{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:58:36Z","timestamp":1792047516499,"version":"4.4.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1982,7]]},"abstract":"<jats:p>In an attempt to stimulate Hb F synthesis in baboons by means other than erythropoietic stress, we considered the possibility that an agent that inhibits methylation of CpG sequences in DNA may be effective. 5-Azacytidine, a cytosine analogue that cannot be methylated, is such an agent. Animals whose packed red cell volume was maintained at approximately 20% by bleeding were given 10 daily intravenous injections of the drug (6 mg\/kg) in 12 days. Hb F levels in these animals started to increase on day 5 of this regimen and peak levels, which were 6-30 times higher than those produced by bleeding alone, occurred 5-7 days after the last dose of the drug. In animals previously identified as genetically \"high\" or \"low\" Hb F responders, the maximal Hb F levels were 70-85% and 35-40% respectively. In dose-response studies 5-azacytidine given daily at 3-4 mg\/kg produced maximal Hb F increases. The drug did not correlate the percentage (number) of Hb F-containing cells (F cells) beyond the maximal number achieved by bleeding alone and thus its main effect was to increase Hb F per F cell. The finding that Hb F synthesis can be modulated to such a high degree by a drug may have therapeutic implications--e.g., in sickle cell anemia, in which stimulation of Hb F synthesis may prevent sickling.<\/jats:p>","DOI":"10.1073\/pnas.79.14.4428","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T03:13:20Z","timestamp":1149045200000},"page":"4428-4431","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":279,"title":["5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons."],"prefix":"10.1073","volume":"79","author":[{"given":"J","family":"DeSimone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Zwiers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1982,7]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.79.14.4428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T11:37:00Z","timestamp":1649849820000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.79.14.4428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1982,7]]},"references-count":0,"journal-issue":{"issue":"14","published-print":{"date-parts":[[1982,7]]}},"alternative-id":["10.1073\/pnas.79.14.4428"],"URL":"https:\/\/doi.org\/10.1073\/pnas.79.14.4428","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1982,7]]},"assertion":[{"value":"1982-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}