{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T13:05:09Z","timestamp":1782997509934,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":6278,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1987,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The autoimmune origin of the Lambert\u2010Eaton myasthenic syndrome (LEMS) was documented by passive transfer of its electrophysiological features from humans to mice with IgG. Freeze\u2010fracture electron microscopy has demonstrated a loss of active\u2010zone particles in human LEMS and in its mouse passive transfer model. These data imply that the active zones are targets of the pathogenic LEMS autoantibodies. Immunolocalization of the antibodies has been hindered, however, by a paucity of active\u2010zone particles (about 50\/\u03bcm<jats:sup>2<\/jats:sup> normally and still lower in LEMS) and by diffusion artifacts in the immunoperoxidase method. To obviate these problems, we employed sensitive avidin\u2013biotin detection systems, both peroxidase and ferritin labels, and quantitative immunoelectron microscopy and end\u2010plate morphometry. We compared mice treated with LEMS IgG, control IgG, and no IgG. In all mice, nonspecific background staining was found in the basal lamina covering the muscle fibers and Schwann cells. When a single 10\u2010mg dose of IgG was injected intravenously, IgG samples from 12 patients produced significant immunostaining of the mouse active zones; from 7 patients they did not. Higher doses of intraperitoneally injected IgG (20 mg, three times a day for 2 days, or 10 mg\/day for 15 days) from each of 4 patients (3 of whose IgG previously transferred LEMS to mice) caused significant immunostaining of mouse active zones: (1) the mean density (no.\/\u03bcm presynaptic membrane length) of positive active zones was 0.91 in the immunoferritin study and 0.72 in the immunoperoxidase study (control values, 0.12 and 0.02); and (2) 43% of the ferritin particles in the primary cleft were concentrated at the active zones and the rest were scattered randomly (control value, 5.3%). The findings indicate that LEMS IgG binds to the active zones of the presynaptic membrane.<\/jats:p>","DOI":"10.1002\/ana.410220204","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T17:49:37Z","timestamp":1104601777000},"page":"200-211","source":"Crossref","is-referenced-by-count":62,"title":["Lambert\u2010Eaton myasthenic syndrome: II. Immunoelectron microscopy localization of IgG at the mouse motor end\u2010plate"],"prefix":"10.1002","volume":"22","author":[{"given":"Tadahiro","family":"Fukuoka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethan","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Newsom\u2010Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/31.7.6304184"},{"key":"e_1_2_1_3_2","first-page":"2346","article-title":"V\u00e9sicules synaptiques et poches au niveau des \u201czones actives\u201d de la jonction neuromusculaire","volume":"271","author":"Couteaux R","year":"1970","journal-title":"C R Seances Acad Sci [D] (Paris)"},{"key":"e_1_2_1_4_2","first-page":"291","article-title":"Les zones sp\u00e9cialis\u00e9es des membranes presynaptiques","volume":"278","author":"Couteaux R","year":"1974","journal-title":"C R Seances Acad Sci [D] (Paris)"},{"key":"e_1_2_1_5_2","first-page":"267","article-title":"Immune complexes (IgG and C3) at the motor end\u2010plate in myasthenia gravis. Ultrastructural and light microscopic localization and electrophysiologic correlations","volume":"52","author":"Engel AG","year":"1977","journal-title":"Mayo Clin Proc"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3002(54)90376-5"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.24.7636"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880050905"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410220203"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1956.tb14351.x"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014943"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)90474-8"},{"key":"e_1_2_1_13_2","first-page":"S21","article-title":"Autoimmunity in the Lambert\u2010Eaton myasthenic syndrome","volume":"5","author":"Lennon VA","year":"1982","journal-title":"Muscle Nerve"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.4.480"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170610"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(85)90062-X"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.410220204","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.410220204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T03:00:19Z","timestamp":1697857219000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.410220204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1987,8]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1987,8]]}},"alternative-id":["10.1002\/ana.410220204"],"URL":"https:\/\/doi.org\/10.1002\/ana.410220204","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[1987,8]]}}}