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. 1985 Jun;142(6):797–809.

Myasthenia Gravis—Current Concepts

Christian Herrmann Jr, Jon M Lindstrom, John C Keesey, Donald G Mulder
PMCID: PMC1306182  PMID: 3895751

Abstract

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Associate Professor of Medicine.

Current findings indicate that autoimmune myasthenia gravis is an acquired immune complex disorder of neuromuscular transmission in voluntary striated muscle. There is a break in immunologic tolerance leading to blocking and degradation of acetylcholine receptors, together with widening of the synaptic cleft associated with partial destruction, simplification and shortening of the postjunctional membrane. Thymic hyperplasia and thymoma may be present. A decremental response to nerve-muscle stimulation, blocking and jitter on single-fiber electromyography and circulating antibodies to acetylcholine receptor are detectable in most patients with generalized weakness. Although the cause of this abnormal immunologic mechanism remains to be discovered, anticholinesterases, corticosteroids, immunosuppressants, plasmapheresis or thymectomy (individually or in combination) provide control and better prognosis in most patients.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anholt R., Fredkin D. R., Deerinck T., Ellisman M., Montal M., Lindstrom J. Incorporation of acetylcholine receptors into liposomes. Vesicle structure and acetylcholine receptor function. J Biol Chem. 1982 Jun 25;257(12):7122–7134. [PubMed] [Google Scholar]
  2. Borenstein S., Desmedt J. E. Local cooling in myasthenia. Improvement of neuromuscular failure. Arch Neurol. 1975 Mar;32(3):152–157. doi: 10.1001/archneur.1975.00490450032003. [DOI] [PubMed] [Google Scholar]
  3. Brown L. R., Muhm J. R., Gray J. E. Radiographic detection of thymoma. AJR Am J Roentgenol. 1980 Jun;134(6):1181–1188. doi: 10.2214/ajr.134.6.1181. [DOI] [PubMed] [Google Scholar]
  4. Brunner N. G., Berger C. L., Namba T., Grob D. Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management. Ann N Y Acad Sci. 1976;274:577–595. doi: 10.1111/j.1749-6632.1976.tb47717.x. [DOI] [PubMed] [Google Scholar]
  5. Cawley D. B., Herschman H. R., Gilliland D. G., Collier R. J. Epidermal growth factor-toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. Cell. 1980 Nov;22(2 Pt 2):563–570. doi: 10.1016/0092-8674(80)90366-9. [DOI] [PubMed] [Google Scholar]
  6. Cawley D. B., Simpson D. L., Herschman H. R. Asialoglycoprotein receptor mediates the toxic effects of an asialofetuin-diphtheria toxin fragment A conjugate on cultured rat hepatocytes. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3383–3387. doi: 10.1073/pnas.78.6.3383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Christadoss P., Lennon V. A., Krco C. J., Lambert E. H., David C. S. Genetic control of autoimmunity to acetylcholine receptors: role of Ia molecules. Ann N Y Acad Sci. 1981;377:258–277. doi: 10.1111/j.1749-6632.1981.tb33737.x. [DOI] [PubMed] [Google Scholar]
  8. Claudio T., Ballivet M., Patrick J., Heinemann S. Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1111–1115. doi: 10.1073/pnas.80.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Compston D. A., Vincent A., Newsom-Davis J., Batchelor J. R. Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain. 1980 Sep;103(3):579–601. doi: 10.1093/brain/103.3.579. [DOI] [PubMed] [Google Scholar]
