Search PubMed⌕ Search

Biomedical subjects

J A Simpson

Publications and source records attributed to J A Simpson.

At least 91 records · Page 5Linked to original sources
PubMed1982

alpha-Bungarotoxin binding to the nicotinic acetylcholine receptor is inhibited by two distinct subpopulations of anti-receptor antibodies.

Affinity-purified antibodies to the nicotinic acetylcholine receptor of Torpedo marmorata were fractionated into two populations using a covalently cross-linked receptor-toxin immunosorbent lacking free toxin-binding sites. The population of antibodies which bound to and were subsequently eluted from this resin, and which cannot possibly contain antibodies directed to the toxin-binding site itself, was effective in inhibiting the binding of toxin to receptor in solution. This unequivocally demonstrates that inhibition of toxin binding can be mediated by antibodies which are not directed against the toxin-binding site. A second minor population of antibodies which did not bind to the affinity resin but which did inhibit the binding of toxin to receptor in solution was detected. Two subpopulations of toxin-binding inhibitory antibodies can therefore be distinguished. A clear differentiation should be made in future work describing "anti-toxin site" antibodies between antibodies directly binding to the toxin-binding site and the pseudo-anti-toxin-binding site antibodies described in this report.

Animals↗
PubMed1982

The myasthenic (Eaton-Lambert) syndrome associated with carcinoma. Enzyme induction as a possible mechanism of paraneoplastic syndromes.

A myasthenic syndrome associated with small-cell tumours of the bronchus and with autoimmune diseases (Eaton-Lambert syndrome) has been attributed to diminished probability that a nerve action potential will release acetylcholine (ACh) from terminals of cholinergic nerves (somatic motor and autonomic). This model derives from evidence for reduced quantal content of the transmitter released by a nerve impulse. The test procedure implies certain constancies of postsynaptic response. Abnormal responses to ACh-agonists indicate that receptor response is not normal. It is suggested that all previously described neuromuscular responses are compatible with new model: the subsynaptic apparatus produces excess acetylcholinesterase (AChE) which limits the endplate conductance changes produced by normal output of ACh. This model is supported by earlier ultramicroscopic studies which cannot be accounted for by the contemporary model. It is proposed that enzyme induction by peptide or immunoglobulin may also be responsible for other paraneoplastic syndromes.

Acetylcholine↗
PubMed1982

Electrophysiology of neuromuscular junction disease: an appreciation of the contributions of Edward H. Lambert.

As the muscle fiber action potential is "all or none" and is not of constant voltage recorded in volume from remote electrodes, there are serious limitations on assessment of the "safety factor" for neuromuscular transmission by stimulus-response recording from surface electrodes, or by single fiber EMG. Lambert's use of biopsied intercostal muscle with microelectrode recording of spontaneous and evoked end-plate potentials has permitted more accurate analysis of transmission disorders. His personal and collaborative studies on experimental myasthenia gravis, congenital myasthenic syndromes, amyotrophic lateral sclerosis, and the Lambert-Eaton myasthenic syndrome are reviewed. It is suggested that studies of acetylcholine receptor agonists require reevaluation as indicating inadequacies of present models.

Carcinoma, Bronchogenic↗
PubMed1982

Lack of inter-animal cross-reaction of anti-acetylcholine receptor antibodies at the receptor-binding site as demonstrated by heterologous anti-idiotype antisera: implications for immunotherapy of myasthenia gravis.

Anti-idiotype antisera were raised in rabbits by immunization with purified sheep anti-Torpedo receptor antibodies. The antisera were able specifically to block the binding of receptor to the inducing antibodies but not anti-Torpedo antibodies from other animals of the same, or other, species. Rabbits producing the anti-idiotype sera were not protected from experimental autoimmune myasthenia gravis (EAMG). The implications of these observations for the potential use of anti-idiotype antisera in the treatment of myasthenia gravis are discussed.

Animals↗
PubMed1982

Experimental myasthenia gravis is inhibited by receptor-antireceptor complexes.

Experimental autoimmune myasthenia gravis (EAMG) induced in rabbits by immunisation with purified nicotinic acetylcholine receptor from Torpedo marmorata is a highly reproducible model for the human disease. Pretreatment of experimental animals with immune complexes containing receptor and anti-receptor antibodies suppressed the subsequent induction of EAMG. Animals were protected from the normal severe paralysis. Moreover, antibody levels were reduced by synthesis of antibody rapidly terminated. Possible mechanisms are discussed.

Animals↗
PubMed1982

alpha-Bungarotoxin displacing antibody in myasthenia gravis.

The majority of sera from myasthenic patients cannot precipitate all available receptor-toxin complex even in conditions of a 4,000-fold excess of antibody. This effect was traced to displacement of toxin from the receptor-toxin complex. Pure IgG prepared from the serum of a myasthenic patient was as effective as the original serum in displacing ability. The possible effect of such antibodies on the correlation of antibody titre and disease state is discussed.

Antibody Specificity↗
PubMed1980

Anti-acetylcholine receptor antibody titres in the sera of myasthenia patients treated with plasma exchange combined with immunosuppressive therapy.

Anti-acetylcholine receptor antibody titres have been monitored in the sera of 19 myasthenic patients treated with plasma exchange combined with a three month period of immunosuppressive therapy. In general the post-exchange titres stabilised at below pre-exchange levels for prolonged periods which were associated with clinical improvement. In seven instances recurrence of symptoms occurred and in six of these cases relapse was shown to be associated with a rise in anti-acetylcholine receptor antibody titre.

Acetylcholine↗
PubMed1979

Plasma-exchange combined with immunosuppressive therapy in myasthenia gravis.

Twenty-one patients with myasthenia gravis underwent a course of plasma exchange combined with immunosuppressive therapy. In fifteen there was dramatic clinical improvement which has been maintained for periods up to 19 months. Nine of these patients now take no anticholinesterase drugs. Six patients had a recurrence 3--9 months after the first course but in the three given a second course remissions were again obtained.

Adult↗
PubMed1979

Solanum torvum as a causative agent of enzootic calcinosis in Papua, New Guinea.

Inclusion of dried powdered leaves of Solanum torvum Swartz (collected in Papua, New Guinea) in the diet of rats induced hypercalcaemai rapidly and hyperphosphataemia more slowly; soft tissue calcification was most evident in the kidney and lung. Solanum torvum may be a causative agent of enzootic calcinosis in cattle in Papua, New Guinea.

Animals↗
PubMed1977

Penicillamine-associated myasthenia gravis, antiacetylcholine receptor and antistriational antibodies.

Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody. Eleven cases of rheumatoid arthritis with penicillamine-associated antistriational antibodies have also been observed; in three of these cases there was evidence of myasthenia gravis. These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy.

Acetylcholine↗