Proposal of pre-borderline neuropathy as a new disease entity and construction of novel ultra-early diagnosis methods for detecting the disease

• Project/Area Number: 18K07452
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: Obayashi Konen 熊本大学, 大学院生命科学研究部(保), 教授 (90361899)
• Co-Investigator(Kenkyū-buntansha): 中村 政明 国立水俣病総合研究センター, その他部局等, 部長 (50399672) ; 増田 曜章 熊本大学, 病院, 助教 (50464459) ; 田崎 雅義 熊本大学, 大学院生命科学研究部(保), 助教 (50613402) ; 植田 光晴 熊本大学, 病院, 教授 (60452885)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 耐糖能異常ニューロパチー / 準境界型ニューロパチー / 耐糖能異常 / ニューロパチー

Outline of Final Research Achievements

It is well known that is characterized by early selective involvement of small nerve fibers. We studied the difference in degree of disability depending on the type of neuron, involvement of oxidative stress in the onset, frequency, and involvement of the central nervous system in the onset in impaired glucose tolerance neuropathy. The density reduction rate of adrenergic neuron in epidermis was higher than that of cholinergic neuron around sweat glands. In addition, there was a correlation between the serum oxidizing power/antioxidant power ratio and the degree of small-fiber neuropathy (p=0.79、r<0.05). The frequency of neuropathy was 21.3% of all impaired glucose tolerance patients. Moreover, a relationship between impaired glucose tolerance neuropathy and the thalamus and posterior horn of the spinal cord was suggested.

Academic Significance and Societal Importance of the Research Achievements

本研究によって得られた、耐糖能異常ニューロパチーにおける①adrenergic neuronとcholinergic neuronとの障害度の差についてのデータ、②発症への酸化ストレスの関与につ
いてのデータ、③発症への中枢神経系の関与についてのデータ、および準境界型ニューロパチーと称すべき病態に関する出現頻度のデータが、今後「耐糖能異常患者に出現する小径線維ニューロパチーの超早期診断法の確立」、「point of no returnを意識した薬物療法の至適開始時期同定」、そして「耐糖能異常患者における小径線維ニューロパチーの発症機序の一部解明」に結びつく可能性は極めて高い。