  10. Conti-Tronconi B. M., Hunkapiller M. W., Lindstrom J. M., Raftery M. A. Subunit structure of the acetylcholine receptor from Electrophorus electricus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6489–6493. doi: 10.1073/pnas.79.21.6489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Conti-Tronconi B. M., Raftery M. A. The nicotinic cholinergic receptor: correlation of molecular structure with functional properties. Annu Rev Biochem. 1982;51:491–530. doi: 10.1146/annurev.bi.51.070182.002423. [DOI] [PubMed] [Google Scholar]
  12. Conti-Tronconi B., Tzartos S., Lindstrom J. Monoclonal antibodies as probes of acetylcholine receptor structure. 2. Binding to native receptor. Biochemistry. 1981 Apr 14;20(8):2181–2191. doi: 10.1021/bi00511a017. [DOI] [PubMed] [Google Scholar]
  13. DILLON J. B., SABAWALA P. B. Hypersensitivity of in vitro myasthenic muscle to d-tubocurarine. Neurology. 1959 Jan;9(1):62–64. doi: 10.1212/wnl.9.1.62. [DOI] [PubMed] [Google Scholar]
  14. Dau P. C., Lindstrom J. M., Cassel C. K., Denys E. H., Shev E. E., Spitler L. E. Plasmapheresis and immunosuppressive drug therapy in myasthenia gravis. N Engl J Med. 1977 Nov 24;297(21):1134–1140. doi: 10.1056/NEJM197711242972102. [DOI] [PubMed] [Google Scholar]
  15. Devillers-Thiery A., Giraudat J., Bentaboulet M., Changeux J. P. Complete mRNA coding sequence of the acetylcholine binding alpha-subunit of Torpedo marmorata acetylcholine receptor: a model for the transmembrane organization of the polypeptide chain. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2067–2071. doi: 10.1073/pnas.80.7.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Drachman D. B., Adams R. N., Josifek L. F., Self S. G. Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis. N Engl J Med. 1982 Sep 23;307(13):769–775. doi: 10.1056/NEJM198209233071301. [DOI] [PubMed] [Google Scholar]
  17. Drachman D. B., Angus C. W., Adams R. N., Michelson J. D., Hoffman G. J. Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation. N Engl J Med. 1978 May 18;298(20):1116–1122. doi: 10.1056/NEJM197805182982004. [DOI] [PubMed] [Google Scholar]
  18. Drachman D. B. Myasthenia gravis (first of two parts). N Engl J Med. 1978 Jan 19;298(3):136–142. doi: 10.1056/NEJM197801192980305. [DOI] [PubMed] [Google Scholar]
  19. Dretchen K. L., Morgenroth V. H., 3rd, Standaert F. G., Walts L. F. Azathioprine: effects on neuromuscular transmission. Anesthesiology. 1976 Dec;45(6):604–609. [PubMed] [Google Scholar]
  20. Engel A. G., Lambert E. H., Howard F. M. Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations. Mayo Clin Proc. 1977 May;52(5):267–280. [PubMed] [Google Scholar]
  21. Engel A. G., Lindstrom J. M., Lambert E. H., Lennon V. A. Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model. Neurology. 1977 Apr;27(4):307–315. doi: 10.1212/wnl.27.4.307. [DOI] [PubMed] [Google Scholar]
  22. Engel A. G., Sahashi K., Fumagalli G. The immunopathology of acquired myasthenia gravis. Ann N Y Acad Sci. 1981;377:158–174. doi: 10.1111/j.1749-6632.1981.tb33730.x. [DOI] [PubMed] [Google Scholar]
  23. Engel A. G., Santa T. Histometric analysis of the ultrastructure of the neuromuscular junction in myasthenia gravis and in the myasthenic syndrome. Ann N Y Acad Sci. 1971 Sep 15;183:46–63. doi: 10.1111/j.1749-6632.1971.tb30741.x. [DOI] [PubMed] [Google Scholar]
