{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:47:17Z","timestamp":1789602437013,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1998,12,1]],"date-time":"1998-12-01T00:00:00Z","timestamp":912470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anorexigens such as aminorex fumarate and dexfenfluramine are associated with the development of severe pulmonary hypertension (PH), which clinically and histopathologically is considered indistinguishable from idiopathic or primary pulmonary hypertension (PPH). For the current study, we asked whether anorexigen-associated PH is characterized by monoclonal pulmonary endothelial cell proliferation (such as in PPH) or, alternatively, is associated with a polyclonal endothelial cell proliferation as found in secondary PH. Analysis of clonality by the human androgen receptor assay was performed in microdissected endothelial cells of plexiform lesions of two patients with anorexigen-associated PH. The four plexiform lesions of Patient 1 and the six of Patient 2 with anorexigen-associated PH exhibited a monoclonal expansion of pulmonary endothelial cells, with a mean clonality ratio of 0.03 \u00b1 0.01 SE. Our results indicate that appetite suppressant\u2013associated PH is identical to PPH not only in clinical and histopathologic features but also, at a molecular level, in terms of the monoclonal nature of the endothelial cell proliferation. The anorexigens may accelerate the growth of pulmonary endothelial cells in patients with predisposition to develop PPH.<\/jats:p>","DOI":"10.1164\/ajrccm.158.6.9805002","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:51:12Z","timestamp":1365083472000},"page":"1999-2001","source":"Crossref","is-referenced-by-count":61,"title":["Monoclonal Endothelial Cells in Appetite Suppressant\u2013associated Pulmonary Hypertension"],"prefix":"10.1093","volume":"158","author":[{"given":"RUBIN M.","family":"TUDER","sequence":"first","affiliation":[{"name":"Department of Pathology, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, and Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, Colorado; and Department of Histochemistry, Hammersmith Hospital, Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZIVOTIJE","family":"RADISAVLJEVIC","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, and Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, Colorado; and Department of Histochemistry, Hammersmith Hospital, Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KENNETH R.","family":"SHROYER","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, and Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, Colorado; and Department of Histochemistry, Hammersmith Hospital, Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JULIA M.","family":"POLAK","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, and Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, Colorado; and Department of Histochemistry, Hammersmith Hospital, Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NORBERT F.","family":"VOELKEL","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, and Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, Colorado; and Department of Histochemistry, Hammersmith Hospital, Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1998,12,1]]},"reference":[{"key":"2026032709053920600_B1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJM199608293350901","article-title":"Appetite-suppressant drugs and the risk of primary pulmonary hypertension.","volume":"335","author":"Abenhaim","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2026032709053920600_B2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0140-6736(92)90129-Q","article-title":"Pulmonary hypertension and dexfenfluramine.","volume":"339","author":"Atanasoff","year":"1992","journal-title":"Lancet"},{"key":"2026032709053920600_B3","first-page":"537","article-title":"Primary pulmonary hypertension and fenfluramine use.","volume":"70","author":"Brenot","year":"1993","journal-title":"B.M.J."},{"key":"2026032709053920600_B4","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1136\/bmj.283.6296.881","article-title":"Pulmonary hypertension and fenfluramine.","volume":"282","author":"Douglas","year":"1981","journal-title":"B.M.J."},{"key":"2026032709053920600_B5","first-page":"618","article-title":"Ein Fall von chronischer pulmonaler Hypertonie nach Fenfluramineinnhame.","volume":"22","author":"Gaul","year":"1982","journal-title":"Wien. Klin. Wochenschr."},{"key":"2026032709053920600_B6","first-page":"782","article-title":"Chronische pulmonale Hypertonie vask\u00fclaren Ursprungs, plexogene pulmonale Arteriopathie und der Appetiz\u00fcgle Aminorex: Nachlese zu einer Epidemie.","volume":"115","author":"Gurtner","year":"1985","journal-title":"Schweiz. Med. Wochenschr."},{"key":"2026032709053920600_B7","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1183\/09031936.93.03050606","article-title":"Pulmonary hypertension and fenfluramine.","volume":"3","author":"Pouwels","year":"1990","journal-title":"Eur. Respir. J."},{"key":"2026032709053920600_B8","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1164\/ajrccm.155.3.9117009","article-title":"Obesity, dexfenfluramine, and pulmonary hypertension: a lesson not learned.","volume":"155","author":"Voelkel","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709053920600_B9","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1056\/NEJM199708283370904","article-title":"Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine.","volume":"337","author":"Mark","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"2026032709053920600_B10","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1161\/01.CIR.42.6.1163","article-title":"Primary pulmonary hypertension: a pathologic study of the lung vessels in 156 clinically diagnosed cases.","volume":"42","author":"Wagenvoort","year":"1970","journal-title":"Circulation"},{"key":"2026032709053920600_B11","first-page":"275","article-title":"Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension.","volume":"144","author":"Tuder","year":"1994","journal-title":"Am. J. Pathol."},{"key":"2026032709053920600_B12","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1172\/JCI1910","article-title":"Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension.","volume":"101","author":"Lee","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2026032709053920600_B13","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1056\/NEJM199704033361403","article-title":"Monoclonal origin of multicentric Kaposi's sarcoma lesions.","volume":"336","author":"Rabkin","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"2026032709053920600_B14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1126\/science.2889267","article-title":"Clonal analysis of human colorectal tumors.","volume":"238","author":"Fearon","year":"1987","journal-title":"Science"},{"key":"2026032709053920600_B15","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/00000478-199703000-00006","article-title":"Desmoid tumor is a clonal cellular proliferation: PCR amplification of HUMARA for analysis of patterns of X-chromosome inactivation.","volume":"7","author":"Lucas","year":"1997","journal-title":"Am. J. Surg. Pathol."},{"key":"2026032709053920600_B16","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","year":"1992","journal-title":"Am. J. Hum. Genet."},{"key":"2026032709053920600_B17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1056\/NEJM199407213310303","article-title":"Langerhans'-cell histiocytosis (Histiocytosis X): a clonal proliferative disease.","volume":"331","author":"Willman","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"2026032709053920600_B18","first-page":"697","article-title":"Monoclonality of smooth muscle cells in human atherosclerosis.","volume":"151","author":"Murry","year":"1997","journal-title":"Am. J. Pathol."},{"key":"2026032709053920600_B19","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1136\/thx.52.2008.S63","article-title":"Appetite suppressants and pulmonary hypertension.","volume":"52","author":"Voelkel","year":"1997","journal-title":"Thorax"},{"key":"2026032709053920600_B20","first-page":"437","article-title":"Epidemiologische Untersuchungen zum Zusammenhang zwischen Appetiz\u00fcglereinnahme und primar vascul\u00e4rer pulmonaler Hypertonie.","volume":"14","author":"Greiser","year":"1973","journal-title":"Internist (Berl.)"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/6\/1999\/67431716\/ajrccm_158_6_1999.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/6\/1999\/67431716\/ajrccm_158_6_1999.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:06:09Z","timestamp":1774616769000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/158\/6\/1999\/8530265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12,1]]},"references-count":20,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1998,12,1]]},"published-print":{"date-parts":[[1998,12,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.158.6.9805002","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1998,12]]},"published":{"date-parts":[[1998,12,1]]}}}