{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T12:32:28Z","timestamp":1758630748340},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":7802,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1985,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>5\u2010Azacytidine (azaC) has previously been shown to raise Hb F levels in the repeatedly phlebotomized baboon (PCV: around 20%). The administration of tetrahydrouridine (THU), an inhibitor of the enzymatic conversion of azaC to 5\u2010azauridine, made it possible to reduce the amount of azaC and also of 2\u2010deoxy\u20105\u2010azacytidine (d\u2010azaC) by more than 90% and still achieve maximal Hb F elevations. However, the granulocytopenia, usually occurring after 5\u2010azaC, was not altered by the lowering of the dosages in the presence of THU. Thus, the granulocytopenia is not due to 5\u2010azauridine or other catabolic products resulting from deamination. It is also unlikely that it is caused by a direct influence of azaC on RNA since d\u2010azaC also causes granulocytopenia. The persistence of reticulocytosis throughout the treatment with azaC or d\u2010azaC makes it appear likely that the observed increase in Hb F levels to more than 60% of total hemoglobin is not due to a cytotoxic effect on erythropoiesis resulting in a shift of cell populations toward greater immaturity, but to a direct influence of the drug on the regulation of \u03b3 globin chain production.<\/jats:p>","DOI":"10.1002\/ajh.2830180310","type":"journal-article","created":{"date-parts":[[2008,10,17]],"date-time":"2008-10-17T17:02:48Z","timestamp":1224262968000},"page":"283-288","source":"Crossref","is-referenced-by-count":14,"title":["Tetrahydrouridine, cytidine analogues, and hemoglobin F"],"prefix":"10.1002","volume":"18","author":[{"given":"Joseph","family":"Desimone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Heller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Molokie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lemuel","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Zwiers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.14.4428"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198212093072401"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1182\/blood.V62.2.370.370","article-title":"5\u2010azacytidine increases \u03b3\u2010globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia","volume":"62","author":"Ley TJ","year":"1983","journal-title":"Blood"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.15.4842"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1182\/blood.V63.1.201.201","article-title":"Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of Hb F by 5\u2010azacytidine","volume":"63","author":"Torrealba\u2010de\u2010Ron AT","year":"1984","journal-title":"Blood"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198404053101401"},{"key":"e_1_2_1_8_2","first-page":"2166","article-title":"Enhancement by tetrahydrouridine of 1\u2010\u03b2\u2010D\u2010arabinofuranosyl\u2010cytosine (cytarabine) oral activity in L 1210 leukemic mice","volume":"30","author":"Neil GL","year":"1970","journal-title":"Cancer Res"},{"key":"e_1_2_1_9_2","first-page":"459","article-title":"Enhancement by tetrahydrouridine (NSC\u2010112907) of the oral activity of 5\u2010azacytidine (NSG\u2010102816) in L 1210 leukemic mice","volume":"59","author":"Neil GL","year":"1975","journal-title":"Cancer Chemother Rep"},{"key":"e_1_2_1_10_2","first-page":"73A","article-title":"The effectiveness of 5\u2010azacytidine (5\u2010azaC) in increasing Hb F levels is enhanced by inhibition of cytosine deaminase","volume":"62","author":"DeSimone J","year":"1983","journal-title":"Blood"},{"key":"e_1_2_1_11_2","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.1016\/S0021-9258(19)45812-2","article-title":"Cytidine deaminase from Escherichia coli: Purification, properties, and inhibition by the potential transaction states analog 3,4,5,6\u2010tetrahydrouridine","volume":"246","author":"Cohen RH","year":"1983","journal-title":"J Biol Chem"},{"key":"e_1_2_1_12_2","first-page":"413","article-title":"Studies on abnormal hemoglobin I. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation","volume":"6","author":"Singer K","year":"1951","journal-title":"Blood"},{"key":"e_1_2_1_13_2","first-page":"489","volume-title":"Globin Gene Expression and Hematopoietic Differentiation","author":"DeSimone J","year":"1983"},{"key":"e_1_2_1_14_2","first-page":"76A","article-title":"On the mechanism of 5\u2010azacytidine induced Hb F in baboons: comparisons of data obtained from cytosine\u2010arabinoside and 5\u2010azacytidine treatments","volume":"62","author":"Veith R","year":"1983","journal-title":"Blood"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6200940"},{"key":"e_1_2_1_16_2","first-page":"552A","article-title":"Hydroxyurea increases fetal hemoglobin production in sickle cell anemia","volume":"32","author":"Dover G","year":"1983","journal-title":"Clin Res"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1981.tb07213.x"},{"key":"e_1_2_1_18_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1182\/blood.V60.2.519.519","article-title":"Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress","volume":"60","author":"DeSimone J","year":"1982","journal-title":"Blood"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60678-8"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.2830180310","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.2830180310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T19:00:00Z","timestamp":1697828400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.2830180310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1985,3]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1985,3]]}},"alternative-id":["10.1002\/ajh.2830180310"],"URL":"https:\/\/doi.org\/10.1002\/ajh.2830180310","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[1985,3]]}}}