{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:52:25Z","timestamp":1761807145903},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,16]],"date-time":"2004-10-16T00:00:00Z","timestamp":1097884800000},"content-version":"vor","delay-in-days":4247,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1993,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Using in situ hybridization, we studied muscle hiopsy specimens from 4 patients with mitochondrial myoparthy, encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS). Three of the 4 prients with MELAS had a mutation at position 3243 of mitochondrial DNA (mt DNA) in the transfer RNA <jats:sup>leu(UUR)<\/jats:sup> gene, and the other patient had a mutation at position 3271 in the same transfer RNA <jats:sup>leu(UUR)gene<\/jats:sup>. Quantitative analysis using Southern blot hybridization and polymerase chain reaction showed 80 to 90% mutant mtDNA in muscle. In situ hybridization analysis showed that total mtDNAs (both normal and mutant) ware extremely increased in blood vessels with high succinate dehydrogenase activity (strongly succinate dehydrogenase\u2010reactive blood vessels) and ragged\u2010red fibers. Cytochrome oxidase activity in most of these reactive blood vessels and ragged\u2010red fibers was positive. The similar morphological behavior in these vessels and fibers suggests that an increase in mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues where cytochrome <jats:italic>c<\/jats:italic> oxidase is not a primarily defective enzyme. The pattern of expression of genes of mtDNA\u2010encoded ribosomal RNA and the protein coding region cytochrome <jats:italic>c<\/jats:italic> oxidase subunit II were similar in muscle specimens of patients with MELAS, patients with chronic progressive external ophthalmoplegia, and normal control subjects, and also between the two MELAS mutations. These results do not support the hypothesis that impaired transcription termination is a molecular defect in MELAS.<\/jats:p>","DOI":"10.1002\/ana.410330308","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T14:33:47Z","timestamp":1104590027000},"page":"275-280","source":"Crossref","is-referenced-by-count":42,"title":["Increased mitochondrial DNA in blood vessels and ragged\u2010red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS)"],"prefix":"10.1002","volume":"33","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":"Ryoichi","family":"Sakuta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuya","family":"Nonaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shukuro","family":"Araki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170602"},{"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":"10.1001\/archopht.1958.00940080296016"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(80)90031-3"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198905183202001"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90059-N"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/348651a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(91)90042-8"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.13.11.919"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(89)90136-6"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.23.9509"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90238-A"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688185"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410250611"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410290606"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/351236a0"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.3.561"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2448875"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90418-9"},{"key":"e_1_2_1_22_2","first-page":"934","article-title":"The mitochondrial tRNALeu(UUR) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, bio\u2010chemical, and morphological correlations in skeletal muscle","volume":"50","author":"Moraes CT","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.545"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(83)90125-9"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.2.480"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.410330308","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.410330308","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T23:13:59Z","timestamp":1698189239000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.410330308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,3]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1993,3]]}},"alternative-id":["10.1002\/ana.410330308"],"URL":"https:\/\/doi.org\/10.1002\/ana.410330308","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,3]]}}}