{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:29:46Z","timestamp":1770974986799,"version":"3.50.1"},"reference-count":37,"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":2990,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1996,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS), a maternally inherited disorder, is usually associated with a point mutation in mitochondrial DNA (mtDNA) at position 3,243 in the tRNA<jats:sup>Leu(UUR)<\/jats:sup> gene. To further study the pathogenesis of MELAS, we analyzed tissues from 8 MELAS\u20103,243 patients. Southern blot anlaysis showed an increase in the ratio of mtDNA to nuclear DNA in almost all tissues examined, implying that mitochondrial proliferation is ubiquitous and is not confined to ragged\u2010red fibers in muscle. By northern blot analysis, we demonstrated increased steady\u2010state levels of RNA 19, a polycistronic transcript corresponding to the 16S rRNA + tRNA<jats:sup>Leu(UUR)<\/jats:sup> + ND1 genes (which are contiguous in the mtDNA) in heart, kidney, and musscle. These results provide further evidence that altered mitochondrial nucleic acid metabolism may have pathogenic significance in MELAS.<\/jats:p>","DOI":"10.1002\/ana.410400208","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T14:47:14Z","timestamp":1104590834000},"page":"172-180","source":"Crossref","is-referenced-by-count":54,"title":["Mitochondrial DNA and RNA processing in MELAS"],"prefix":"10.1002","volume":"40","author":[{"given":"Petra","family":"Kaufmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Shanske","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"DiMauro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasutoshi","family":"Koga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Schon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160409"},{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/088307389400900102"},{"key":"e_1_2_1_3_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_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410250611"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/348651a0"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(91)90042-8"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2119"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(94)00079-O"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.2.480"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.10.4221"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310408"},{"key":"e_1_2_1_12_2","first-page":"305","volume-title":"Basic methods in molecular biology","author":"Davis LG","year":"1994"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90059-N"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90418-9"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(87)90254-5"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"10228","DOI":"10.1016\/S0021-9258(18)82194-9","article-title":"Post\u2010transcriptional regulation of the steady\u2010state levels of mitochondrial tRNAs in HeLa cells","volume":"268","author":"King MP","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.11.5367"},{"key":"e_1_2_1_19_2","first-page":"7","volume-title":"Molecular cloning: a laboratory manual","author":"Maniatis T","year":"1989"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-197708000-00015"},{"key":"e_1_2_1_21_2","first-page":"492","article-title":"mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases","volume":"48","author":"Moraes CT","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91294-5"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.10.1663"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1586"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00206080"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711700103"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410330308"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350407"},{"key":"e_1_2_1_29_2","doi-asserted-by":"crossref","unstructured":"MitaS TokunagaM KumamotoT et al. 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