The elucidation of the signalings of cytoskeletal reorganization involved in the development of HTLV-I-associated myelopathy

• Project/Area Number: 24591267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagasaki University
• Principal Investigator: NAKAMURA Tatsufumi 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (00198219)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Hideki 長崎大学, 病院(医学系), 講師 (10437832)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: HTLV-I関連脊髄症 / HTLV-I / 細胞内骨格再構成 / 細胞内シグナル伝達 / 細胞内ｼｸﾞﾅﾙ伝達

Outline of Final Research Achievements

We investigated the factors involved in the development of HTLV-I-associated
Myelopathy(HAM)from the point of view of cytoskeletal reorganization using the efficiency of intercellular transmission of HTLV-I by co-cultivation with HTLV-I-infected T cell lines and H9/K30 luc reporter cells as an indicator. From our data, it was suggested as bellows: 1) activation of cytoskeletal reorganization by down-regulated intracellular cAMP level in HTLV-I-infected cells in HAM patients. 2) activation of CXCR4 signaling leading to Rap1 activation with activation of cytoskeleton reorganization involved in the heightened transmigrating activity to the tissues in HTLV-I-infected cells in HAM patients.

Research Products

• [Journal Article] Direct infection of primary salivary gland epithelial cells by HTLV-I that induces the niche of the salivary glands of Sjögren’s syndrome patients. (2015)
  • Author(s): Nakamura H, Takahashi Y, Yamamoto-Fukuda T, Horai Y, Nakashima Y, Arima K, Nakamura T, Koji T, Kawakami A.
  • Journal Title: Arthritis Rheumatol. Volume: 67 Issue: 4 Pages: 1096-1106
  • DOI: 10.1002/art.39009
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular cyclic adenosine monophosphate regulates the efficiency of intercellular transmission of human T-lymphotropic virus type I. (2014)
  • Author(s): Nakamura T, Satoh K, Nakamura H, Yamasaki H.
  • Journal Title: Clin Exp Neuroimmunol. Volume: 5 Issue: 2 Pages: 209-215
  • DOI: 10.1111/cen3.12097
  • NAID: 120006986489
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1 associated neurologic disease. (2014)
  • Author(s): Nakamura T, Satoh K, Fukuda T, Kinoshita I, Nishiura Y, Nagasato K, Yamauchi A, Kataoka Y, Nakamura T, Sasaki H, Kumagai K, Niwa M, Noguchi M, Nakamura H, Nishida N, Kawakami A.
  • Journal Title: J Neurovirol. Volume: 20 Issue: 3 Pages: 269-277
  • DOI: 10.1007/s13365-014-0244-8
  • Peer Reviewed
• [Journal Article] HTLV-I virological and histopathological analysis in two cases of anti-centromere-antibody-seropositive Sjögren's syndrome. (2013)
  • Author(s): Hideki Nakamura
  • Journal Title: Modern Rheumatology Volume: 23 Issue: 1 Pages: 133-139
  • DOI: 10.1007/s10165-012-0641-x
  • Peer Reviewed
• [Journal Article] Antibodies against Wnt receptor of muscle-specific tyrosine kinase in myasthenia gravis. (2013)
  • Author(s): Takamori M, Nakamura T, Motomura M.
  • Journal Title: J Neuroimmunol. Volume: 254 Issue: 1-2 Pages: 183-6
  • DOI: 10.1016/j.jneuroim.2012.09.001
  • Peer Reviewed
• [Journal Article] Efficacy of prosultiamine treatment in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: results from an open-label clinical trial. (2013)
  • Author(s): Nakamura T, Matsuo T, Fukuda T, Yamato S, Yamaguchi K, Kinoshita I, Matsuzaki T, Nishiura Y, Nagasato K, Narita-Masuda T, Nakamura H, Satoh K, Sasaki H, Sakai H, Kawakami A.
  • Journal Title: BMC Med Volume: 11 Issue: 1 Pages: 182-182
  • DOI: 10.1186/1741-7015-11-182
  • Peer Reviewed
• [Journal Article] Prosultiamine treatment as new therapeutic strategy in HTLV-I-associated myelopathy/tropical spastic paraparesis. (2013)