  24. Engel A. G., Tsujihata M., Lambert E. H., Lindstrom J. M., Lennon V. A. Experimental autoimmune myasthenia gravis: a sequential and quantitative study of the neuromuscular junction ultrastructure and electrophysiologic correlations. J Neuropathol Exp Neurol. 1976 Sep-Oct;35(5):569–587. doi: 10.1097/00005072-197609000-00008. [DOI] [PubMed] [Google Scholar]
  25. Engel W. K., Warmolts J. R. Myasthenia gravis: a new hypothesis of the pathogenesis and a new form of treatment. Ann N Y Acad Sci. 1971 Sep 15;183:72–87. doi: 10.1111/j.1749-6632.1971.tb30743.x. [DOI] [PubMed] [Google Scholar]
  26. Fon G. T., Bein M. E., Mancuso A. A., Keesey J. C., Lupetin A. R., Wong W. S. Computed tomography of the anterior mediastinum in myasthenia gravis. A radiologic-pathologic correlative study. Radiology. 1982 Jan;142(1):135–141. doi: 10.1148/radiology.142.1.7053523. [DOI] [PubMed] [Google Scholar]
  27. Fritze D., Herrman C., Jr, Naeim F., Smith G. S., Walford R. L. HL-A antigens in myasthenia gravis. Lancet. 1974 Feb 16;1(7851):240–242. doi: 10.1016/s0140-6736(74)92548-3. [DOI] [PubMed] [Google Scholar]
  28. Froehner S. C., Douville K., Klink S., Culp W. J. Monoclonal antibodies to cytoplasmic domains of the acetylcholine receptor. J Biol Chem. 1983 Jun 10;258(11):7112–7120. [PubMed] [Google Scholar]
  29. Gomez C. M., Richman D. P., Burres S. A., Arnason B. G., Berman P. W., Fitch F. W. Monoclonal hybridoma anti-acetylcholine receptor antibodies: antibody specificity and effect of passive transfer. Ann N Y Acad Sci. 1981;377:97–109. doi: 10.1111/j.1749-6632.1981.tb33726.x. [DOI] [PubMed] [Google Scholar]
  30. Guy H. R. A structural model of the acetylcholine receptor channel based on partition energy and helix packing calculations. Biophys J. 1984 Jan;45(1):249–261. doi: 10.1016/S0006-3495(84)84152-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. HALVORSEN S. EFFECTS OF HYPOTHALAMIC LESIONS ON THE ERYTHROPOIETIC RESPONSE TO HYPOXIA IN RABBITS. Acta Physiol Scand. 1964 May-Jun;61:1–19. doi: 10.1111/j.1748-1716.1964.tb02938.x. [DOI] [PubMed] [Google Scholar]
  32. Heinemann S., Bevan S., Kullberg R., Lindstrom J., Rice J. Modulation of acetylcholine receptor by antibody against the receptor. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3090–3094. doi: 10.1073/pnas.74.7.3090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Herrmann C., Jr Myasthenia gravis: brief guide to diagnosis and management. Calif Med. 1967 Apr;106(4):275–281. [PMC free article] [PubMed] [Google Scholar]
  34. Herrmann C., Jr, Sabawala P. B., Barker W. F., Dillon J. B. Reappraisal of in vitro muscle biopsy in myasthenia gravis. Ann N Y Acad Sci. 1966 Jan 26;135(1):302–311. doi: 10.1111/j.1749-6632.1966.tb45478.x. [DOI] [PubMed] [Google Scholar]
  35. Herrmann C., Jr The familial occurrence of myasthenia gravis. Ann N Y Acad Sci. 1971 Sep 15;183:334–350. doi: 10.1111/j.1749-6632.1971.tb30763.x. [DOI] [PubMed] [Google Scholar]
  36. Hofmann W. W. Antimyasthenic action of corticosteroids. Arch Neurol. 1977 Jun;34(6):356–360. doi: 10.1001/archneur.1977.00500180050010. [DOI] [PubMed] [Google Scholar]
  37. Horowitz S. H., Krarup C. A new regional curare test of the elbow flexors in myasthenia gravis. Muscle Nerve. 1979 Nov-Dec;2(6):478–490. doi: 10.1002/mus.880020609. [DOI] [PubMed] [Google Scholar]
