{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:16:00Z","timestamp":1787015760438,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,11,27]],"date-time":"2014-11-27T00:00:00Z","timestamp":1417046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Serotonin type 3 receptor (5\u2010\n                      <jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>\n                      <jats:sub>3<\/jats:sub>\n                      R) antagonists are potentially useful therapeutic agents for diarrhea\u2010predominant irritable bowel syndrome (\n                      <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\n                      \u2010D). To identify biomarkers predicting effectiveness of the 5\u2010\n                      <jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>\n                      <jats:sub>3<\/jats:sub>\n                      R antagonist (ramosetron) in\n                      <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\n                      \u2010D.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Irritable bowel syndrome\u2010D Japanese subjects received 2.5 or 5\u00a0\n                      <jats:italic>\u03bc<\/jats:italic>\n                      g of ramosetron once daily for 4\u00a0weeks. Colonic mucosal\n                      <jats:italic>S100A<\/jats:italic>\n                      and tryptophan hydroxylase (\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                      <\/jats:italic>\n                      )\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      expression levels were measured before treatment. Genomic\n                      <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                      was extracted from blood and polymorphisms of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Forty\u2010two patients (27 men and 15 women, mean age 42\u00a0years) with\n                      <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\n                      \u2010D were included for analysis. Improvement of\n                      <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\n                      symptoms was seen in 26 (61.9%). Baseline\n                      <jats:italic>S100A10<\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02) and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02) expression were significantly higher in the ramosetron responders than in the non\u2010responders. The frequencies of the\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      rs4537731G allele in linkage disequilibrium with the\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      rs7130929 T allele (11.5%\n                      <jats:italic>vs<\/jats:italic>\n                      50%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003;\n                      <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\n                      : 12; 95% CI: 2.1\u201369) along with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      rs211105 C allele (3.8%\n                      <jats:italic>vs<\/jats:italic>\n                      43.8%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0003;\n                      <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\n                      : 19; 95% CI: 2.1\u2013181) were significantly lower in the responders than in the non\u2010responders. The mean scores of diarrhea at baseline were significantly higher (5.2\n                      <jats:italic>vs<\/jats:italic>\n                      3.7,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.005) in patients with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      rs211105 T\/T than those with the G allele.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions &amp; Inferences<\/jats:title>\n                    <jats:p>\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">TPH<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      gene polymorphisms and\n                      <jats:italic>S100A10<\/jats:italic>\n                      expression, which correlate with 5\u2010\n                      <jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>\n                      signaling were associated with ramosetron effectiveness in\n                      <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\n                      \u2010D, and may possibly lead to prospective identification of the resistance to treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.12473","type":"journal-article","created":{"date-parts":[[2014,11,27]],"date-time":"2014-11-27T01:36:45Z","timestamp":1417052205000},"page":"82-91","source":"Crossref","is-referenced-by-count":20,"title":["Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea\u2010predominant irritable bowel syndrome: expression of\n                    <i>S100A10<\/i>\n                    and polymorphisms of\n                    <i>\n                      <scp>TPH<\/scp>\n                      1\n                    <\/i>"],"prefix":"10.1111","volume":"27","author":[{"given":"A.","family":"Shiotani","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kusunoki","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Manabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kamada","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine Kawasaki Medical School Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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