  • Author(s): Nakamura T.
  • Journal Title: Clin Exp Neuroimmunol Volume: 4 Issue: 3 Pages: 259-260
  • DOI: 10.1111/cen3.12063
  • Peer Reviewed
• [Presentation] Oral administration of prosultiamine results in symptom improvement in patients with overactive bladder due to HTLV-1-associated myelopathy/tropical spastic paraparesis. (2014)
  • Author(s): Matsuo T, Nakamura T, Ohba K, Miyata Y, Sakai H
  • Organizer: XII International Symposium of HTLV in Brasil
  • Place of Presentation: Sao Pauro, Brasil
  • Year and Date: 2014-12-03
• [Presentation] Perspectives of HAM/TSP treatment. (2014)
  • Author(s): Tatsufumi Nakamura
  • Organizer: XII International Symposium of HTLV-I in Brazil.
  • Place of Presentation: Sao Pauro, Brasil
  • Year and Date: 2014-12-03
  • Invited
• [Presentation] プロスルチアミン経口薬によりHTLV-1関連脊髄症に随伴した過活動膀胱患者の症状は軽快し、尿中バイオマーカーも低下した. (2014)
  • Author(s): 松尾朋博、中村龍文、大庭康司郎、望月保志、宮田康好、酒井英樹
  • Organizer: 第21回日本排尿機能学会
  • Place of Presentation: 岡山コンベンションセンター（岡山市）
  • Year and Date: 2014-09-12
• [Presentation] HTLV-I関連脊髄症に対する新しい治療戦略の開発に向けて. (2014)
  • Author(s): 中村龍文
  • Organizer: 合同シンポジウム「感染と神経免疫」、第19回日本神経感染症学会/第26回日本神経免疫学会
  • Place of Presentation: 金沢歌劇座（石川県）
  • Year and Date: 2014-09-04
  • Invited
• [Presentation] Oral administration of prosultiamine improved the symptoms in patients with overactive bladder associated with HTLV-1-related myelopathy/tropical spastic paraparesis, and also reduced urinary biomarkers. (2014)
  • Author(s): Matsuo T, Nakamura T, Miyata Y, Ohba K, Sakai H
  • Organizer: International Continence Society 2014
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 2014-08-08
• [Presentation] HTLV-I関連脊髄症(HAM)に対する経口プロスルチアミン療法の有効性
  • Author(s): 中村龍文、松尾朋博、福田 卓、酒井英樹、佐藤克也、川上純
  • Organizer: 第54回日本神経学会学術集会
  • Place of Presentation: 東京国際フォーラム、東京
• [Presentation] ポリ硫酸ペントサン治療によるHAM患者下肢運動機能改善と血清sVCAM-1値
  • Author(s): 中村龍文、佐藤克也、福田 卓、川上 純.
  • Organizer: 第25回日本神経免疫学会学術集会
  • Place of Presentation: 海峡メッセ下関、山口
• [Presentation] HTLV-I関連脊髄症(HAM)に対するポリ硫酸ペントサンによる治療成績.
  • Author(s): 中村龍文、福田 卓、木下郁夫、枡田智子、長郷国彦、西浦義博、佐藤克也、川上 純
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] HAMに対する新規治療法ー経口プロスルチアミン療法の有効性ー. シンポジウム3ー新薬開発シンポジウム
  • Author(s): 中村龍文、松尾朋博、福田 卓、山口健太郎、佐々木 均、酒井英樹、川上 純
  • Organizer: 第24回日本神経免疫学会学術集会
  • Place of Presentation: 長野
• [Book] 痙性対麻痺（HAMを含む） 今日の治療指針. (2015)
  • Author(s): 中村龍文
  • Total Pages: 1973
  • Publisher: 医学書院
• [Book] 痙性対麻痺（HAMを含む)、今日の治療指針 2015年版 (2015)
  • Author(s): 中村龍文
  • Publisher: 医学書院
• [Book] HTLV-I関連脊髄症、今日の神経疾患治療指針（第2版） (2013)
  • Author(s): 中村龍文
  • Total Pages: 4
  • Publisher: 医学書院
• [Book] ヒトTリンパ球向性ウイルス脊髄症（HAM）、神経疾患、最新の治療2012-2014 (2012)
  • Author(s): 辻野 彰、中村龍文
  • Total Pages: 3
  • Publisher: 南江堂
• [Patent(Industrial Property Rights)] 排尿障害の予防・治療剤 (2013)
  • Inventor(s): 中村龍文、松尾朋博、酒井英樹
  • Industrial Property Rights Holder: 中村龍文、松尾朋博、酒井英樹
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-06-13
  • Overseas
• [Patent(Industrial Property Rights)] HTLV-I関連脊髄症の予防または治療剤 (2013)
  • Inventor(s): 中村龍文、松本 正
  • Industrial Property Rights Holder: 中村龍文、松本 正
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-18
  • Overseas
• [Patent(Industrial Property Rights)] 排尿障害の予防・治療剤 (2012)
  • Inventor(s): 中村龍文,松尾朋博,酒井英樹
  • Industrial Property Rights Holder: 長崎大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-07-13
  • Overseas
• [Patent(Industrial Property Rights)] HTLV-I関連脊髄症の予防または治療剤 (2012)
  • Inventor(s): 中村龍文
  • Industrial Property Rights Holder: 長崎大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-10-12
  • Overseas