{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:47:37Z","timestamp":1762458457133,"version":"build-2065373602"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T00:00:00Z","timestamp":1118793600000},"content-version":"vor","delay-in-days":4428,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[1993,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke\u2010like episodes) is a clinically devastating disease of children and young adults. The cause of the stroke\u2010like episodes is not known. We have sequenced the mitochondrial DNA (mtDNA) in archival paraffin\u2010embedded material from two cases. In only one of these did the mitochondrial tRNA<jats:sup>Leu(UUR<\/jats:sup>) gene contain the nucleotide 3243 A\u2010to\u2010G mutation that is most commonly responsible for MELAS. In this case, we determined the relative proportion of mutant:wild\u2010type mtDNA in sections of the central nervous system and other tissues by PCR amplification, <jats:italic>P<\/jats:italic>alI digestion, DNA electrophoresis, and scanning densitometry of the ethidium bromide\u2010stained gels. The technique allowed the proportion of mitochondria that contain the mutant genome to be compared with the histological findings in immediately adjacent sections of tissue. The mutant mtDNA was detectable in most tissues, the percentage of mtDNA ranging from barely detectable levels to 78 percent. The relative amount of mutant mtDNA correlated poorly with the distribution of histological lesions, both within the central nervous system and in other tissues examined. The proportion was high in tissues such as liver, kidney, adrenal, and pancreas that appeared histologically normal. Relatively low levels were present in some regions of the central nervous system, such as the occipital lobe, which contained many of the characteristic infarct\u2010like lesions. These observations do not support previous speculation that the distribution of these lesions reflects that of the defective mitochondria. The results emphasize the usefulness of the polymerase chain reaction in correlative histogenetic studies.<\/jats:p>","DOI":"10.1002\/path.1711700103","type":"journal-article","created":{"date-parts":[[2005,6,22]],"date-time":"2005-06-22T12:18:34Z","timestamp":1119442714000},"page":"9-14","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Sequencing and quantitative assessment of mutant and wild\u2010type mitochondrial DNA in paraffin sections from cases of MELAS"],"prefix":"10.1002","volume":"170","author":[{"given":"S.","family":"Love","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A. R.","family":"Nicoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Kinrade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,15]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160409"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/348651a0"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310408"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.545"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(88)90005-6"},{"key":"e_1_2_1_7_2","first-page":"38","article-title":"Clinical and autopsy findings in two cases of MELAS presenting with stroke\u2010like episodes but without clinical myopathy","volume":"12","author":"Nicoll JAR","year":"1993","journal-title":"Clin Neuropathol"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688185"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(89)90112-3"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.10.1663"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.54.2.167"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1991.tb00737.x"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1992.tb00772.x"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90242-D"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/339237a0"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90059-N"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(91)90042-8"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1992.tb00680.x"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1711700103","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.1711700103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:27:38Z","timestamp":1761056858000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.1711700103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,5]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1993,5]]}},"alternative-id":["10.1002\/path.1711700103"],"URL":"https:\/\/doi.org\/10.1002\/path.1711700103","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"type":"print","value":"0022-3417"},{"type":"electronic","value":"1096-9896"}],"subject":[],"published":{"date-parts":[[1993,5]]},"assertion":[{"value":"1992-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1992-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}