. Six out of 49 samples positive with the human receptor were negative with calf receptor. We conclude that our technique is extremely useful for the diagnosis of Myasthenia Gravis and that fetal calf antigen cannot replace human antigen in the assay. RESUME: Les anticorps diriges contre les recepteurs a ^acetylcholine dans la myasthenic grave. Nous avons modifie le test diagnostique serologique tel que decrit par Lindstrom et Tindal pour mesurer dans le serum les anticorps dirig6s contre les recepteurs a ['acetylcholine. Le recepteur a ('acetylcholine d'origine humaine marque avec de l'alpha Bungarotoxine iodee est incube avec 10 ml de serum a tester. Apres incubation les complexes immuns sont p r e c i p e s par un exces de staphylocoque A. Parmi 43 cas de myasthenic generalisee dument diagnostiques cliniquement nous n'avons retrouve qu'un serum negatif. En additionnant les resultats des tests diagnostiques et en tenant compte de Involution clinique nous avons trouve que le test etait positif chez 54 des 55 malades testes (98 %) ayant une myasthenic generalisee, 8 des 21 (38 %) myasthenics en remission, 16 des 37 (43 %) myasthenics oculaires et aucun des 55 controles. Deux echantillons sur 38 provenant de malades non myastheniques se sont egalement av£res positifs. Dans ces deux cas, les diagnostiques cliniques de polyarthrite rhumatoi'de traitee par penicillamine et de botulisme ont ete confirmes par un suivi clinique de un an. La plupart de ces serums ont aussi 6t6 testes en utilisant un antigene foetal d'origine bovine. Six des 49 malades positifs avec l'antigene humain (12 %) se sont av6res negatifs avec l'antigene bovin. Nous concluons que notre technique augmente la sensibilite du test diagnostique de la myasthenic et que l'antigene foetal d'origine bovine ne peut pas remplacer l'antigene d'origine humaine.
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