{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:15:48Z","timestamp":1777922148817,"version":"3.51.4"},"reference-count":14,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lymphatic Research and Biology"],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lymphedema includes primary lymphedema (P-LE) and secondary lymphedema (S-LE), which is a chronic progressive disease. The former group is further classified as congenital and acquired P-LE (AP-LE); its etiology is unclear, and only a few studies on its pathophysiology exist. We hypothesized that an autoimmune disease or self-inflammatory mechanism occurs in lymphatic vessels, leading to obstruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>We enrolled 46 patients with lymphedema who underwent lymphaticovenous anastomosis (LVA) from January to October 2015. Collecting lymph ducts were obtained during LVA. We performed hematoxylin\/eosin staining and immunostaining for LYVE-1, IL-1\u03b2, IL-6, and TNF-\u03b1. There were no substantial histological differences between the two types of lymphedema, whereas some differences in expression of inflammatory cytokines, including interleukin (IL)-1\u03b2 and tumor necrosis factor (TNF)-\u03b1, were observed. Only a few inflammatory cells could be seen around the vessels. Although no significant differences in expression of IL-1\u03b2 were found between AP-LE and S-LE, TNF-\u03b1 was more highly expressed in the smooth muscle layer in AP-LE patients than in S-LE patients. There were no significant morphological differences in the collecting ducts of lymphatic vessels between S-LE and P-LE. Nevertheless, higher levels of TNF-\u03b1 accumulation were found in the thick smooth muscle layer of P-LE patients than in that of S-LE patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>TNF-\u03b1-related inflammation in collecting ducts of lymphatic vessels is an important characteristic of the pathology of P-LE. TNF-\u03b1 inhibitors might improve symptoms of AP-LE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/lrb.2019.0046","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T10:53:58Z","timestamp":1574333638000},"page":"232-238","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Preliminary Report: The Relevance of Tumor Necrosis Factor-\u03b1 in Acquired Primary Lymphedema\u2014A Histopathological Investigation"],"prefix":"10.1177","volume":"18","author":[{"given":"Saori","family":"Asano","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taro","family":"Mikami","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiro","family":"Maegawa","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Wakui","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouichi","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryusuke","family":"Yoshimi","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X15620852"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00727-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358836X9800300209"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/303019"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/316915"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/375614"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041126"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13482"},{"key":"e_1_3_4_10_2","first-page":"19","article-title":"Effect of complex decongestive physiotherapy on gene expression for the inflammatory response in peripheral lymphedema","volume":"33","author":"Foldi E","year":"2000","unstructured":"Foldi E, , Sauerwald A, , Hennig B. Effect of complex decongestive physiotherapy on gene expression for the inflammatory response in peripheral lymphedema. Lymphology, 2000; 33:19\u201323.","journal-title":"Lymphology"},{"key":"e_1_3_4_11_2","first-page":"7","article-title":"Tumor necrosis factor receptors in lymphoid tissues and lymphomas. Source and site of action of tumor necrosis factor alpha","volume":"139","author":"Ryffel B","year":"1991","unstructured":"Ryffel B, , Brockhaus M, , Durmuller U, , Gudat F. Tumor necrosis factor receptors in lymphoid tissues and lymphomas. Source and site of action of tumor necrosis factor alpha. Am J Pathol, 1991; 139:7\u201315.","journal-title":"Am J Pathol"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-008-0006-1"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-009-1259-z"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080453"},{"key":"e_1_3_4_15_2","first-page":"1717","article-title":"Therapeutic effect of ulinastatin on pulmonary fibrosis via downregulation of TGFbeta1, TNFalpha and NFkappaB","volume":"17","author":"Li D","year":"2018","unstructured":"Li D, , Ji H, , Zhao B, , Xu C, , Xia W, , Han L, , Yu D, , Ju Y, , Jin C. Therapeutic effect of ulinastatin on pulmonary fibrosis via downregulation of TGFbeta1, TNFalpha and NFkappaB. Mol Med Rep, 2018; 17:1717\u20131723.","journal-title":"Mol Med Rep"}],"container-title":["Lymphatic Research and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/lrb.2019.0046","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/lrb.2019.0046","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/lrb.2019.0046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:12:46Z","timestamp":1777666366000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/lrb.2019.0046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":14,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,6,1]]}},"alternative-id":["10.1089\/lrb.2019.0046"],"URL":"https:\/\/doi.org\/10.1089\/lrb.2019.0046","relation":{},"ISSN":["1539-6851","1557-8585"],"issn-type":[{"value":"1539-6851","type":"print"},{"value":"1557-8585","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]}}}