  38. Janssen R. S., Kaye A. D., Lisak R. P., Schatz N. J., Arger P. A., Savino P. J. Radiologic evaluation of the mediastinum in myasthenia gravis. Neurology. 1983 May;33(5):534–539. doi: 10.1212/wnl.33.5.534. [DOI] [PubMed] [Google Scholar]
  39. Johns T. R. Treatment of myasthenia gravis: long-term administration of corticosteroids with remarks on thymectomy. Adv Neurol. 1977;17:99–122. [PubMed] [Google Scholar]
  40. Kardys E., Hashim G. A. Experimental allergic encephalomyelitis in Lewis rats: immunoregulation of disease by a single amino acid substitution in the disease-inducing determinant. J Immunol. 1981 Sep;127(3):862–866. [PubMed] [Google Scholar]
  41. Keesey J., Bein M., Mink J., Sample F., Sarti D., Mulder D., Herrmann C., Jr, Peter J. B. Detection of thymoma in myasthenia gravis. Neurology. 1980 Mar;30(3):233–239. doi: 10.1212/wnl.30.3.233. [DOI] [PubMed] [Google Scholar]
  42. Keesey J., Buffkin D., Kebo D., Ho W., Herrmann C., Jr Plasma exchange alone as therapy for myasthenia gravis. Ann N Y Acad Sci. 1981;377:729–743. doi: 10.1111/j.1749-6632.1981.tb33771.x. [DOI] [PubMed] [Google Scholar]
  43. Keesey J., Naiem F., Lindstrom J., Roe D., Herrmann C., Jr, Walford R. Acetylcholine receptor antibody titer and HLA-B8 antigen in myasthenia gravis. Arch Neurol. 1982 Feb;39(2):73–77. doi: 10.1001/archneur.1982.00510140007002. [DOI] [PubMed] [Google Scholar]
  44. Kelly J. J., Jr, Daube J. R., Lennon V. A., Howard F. M., Jr, Younge B. R. The laboratory diagnosis of mild myasthenia gravis. Ann Neurol. 1982 Sep;12(3):238–242. doi: 10.1002/ana.410120303. [DOI] [PubMed] [Google Scholar]
  45. Killen J. A., Lindstrom J. M. Specific killing of lymphocytes that cause experimental autoimmune myasthenia gravis by ricin toxin-acetylcholine receptor conjugates. J Immunol. 1984 Nov;133(5):2549–2553. [PubMed] [Google Scholar]
  46. Kistler J., Stroud R. M., Klymkowsky M. W., Lalancette R. A., Fairclough R. H. Structure and function of an acetylcholine receptor. Biophys J. 1982 Jan;37(1):371–383. doi: 10.1016/S0006-3495(82)84685-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Labarca P., Lindstrom J., Montal M. Acetylcholine receptor in planar lipid bilayers. Characterization of the channel properties of the purified nicotinic acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayers. J Gen Physiol. 1984 Apr;83(4):473–496. doi: 10.1085/jgp.83.4.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Labarca P., Lindstrom J., Montal M. The acetylcholine receptor channel from Torpedo californica has two open states. J Neurosci. 1984 Feb;4(2):502–507. doi: 10.1523/JNEUROSCI.04-02-00502.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Lennon V. A., Lambert E. H. Monoclonal autoantibodies to acetylcholine receptors: evidence for a dominant idiotype and requirement of complement for pathogenicity. Ann N Y Acad Sci. 1981;377:77–96. doi: 10.1111/j.1749-6632.1981.tb33725.x. [DOI] [PubMed] [Google Scholar]
