{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:10:51Z","timestamp":1771027851385,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":3843,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1994,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We examined muscle sections from 3 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS), using single\u2010fiber polymerase chain reaction, histochemistry, and in situ hybridization. Most type 1 ragged\u2010red fibers showed positive cytochrome <jats:italic>c<\/jats:italic> oxidase activity at the subsarcolemmal region, while type 2 ragged\u2010red fibers had little cytochrome <jats:italic>c<\/jats:italic> oxidase activity. However, there was no difference in the amount of total (mutant and wild\u2010type) mitochondrial DNAs (mtDNAs) and the proportion of mutant mtDNA between type 1 and type 2 ragged\u2010red fibers. These observations suggest that mitochondrial proliferation and nuclear factors affect muscle pathology, including cytochrome <jats:italic>c<\/jats:italic> oxidase activity, in MELAS. Total mtDNAs were greatly increased in ragged\u2010red fibers (about 5\u201317 times over those in non\u2013ragged\u2010red fibers). The proportion of mutant mtDNA was significantly higher in ragged\u2010red fibers (88.1 \u00b1 5.5%) than in non\u2013ragged\u2010red fibers (63.2 \u00b1 21.6%). Thus, the amount of wild\u2010type mtDNA as well as mutant mtDNA was increased in ragged\u2010red fibers in MELAS, failing to support the contention of a replicative advantage of mutant mtDNA. The proportion of mutant mtDNA was significantly higher in the strongly succinate dehydrogenase\u2013reactive blood vessels (83.2 + 4.2%) than in non\u2013succinate dehydrogenase\u2013reactive blood vessels (38.8 \u00b1 16.2%). It seems likely that systemic vascular abnormalities involving cerebral vessels lead to the evolution of stroke\u2010like episodes in MELAS.<\/jats:p>","DOI":"10.1002\/ana.410350407","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T16:00:17Z","timestamp":1104595217000},"page":"413-419","source":"Crossref","is-referenced-by-count":44,"title":["Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS)"],"prefix":"10.1002","volume":"35","author":[{"given":"Makoto","family":"Tokunaga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Mita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsufumi","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihide","family":"Kumamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Uchino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuya","family":"Nonaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Ando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1958.00940080296016"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160409"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(80)90031-3"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/331717a0"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90059-N"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/348651a0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"crossref","unstructured":"GotoY NonakaI HoraiS. A new mtDNA mutation associated with mitochondrial myopathy encephalopathy lactic acidosis and stroke\u2010like episodes (MELAS).Biochim Biophys Acta1991;1097:238\u2013240","DOI":"10.1016\/0925-4439(91)90042-8"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.23.9509"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90238-A"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.2.343"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-359"},{"key":"e_1_2_1_14_2","first-page":"934","article-title":"The mitochondrial tRNALeu(UUR) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, biochemical, and morphological correlations in skeletal muscle","volume":"50","author":"Moraes CT","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410330308"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(83)90125-9"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.545"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410290606"},{"key":"e_1_2_1_19_2","first-page":"645","article-title":"Strongly succinate dehydrogenase\u2010reactive blood vessels (SSV) in various neuromuscular diseases","volume":"32","author":"Matsuoka T","year":"1992","journal-title":"Clin Neurol"},{"key":"e_1_2_1_20_2","first-page":"19","volume-title":"Muscle biopsy: a practical approach","author":"Dubowitz V","year":"1985"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.10.4221"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.2.480"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(92)90226-R"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(89)90005-X"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310408"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.23.11164"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.61.070192.005523"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688185"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410250611"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.410350407","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.410350407","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T14:36:05Z","timestamp":1698158165000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.410350407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1994,4]]}},"alternative-id":["10.1002\/ana.410350407"],"URL":"https:\/\/doi.org\/10.1002\/ana.410350407","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4]]}}}