Research Products

• [Journal Article] ユニークな自律神経障害を呈する疾患: ATTR アミロイドーシス (2021)
  • Author(s): 安東由喜雄、増田曜章、松下博昭、大林光念、植田光晴
  • Journal Title: 自律神経 Volume: 58 Pages: 12-15
  • NAID: 130008025111
  • Peer Reviewed / Open Access
• [Journal Article] Apolipoprotein AI amyloid deposits in the ligamentum flavum in patients with lumbar spinal canal stenosis (2020)
  • Author(s): Tasaki Masayoshi、Okada Masamitsu、Yanagisawa Akihiro、Nomura Toshiya、Matsushita Hiroaki、Ueda Akihiko、Inoue Yasuteru、Masuda Teruaki、Misumi Yohei、Yamashita Taro、Nakamura Takayuki、Miyamoto Takeshi、Obayashi Konen、Ando Yukio、Ueda Mitsuharu
  • Journal Title: Amyloid Volume: 28 Issue: 2 Pages: 1-6
  • DOI: 10.1080/13506129.2020.1858404
  • Peer Reviewed / Open Access
• [Journal Article] Needle-shaped amyloid deposition in rat mammary gland: evidence of a novel amyloid fibril protein (2020)
  • Author(s): Murakami T., Noguchi K., Hachiya N., Kametani F., Tasaki M., Nakaba S., Sassa Y., Yamashita T., Obayashi K., Ando Y., Hamamura M., Kanno T., Kawasako K.
  • Journal Title: Amyloid Volume: 27 Issue: 1 Pages: 25-35
  • DOI: 10.1080/13506129.2019.1675623
  • Peer Reviewed / Open Access
• [Journal Article] Clinical, pathological, and proteomic characteristics of newly diagnosed amyloidosis patients: Experience from a single referral center in Japan (2020)
  • Author(s): Ando Y, Yamashita T, Misumi Y, Nomura T, Sasada K, Okada M, Inoue Y, Masuda T, Ueda A, Takamatsu K, Obayashi K, Matsui H, Naiki H, Ueda M
  • Journal Title: Neurol Clin Neurosci Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] 準境界型ニューロパチーという新疾患概念の提唱と病態に基づく超早期診断法の考案 (2020)
  • Author(s): 大林光念
  • Journal Title: 自律神経 Volume: 57 Pages: 172-175
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of myoelectrical activities of descending colon by electrointestinogram in patients with ATTRm amyloidosis. (2019)
  • Author(s): Obayashi K, Masuda T, Tasaki M, Ando Y, Ueda M.
  • Journal Title: Amyloid Volume: 26 Issue: sup1 Pages: 66-66
  • DOI: 10.1080/13506129.2019.1583184
  • Peer Reviewed
• [Journal Article] Serum diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) in patients with ATTR-PN. (2019)
  • Author(s): Obayashi K, Masuda T, Tasaki M, Ando Y, Ueda M.
  • Journal Title: Amyloid Volume: 26 Issue: sup1 Pages: 65-65
  • DOI: 10.1080/13506129.2019.1583183
  • Peer Reviewed
• [Journal Article] Simple, reliable detection of amyloid in fat aspirates using the fluorescent dye FSB: prospective study in 206 patients. (2019)
  • Author(s): Tasaki M, Milani P, Foli A, Verga L, Obici L, Basset M, Bozzola M, Ferraro G, Nuvolone M, Morbini P, Capello G, Ueda M, Obayashi K, Paulli M, Ando Y, Merlini G, Palladini G, Lavatelli F.
  • Journal Title: Blood Volume: 134 Issue: 3 Pages: 320-323
  • DOI: 10.1182/blood.2019000420
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A novel age-related venous amyloidosis derived from EGF-containing fibulin-like extracellular matrix protein 1 (2019)
  • Author(s): Tasaki M, Ueda M, Hoshii Y, Mizukami M, Matsumoto S, Nakamura M, Yamashita T, Ueda A, Misumi Y, Masuda T, Inoue Y, Torikai T, Nomura T, Tsuda Y, Kanenawa K, Isoguchi A, Okada M, Matsui H, Obayashi K, Ando Y.
  • Journal Title: The Journal of Pathology Volume: 247 Issue: 4 Pages: 444-455
  • DOI: 10.1002/path.5203
  • Peer Reviewed
• [Journal Article] Natural history and long-term effects of variant protein reduction in non-V30M ATTR amyloidosis. (2019)
  • Author(s): Yamashita T, Ueda M, Nomura T, Okazaki T, Okada M, Tsuda Y, Inoue Y, Masuda T, Misumi Y, Takamatsu K, Obayashi K, Inomata Y, Hibi T, Ando Y.
  • Journal Title: Neurology Volume: 93 Issue: 16 Pages: 714-716
  • DOI: 10.1212/wnl.0000000000008320
  • Peer Reviewed
• [Journal Article] Evaluation of myoelectrical activities of descending colon by electrointestinogram in patients with ATTRm amyloidosis (2019)
  • Author(s): Obayashi K, Masuda T, Tasaki M, Ando Y, Ueda M
  • Journal Title: Amyloid Volume: in press
  • Peer Reviewed
• [Journal Article] Serum diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) in patients with ATTR-PN. (2019)
  • Author(s): Obayashi K, Masuda T, Tasaki M, Ando Y, Ueda M
  • Journal Title: Amyloid Volume: in press
  • Peer Reviewed
• [Journal Article] Teaching NeuroImages: Morphology of lumbosacral dorsal root ganglia and plexus in hereditary transthyretin amyloidosis (2018)
  • Author(s): Masuda T, Ueda M, Kitajima M, Morita K, Misumi Y, Yamashita T, Obayashi K, Yamashita Y, Ando Y
  • Journal Title: Neurology Volume: 91 Issue: 19
  • DOI: 10.1212/wnl.0000000000006474
  • Peer Reviewed / Open Access
• [Presentation] 経皮的大腸電図指標と血液生化学的指標を組み合わせたATTRvアミロイドーシスの超早期診断 (2020)
  • Author(s): 大林光念、田畑有梨、村上華純、田崎雅義、増田曜章、植田光晴
  • Organizer: 第60回日本臨床化学会年次学術集会
• [Presentation] 準境界型ニューロパチーという新疾患概念の提唱と病態に基づく超早期診断法の確立 (2019)
  • Author(s): 大林光念, 増田曜章, 安東由喜雄
  • Organizer: 第72回日本自律神経学会総会 (教育講演)
  • Invited
• [Presentation] Serum diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) in patients with ATTR-PN (2018)
  • Author(s): Obayashi K, Masuda T, Yanagisawa Y, Izaki A, Sonoda Y, Tasaki M, Ueda M, Ando Y
  • Organizer: The XV International Symposium on Amyloidosis
  • Int'l Joint Research
• [Presentation] Evaluation of myoelectrical activities of descending colon by electrointestinogram in patients with ATTRm amyloidosis (2018)
  • Author(s): Sonoda Y, Obayashi K, Masuda T, Izaki A, Yanagisawa Y, Tasaki M, Ando Y Ueda M
  • Organizer: The XV International Symposium on Amyloidosis
  • Int'l Joint Research
• [Remarks] 熊本大学大学院保健学教育部・医学部保健学科
  • URL: http://www.hs.kumamoto-u.ac.jp/
• [Remarks] 熊本大学大学院 生命科学研究部 (保健学系) 構造機能解析学分野 大林研究室
  • URL: http://kumamoto-kouzoukaiseki.com/