  50. Lennon V. A., Seybold M. E., Lindstrom J. M., Cochrane C., Ulevitch R. Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. J Exp Med. 1978 Apr 1;147(4):973–983. doi: 10.1084/jem.147.4.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Lindstrom J. M., Einarson B. L., Lennon V. A., Seybold M. E. Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis. J Exp Med. 1976 Sep 1;144(3):726–738. doi: 10.1084/jem.144.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Lindstrom J. M., Engel A. G., Seybold M. E., Lennon V. A., Lambert E. H. Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies. J Exp Med. 1976 Sep 1;144(3):739–753. doi: 10.1084/jem.144.3.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Lindstrom J. M., Lambert E. H. Content of acetylcholine receptor and antibodies bound to receptor in myasthenia gravis, experimental autoimmune myasthenia gravis, and Eaton-Lambert syndrome. Neurology. 1978 Feb;28(2):130–138. doi: 10.1212/wnl.28.2.130. [DOI] [PubMed] [Google Scholar]
  54. Lindstrom J. M., Seybold M. E., Lennon V. A., Whittingham S., Duane D. D. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology. 1976 Nov;26(11):1054–1059. doi: 10.1212/wnl.26.11.1054. [DOI] [PubMed] [Google Scholar]
  55. Lindstrom J., Anholt R., Einarson B., Engel A., Osame M., Montal M. Purification of acetylcholine receptors, reconstitution into lipid vesicles, and study of agonist-induced cation channel regulation. J Biol Chem. 1980 Sep 10;255(17):8340–8350. [PubMed] [Google Scholar]
  56. Lindstrom J. Autoimmune response to acetylcholine receptors in myasthenia gravis and its animal model. Adv Immunol. 1979;27:1–50. doi: 10.1016/s0065-2776(08)60261-8. [DOI] [PubMed] [Google Scholar]
  57. Lindstrom J., Einarson B. Antigenic modulation and receptor loss in experimental autoimmune myasthenia gravis. Muscle Nerve. 1979 May-Jun;2(3):173–179. doi: 10.1002/mus.880020304. [DOI] [PubMed] [Google Scholar]
  58. Lindstrom J., Einarson B., Merlie J. Immunization of rats with polypeptide chains from torpedo acetylcholine receptor causes an autoimmune response to receptors in rat muscle. Proc Natl Acad Sci U S A. 1978 Feb;75(2):769–773. doi: 10.1073/pnas.75.2.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Lindstrom J., Merlie J., Yogeeswaran G. Biochemical properties of acteylcholine receptor subunits from Torpedo californica. Biochemistry. 1979 Oct 16;18(21):4465–4470. doi: 10.1021/bi00588a003. [DOI] [PubMed] [Google Scholar]
  60. Lindstrom J., Tzartos S., Gullick W. Structure and function of the acetylcholine receptor molecule studied using monoclonal antibodies. Ann N Y Acad Sci. 1981;377:1–19. doi: 10.1111/j.1749-6632.1981.tb33721.x. [DOI] [PubMed] [Google Scholar]
  61. Lindstrom J., Walter B., Einarson B. Immunochemical similarities between subunits of acetylcholine receptors from Torpedo, Electrophorus, and mammalian muscle. Biochemistry. 1979 Oct 16;18(21):4470–4480. doi: 10.1021/bi00588a004. [DOI] [PubMed] [Google Scholar]
  62. Merlie J. P., Heinemann S., Einarson B., Lindstrom J. M. Degradation of acetylcholine receptor in diaphragms of rats with experimental autoimmune myasthenia gravis. J Biol Chem. 1979 Jul 25;254(14):6328–6332. [PubMed] [Google Scholar]
  63. Mertens H. G., Hertel G., Reuther P., Ricker K. Effect of immunosuppressive drugs (azathioprine). Ann N Y Acad Sci. 1981;377:691–699. doi: 10.1111/j.1749-6632.1981.tb33767.x. [DOI] [PubMed] [Google Scholar]
  64. Montal M., Labarca P., Fredkin D. R., Suarez-Isla B. A. Channel properties of the purified acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayer membranes. Biophys J. 1984 Jan;45(1):165–174. doi: 10.1016/S0006-3495(84)84145-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Mulder D. G., Herrmann C., Buckberg G. D. Effect of thymectomy in patients with myasthenia gravis. A sixteen year experience. Am J Surg. 1974 Aug;128(2):202–206. [PubMed] [Google Scholar]
