Search for a neuromuscular blocking agent in the blood of patients with myasthenia gravis

Nastuk, William L.; Strauss, A; Osserman, Kermit E.

doi:10.1016/0002-9343(59)90248-7

Cited by 96 publications

(28 citation statements)

References 7 publications

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“…This experimental model may represent a valid approach in clarifying the pathogenesis of human myasthenia gravis and may support the hypothesis that in this illness the impairment of neuromuscular transmission, and probably of the chemoreceptor of the muscle endplate (Johns, Grob & Harvey, 1965;Grob, Namba & Feldman, 1966) may be due to an immunological disturbance (Nastuck & Plescia, 1966;Feltkamp, Van Den Berg-Loonen, Nijenhuis, Engelfriet, Van Rossum, Van Loghem & Oosterhuis, 1974). This is consistent with the presence of neuromuscular blocking agents in the sera of myasthenic patients (Berg, 1953;Nastuck, Strauss & Osserman, 1959;Walker, 1973;Laurent, 1973), with the recent findings that have demonstrated a decreased number of active receptor-sites in myasthenic muscles (Fambrough, Drachman & Satyamurti, 1973) and with the presence in myasthenic subjects of a serum globulin which inhibits the binding of a-bungarotoxin to acetylcholine receptors (Alman, Andrew & Appel, 1974). Recently we have produced in rabbits a muscle relaxation that was longer lasting than that previously obtained, and with more similarities to human myasthenia gravis, by immunizing the animals with a cholinoceptor-rich fraction isolated from Torpedo electric organs (Berti, Clementi, Conti-Tronconi & Omini, 1974 Cohen, Weber, Huchet & Changeux (1972) as reported in detail elsewhere (Clementi, Conti-Tronconi, Berti & Folco, 1976.…”

Section: Introductionsupporting

confidence: 67%

“…This is further substantiated by the recent reports on the possibility of inducing immune flaccid paralysis in rats and guinea-pigs (Heilbronn, personal communication) and monkeys (TarrabHazdai, Aharonov, Silmann & Fuchs, 1975 (Berg, 1953;Nastuck et al, 1959;Walker, 1973;Laurent, 1973) and with a recent finding in these patients of a y-globulin that inhibits the binding of a specific toxin to cholinoceptors (Alman et al, 1974). Furthermore from our experiments it appears that the nicotinic receptor proteins present early in phylogenesis still maintain a close antigenic relationship with the nicotinic receptors of mammals.…”

Section: Discussionmentioning

confidence: 61%

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A Cholinoceptor Antiserum: Its Pharmacological Properties

Berti

Clementi

Conti‐Tronconi

et al. 1976

British J Pharmacology

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I Sera of rabbits immunized against a nicotinic receptor-rich fraction, obtained from the electric organ of Torpedo marmorata, were tested for their pharmacological activity on different in vitro preparations. 2 Sera containing antibodies against the nicotinic receptor blocked neuromuscular transmission in the phrenic-nerve hemidiaphragm preparation without affecting the muscle responses evoked by direct electrical stimulation. Complement inactivated sera were still active. Immune sera, incubated for 15 min with a receptor-rich fraction, lost their activity. 3 The immune sera antagonized the responses elicited by acetylcholine on the frog rectus abdominis. 4 The immune sera tested in vitro decreased the compound action potential evoked in the superior cervical ganglion of the rat by electrical stimulation of the preganglionic nerve. 5 The sera did not show any activity on muscarinic receptors of the guinea-pig ileum preparation. 6 It is concluded that in sera obtained from immunized rabbits a substance is present with curare-like action, and that this activity is probably due to the presence of antibodies against the nicotinic receptor.

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Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 61%

A Cholinoceptor Antiserum: Its Pharmacological Properties

Berti

Clementi

Conti‐Tronconi

et al. 1976

British J Pharmacology

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“…Other evidence suggesting that immune mechanisms might operate in this disease were the in-vitro cytolytic effects of myasthenic sera on frog muscle cells (Nastuk, Strauss & Osserman, 1959), lowered serum complement levels in active phases of myasthenia (Nastuk, Plescia & Osserman, 1960) and the production of -y-globulin by cells of the abnormal germinal-centres in myasthenic thymuses (White & Marshall, 1962). Anti-thyroid antibodies (Feldkamp et al, 1963;Simpson, 1964) and the anti-nuclear and rheumatoid factors (White & Marshall, 1962;Simpson, 1964) have also been found to be increased in series of cases of myasthenia gravis.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous myasthenia gravis and pernicious anaemia: A case report with organ antibody studies

Blecher

Williams

1967

Postgraduate Medical Journal

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“…Therefore, a convenient and fast method is required to induce EAMG. It is difficult to obtain natural AChR, so we considered immunizing animals with artificially synthesized AChR (Nastuk et al, 1959;Patrick and Lindstrom, 1973;Sathasivam, 2008).…”

Section: Introductionmentioning

confidence: 99%

A new method to induce myasthenia gravis models and the protective effect of soluble decay accelerating factors

et al. 2015

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ABSTRACT. It is expensive to induce experimental autoimmune myasthenia gravis (EAMG) by active immunity, and difficult to obtain natural acetylcholine receptor (AChR). We sought a new method of inducing EAMG by immunizing rats with artificially synthesized AChR. The AChR mRNA in TE671 cells was extracted and reverse transcribed. The inclusion body was purified and protein concentration was determined, and the EAMG animal model was used for induction. The serum was extracted from rat blood. The antibody titer was determined using enzyme-linked immunosorbant assay (ELISA). The concentration of decay accelerating factor (DAF) in the rat serum was determined by ELISA, and the metabolism of serum rDAF was determined by western blot. We evaluated the inhibition of rDAF by determining the 50% complement hemolysis unit in the rat serum. The extracellular domain (ECD) nucleotide sequence clone produced by polymerase chain reaction was completely consistent with that in the human gene bank; it was induced by isopropyl β-D-1-thiogalactopyranoside to express the protein after insertion into vector pET16b. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the inclusion body protein was the exact target. The ECD protein was able to bind with mAb35 after dialysis and renaturation, which demonstrated protein activity. The soluble ECD protein was used to immunize rats and obtain the EAMG models. The inhibitory effect of the complement was unsatisfactory owing to high decay rate after rDAF injection into the EAMG models. It is easy to induce the EAMG model by obtaining the AChRTEα1 subunit ECD protein using the substitution method.

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Search for a neuromuscular blocking agent in the blood of patients with myasthenia gravis

Cited by 96 publications

References 7 publications

A Cholinoceptor Antiserum: Its Pharmacological Properties

A Cholinoceptor Antiserum: Its Pharmacological Properties

Simultaneous myasthenia gravis and pernicious anaemia: A case report with organ antibody studies

A new method to induce myasthenia gravis models and the protective effect of soluble decay accelerating factors

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