{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:54:46Z","timestamp":1792734886232,"version":"4.5.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,2,25]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Parathyroid adenomas, the main cause of primary hyperparathyroidism (PHPT), are thought to result from clonal expansion of tumor cells and to be insensitive to normal calcium feedback due to the loss of the calcium-sensing receptor (CASR). Utilizing flow cytometric analysis to isolate and individually study oxyphil cells, chief cells, and lymphocytes from resected parathyroid tumors and glands, we now report previously unrecognized heterogeneity in these tissues with respect to calcium responsiveness, CASR expression, and clonal origin of parathyroid tumors. Such heterogeneity of parathyroid adenomas likely reflects the complex etiopathogenesis and clinical heterogeneity of PHPT.<\/jats:p>","DOI":"10.1073\/pnas.1319742111","type":"journal-article","created":{"date-parts":[[2014,2,7]],"date-time":"2014-02-07T21:02:57Z","timestamp":1391806977000},"page":"3092-3097","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":56,"title":["Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia"],"prefix":"10.1073","volume":"111","author":[{"given":"Yuhong","family":"Shi","sequence":"first","affiliation":[{"name":"Division of General and Oncologic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Hogue","sequence":"additional","affiliation":[{"name":"Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshana","family":"Dixit","sequence":"additional","affiliation":[{"name":"Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Koh","sequence":"additional","affiliation":[{"name":"Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John A.","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of General and Oncologic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,2,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1991.71.2.371"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.5858\/2008-132-1251-PHACP"},{"key":"e_1_3_3_3_2","first-page":"177","article-title":"PRAD1 (cyclin D1): A parathyroid neoplasia gene on 11q13","volume":"40","author":"Arnold A","year":"1992","unstructured":"A Arnold, et al., PRAD1 (cyclin D1): A parathyroid neoplasia gene on 11q13. Henry Ford Hosp Med J 40, 177\u2013180 (1992).","journal-title":"Henry Ford Hosp Med J"},{"key":"e_1_3_3_4_2","first-page":"2960","article-title":"Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism","volume":"83","author":"Carling T","year":"1998","unstructured":"T Carling, et al., Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism. J Clin Endocrinol Metab 83, 2960\u20132963 (1998).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.1999.00961.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199903000-00007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1743"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198803173181102"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(94)90036-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197709292971304"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02739689"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-102-4-1036"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-56-3-572"},{"key":"e_1_3_3_14_2","first-page":"1598","article-title":"Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism","volume":"81","author":"Kifor O","year":"1996","unstructured":"O Kifor, et al., Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 81, 1598\u20131606 (1996).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1067\/msy.1998.91828"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220240"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0277"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070320210"},{"key":"e_1_3_3_19_2","first-page":"691","article-title":"Functioning oxyphil adenoma of parathyroid gland: An ultrastructural and biochemical study","volume":"92","author":"McGregor DH","year":"1978","unstructured":"DH McGregor, LG Lotuaco, MS Rao, LL Chu, Functioning oxyphil adenoma of parathyroid gland: An ultrastructural and biochemical study. Am J Pathol 92, 691\u2013711 (1978).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_20_2","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen RC","year":"1992","unstructured":"RC Allen, HY Zoghbi, AB Moseley, HM Rosenblatt, JW Belmont, Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 51, 1229\u20131239 (1992).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.15.6848"},{"key":"e_1_3_3_22_2","article-title":"Genetic and epigenetic changes in sporadic endocrine tumors: Parathyroid tumors","author":"Costa-Guda J","year":"2013","unstructured":"J Costa-Guda, A Arnold, Genetic and epigenetic changes in sporadic endocrine tumors: Parathyroid tumors. Mol Cell Endocrinol, 2013).","journal-title":"Mol Cell Endocrinol"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3366"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129139"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.0284"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020177"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1385\/EP:11:1:77"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1303064110"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1319742111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:21:32Z","timestamp":1649805692000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1319742111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,7]]},"references-count":28,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,2,25]]}},"alternative-id":["10.1073\/pnas.1319742111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1319742111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,7]]},"assertion":[{"value":"2014-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}