  66. Mulder D. G., Herrmann C., Jr, Keesey J., Edwards H. Thymectomy for myasthenia gravis. Am J Surg. 1983 Jul;146(1):61–66. doi: 10.1016/0002-9610(83)90260-x. [DOI] [PubMed] [Google Scholar]
  67. Nelles M. J., Gill-Pazaris L. A., Nisonoff A. Monoclonal ant-idiotypic antibodies reactive with a highly conserved determinant on A/J serum anti-para-azophenylarsonate antibodies. J Exp Med. 1981 Dec 1;154(6):1752–1763. doi: 10.1084/jem.154.6.1752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Noda M., Furutani Y., Takahashi H., Toyosato M., Tanabe T., Shimizu S., Kikyotani S., Kayano T., Hirose T., Inayama S. Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor. 1983 Oct 27-Nov 2Nature. 305(5937):818–823. doi: 10.1038/305818a0. [DOI] [PubMed] [Google Scholar]
  69. Noda M., Takahashi H., Tanabe T., Toyosato M., Furutani Y., Hirose T., Asai M., Inayama S., Miyata T., Numa S. Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature. 1982 Oct 28;299(5886):793–797. doi: 10.1038/299793a0. [DOI] [PubMed] [Google Scholar]
  70. Noda M., Takahashi H., Tanabe T., Toyosato M., Kikyotani S., Furutani Y., Hirose T., Takashima H., Inayama S., Miyata T. Structural homology of Torpedo californica acetylcholine receptor subunits. Nature. 1983 Apr 7;302(5908):528–532. doi: 10.1038/302528a0. [DOI] [PubMed] [Google Scholar]
  71. OSSERMAN K. E., KAPLAN L. I. Rapid diagnostic test for myasthenia gravis: increased muscle strength, without fasciculations, after intravenous administration of edrophonium (tensilon) chloride. J Am Med Assoc. 1952 Sep 27;150(4):265–268. doi: 10.1001/jama.1952.03680040007002. [DOI] [PubMed] [Google Scholar]
  72. OSSERMAN K. E., TENG P., KAPLAN L. I. Studies in myasthenia gravis; preliminary report on therapy with mestinon bromide. J Am Med Assoc. 1954 Jul 10;155(11):961–965. doi: 10.1001/jama.1954.03690290011004. [DOI] [PubMed] [Google Scholar]
  73. Oosterhuis H. J., van der Geld H., Gfeltkamp T. E. Studies in myasthenia gravis. 2. The relation of some clinical and immunological data. J Neurol Sci. 1967 May-Jun;4(3):417–434. doi: 10.1016/0022-510x(67)90027-5. [DOI] [PubMed] [Google Scholar]
  74. Osserman K. E., Weiner L. B. Studies in myasthenia gravis. Correlation of antibody immunofluorescence with clinical course. N Engl J Med. 1965 Sep 16;273(12):615–620. doi: 10.1056/NEJM196509162731201. [DOI] [PubMed] [Google Scholar]
  75. Ozdemir C., Young R. R. Electrical testing in myasthenia gravis. Ann N Y Acad Sci. 1971 Sep 15;183:287–302. doi: 10.1111/j.1749-6632.1971.tb30759.x. [DOI] [PubMed] [Google Scholar]
  76. Ozdemir C., Young R. R. The results to be expected from electrical testing in the diagnosis of myasthenia gravis. Ann N Y Acad Sci. 1976;274:203–222. doi: 10.1111/j.1749-6632.1976.tb47686.x. [DOI] [PubMed] [Google Scholar]
  77. Patrick J., Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973 May 25;180(4088):871–872. doi: 10.1126/science.180.4088.871. [DOI] [PubMed] [Google Scholar]
  78. Patrick J., Lindstrom J., Culp B., McMillan J. Studies on purified eel acetylcholine receptor and anti-acetylcholine receptor antibody. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3334–3338. doi: 10.1073/pnas.70.12.3334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Patten B. M. Myasthenia gravis: review of diagnosis and management. Muscle Nerve. 1978 May-Jun;1(3):190–205. doi: 10.1002/mus.880010304. [DOI] [PubMed] [Google Scholar]
  80. Perlo V. P., Poskanzer D. C., Schwab R. S., Viets H. R., Osserman K. E., Genkins G. Myasthenia gravis: evaluation of treatment in 1,355 patients. Neurology. 1966 May;16(5):431–439. doi: 10.1212/wnl.16.5.431. [DOI] [PubMed] [Google Scholar]
  81. Pinching A. J., Peters D. K. Remission of myasthenia gravis following plasma-exchange. Lancet. 1976 Dec 25;2(8000):1373–1376. doi: 10.1016/s0140-6736(76)91917-6. [DOI] [PubMed] [Google Scholar]
  82. Raftery M. A., Hunkapiller M. W., Strader C. D., Hood L. E. Acetylcholine receptor: complex of homologous subunits. Science. 1980 Jun 27;208(4451):1454–1456. doi: 10.1126/science.7384786. [DOI] [PubMed] [Google Scholar]
  83. Ramakrishnan S., Houston L. L. Inhibition of human acute lymphoblastic leukemia cells by immunotoxins: potentiation by chloroquine. Science. 1984 Jan 6;223(4631):58–61. doi: 10.1126/science.6318313. [DOI] [PubMed] [Google Scholar]
  84. Rennie D. P., McGregor A. M., Wright J., Weetman A. P., Hall R., Thorpe P. An immunotoxin of ricin A chain conjugated to thyroglobulin selectively suppresses the antithyroglobulin autoantibody response. Lancet. 1983 Dec 10;2(8363):1338–1340. doi: 10.1016/s0140-6736(83)91094-2. [DOI] [PubMed] [Google Scholar]
  85. Reynolds J. A., Karlin A. Molecular weight in detergent solution of acetylcholine receptor from Torpedo californica. Biochemistry. 1978 May 30;17(11):2035–2038. doi: 10.1021/bi00604a001. [DOI] [PubMed] [Google Scholar]
  86. Roses A. D., Olanow C. W., McAdams M. W., Lane R. J. No direct correlation between serum antiacetylcholine receptor antibody levels and clinical state of individual patients with myasthenia gravis. Neurology. 1981 Feb;31(2):220–224. doi: 10.1212/wnl.31.2.220. [DOI] [PubMed] [Google Scholar]
  87. SCHWAB R. S. WIN 8077 in the treatment of sixty myasthenia gravis patients; a twelve-month report. Am J Med. 1955 Nov;19(5):734–736. doi: 10.1016/s0002-9343(55)80017-4. [DOI] [PubMed] [Google Scholar]
  88. Sahashi K., Engel A. G., Linstrom J. M., Lambert E. H., Lennon V. A. Ultrastructural localization of immune complexes (IgG and C3) at the end-plate in experimental autoimmune myasthenia gravis. J Neuropathol Exp Neurol. 1978 Mar-Apr;37(2):212–223. doi: 10.1097/00005072-197803000-00008. [DOI] [PubMed] [Google Scholar]
  89. Sargent P. B., Hedges B. E., Tsavaler L., Clemmons L., Tzartos S., Lindstrom J. M. Structure and transmembrane nature of the acetylcholine receptor in amphibian skeletal muscle as revealed by cross-reacting monoclonal antibodies. J Cell Biol. 1984 Feb;98(2):609–618. doi: 10.1083/jcb.98.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Seybold M. E., Drachman D. B. Gradually increasing doses of prednisone in myasthenia gravis. Reducing the hazards of treatment. N Engl J Med. 1974 Jan 10;290(2):81–84. doi: 10.1056/NEJM197401102900204. [DOI] [PubMed] [Google Scholar]
  91. Seybold M. E., Lindstrom J. M. Myasthenia gravis in infancy. Neurology. 1981 Apr;31(4):476–480. doi: 10.1212/wnl.31.4.476. [DOI] [PubMed] [Google Scholar]
  92. Stanley E. F., Drachman D. B. Effect of myasthenic immunoglobulin on acetylcholine receptors of intact mammalian neuromuscular junctions. Science. 1978 Jun 16;200(4347):1285–1287. doi: 10.1126/science.663610. [DOI] [PubMed] [Google Scholar]
  93. Strauss A. J. Myasthenia gravis, autoimmunity and the thymus. Adv Intern Med. 1968;14:241–280. [PubMed] [Google Scholar]
  94. Suarez-Isla B. A., Wan K., Lindstrom J., Montal M. Single-channel recordings from purified acetylcholine receptors reconstituted in bilayers formed at the tip of patch pipets. Biochemistry. 1983 May 10;22(10):2319–2323. doi: 10.1021/bi00279a003. [DOI] [PubMed] [Google Scholar]
  95. Sumikawa K., Houghton M., Smith J. C., Bell L., Richards B. M., Barnard E. A. The molecular cloning and characterisation of cDNA coding for the alpha subunit of the acetylcholine receptor. Nucleic Acids Res. 1982 Oct 11;10(19):5809–5822. doi: 10.1093/nar/10.19.5809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Toyka K. V., Brachman D. B., Pestronk A., Kao I. Myasthenia gravis: passive transfer from man to mouse. Science. 1975 Oct 24;190(4212):397–399. doi: 10.1126/science.1179220. [DOI] [PubMed] [Google Scholar]
  97. Tzartos S. J., Lindstrom J. M. Monoclonal antibodies used to probe acetylcholine receptor structure: localization of the main immunogenic region and detection of similarities between subunits. Proc Natl Acad Sci U S A. 1980 Feb;77(2):755–759. doi: 10.1073/pnas.77.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Tzartos S. J., Seybold M. E., Lindstrom J. M. Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies. Proc Natl Acad Sci U S A. 1982 Jan;79(1):188–192. doi: 10.1073/pnas.79.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Tzartos S., Langeberg L., Hochschwender S., Lindstrom J. Demonstration of a main immunogenic region on acetylcholine receptors from human muscle using monoclonal antibodies to human receptor. FEBS Lett. 1983 Jul 11;158(1):116–118. doi: 10.1016/0014-5793(83)80688-7. [DOI] [PubMed] [Google Scholar]
  100. Vallera D. A., Ash R. C., Zanjani E. D., Kersey J. H., LeBien T. W., Beverley P. C., Neville D. M., Jr, Youle R. J. Anti-T-cell reagents for human bone marrow transplantation: ricin linked to three monoclonal antibodies. Science. 1983 Nov 4;222(4623):512–515. doi: 10.1126/science.6353579. [DOI] [PubMed] [Google Scholar]
  101. Van de Velde R. L., Friedman N. B. The thymic "myoidzellen" and myasthenia gravis. JAMA. 1966 Oct 17;198(3):287–288. doi: 10.1001/jama.198.3.287. [DOI] [PubMed] [Google Scholar]
  102. Vincent A. Immunology of acetylcholine receptors in relation to myasthenia gravis. Physiol Rev. 1980 Jul;60(3):756–824. doi: 10.1152/physrev.1980.60.3.756. [DOI] [PubMed] [Google Scholar]
  103. Volkman D. J., Ahmad A., Fauci A. S., Neville D. M., Jr Selective abrogation of antigen-specific human B cell responses by antigen-ricin conjugates. J Exp Med. 1982 Aug 1;156(2):634–639. doi: 10.1084/jem.156.2.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Waldor M. K., Sriram S., McDevitt H. O., Steinman L. In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor. Proc Natl Acad Sci U S A. 1983 May;80(9):2713–2717. doi: 10.1073/pnas.80.9.2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. von Reis G., Liljestrand A., Matell G. Treatment of severe myasthenia gravis with large doses of ACTH. Ann N Y Acad Sci. 1966 Jan 26;135(1):409–416. doi: 10.1111/j.1749-6632.1966.tb45487.x. [DOI] [PubMed] [Google Scholar]

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