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臨床検査応用を目指したLC-MS/MS定量測定法の開発と基盤技術の構築

Research Project

Project/Area Number 18K07462
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionChiba University

Principal Investigator

佐藤 守  千葉大学, 医学部附属病院, 特任准教授 (20401002)

Co-Investigator(Kenkyū-buntansha) 野村 文夫  千葉大学, 医学部附属病院, 特任教授 (80164739)
東 達也  東京理科大学, 薬学部薬学科, 教授 (90272963)
小川 祥二郎  東京理科大学, 薬学部薬学科, 講師 (30546271)
西村 基  千葉大学, 医学部附属病院, 講師 (80400969)
松下 一之  千葉大学, 医学部附属病院, 准教授 (90344994)
Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Discontinued (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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臨床化学 / ホルモン / LC/MS/MS / Vitamin D / Estrogen / Androgen / 臨床検査 / 自動化 / LC-MS/MS / 同時定量 / 薬剤反応性 / プロテオーム
Outline of Annual Research Achievements

臨床検査においてステロイドホルモン等の低分子代謝物の測定は抗体を用いた免疫学的測定法(イムノアッセイ)で行われてきた。しかしながら、この方法では 結合タンパク質との解離方法の違いや、使用する抗体によって類似構造体の認識能が異なることから、各施設間で測定値が異なるという問題が起こっている。低 分子代謝物は微細な構造変化でその生理活性が大きく異なることから、正確な測り分けが求められる。これらの問題点から、欧米では早くからLC-MS/MSを用いた 測定の検査応用が進められ、大手検査センターを中心に広く利用されている。実際にアメリカ臨床化学会では例年、発表演題の15%が質量分析を 用いた演題であることからも窺える。これに対し、本邦では全く利用されていないのが現状である。 そこで本研究では、この分野でイオン化効率の悪さから最も測定が難しいとされているビタミンD・エストロゲンとアンドロゲンを対象として、LC-MS/MSを使用 した定量測定法を臨床検査に応用することを第一の目的として、臨床検査において求められる非常に高度な精度・再現性・堅牢性を兼ね備えた測定法・前処理法 を確立するとともに、測定キットの開発を行っている。 現在までにビタミンD・エストロゲンの測定法における論文を報告した。特にエストロゲンの現行イムノアッセイでは抗がん剤投与検体において偽高値を示すことがわかった。アンドロゲンについては測定法の構築・測定の安定性等の検証を終了し論文化を行なっている。 また、測定キットにはキャリブレーター、クオリティーコントロールサンプル、前処理カラム、分析カラム等の様々な構成要素が存在するが、その中でも特に重要 な誘導体化試薬における特許を国内、海外で出願し、製品化を行った。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Research-status Report
  • Research Products

    (26 results)

All 2020 2019 2018

All Journal Article (19 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 18 results,  Open Access: 17 results) Presentation (7 results) (of which Invited: 2 results)

  • [Journal Article] Monoamine Oxidase B rs1799836 G Allele Polymorphism Is a Risk Factor for Early Development of Levodopa-Induced Dyskinesia in Parkinson's Disease.2020

    • Author(s)
      Kakinuma S, Beppu M, Sawai S, Nakayama A, Hirano S, Yamanaka Y, Yamamoto T, Chigusa M, Aisihaer X, Aersilan A, Gao Y, Sato K, Itoga S, Ishige T, Nishimura M, Matsushita K, Satoh M, Nomura F, Kuwabara S, Tanaka T
    • Journal Title

      eNeurologicalSci.

      Volume: 19 Pages: 100239-100239

    • DOI

      10.1016/j.ensci.2020.100239

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An in-house centrifugation and membrane filtration technique for identifying microorganisms from positive blood culture bottles with high identification rates using matrix-assisted laser desorption ionization?Time-of-flight mass spectrometry: A preliminary report2020

    • Author(s)
      Tsuchida Sachio、Murata Syota、Miyabe Akiko、Satoh Mamoru、Takiwaki Masaki、Matsushita Kazuyuki、Nomura Fumio
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Issue: 3 Pages: 266-271

    • DOI

      10.1016/j.jiac.2019.09.017

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Post-transcriptional regulation of BRG1 by FIRΔexon2 in gastric cancer2020

    • Author(s)
      Ailiken Guzhanuer、Kitamura Kouichi、Hoshino Tyuji、Satoh Mamoru、Tanaka Nobuko、Minamoto Toshinari、Rahmutulla Bahityar、Kobayashi Sohei、Kano Masayuki、Tanaka Tomoaki、Kaneda Atsushi、Nomura Fumio、Matsubara Hisahiro、Matsushita Kazuyuki
    • Journal Title

      Oncogenesis

      Volume: 9 Issue: 2 Pages: 26-26

    • DOI

      10.1038/s41389-020-0205-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel caged Cookson‐type reagent toward a practical vitamin D derivatization method for mass spectrometric analyses2019

    • Author(s)
      Seki Masahiko、Sato Makoto、Takiwaki Masaki、Takahashi Koji、Kikutani Yoshikuni、Satoh Mamoru、Nomura Fumio、Kuroda Yutaka、Fukuzawa Seketsu
    • Journal Title

      Rapid Communications in Mass Spectrometry

      Volume: 34 Issue: 7

    • DOI

      10.1002/rcm.8648

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholix toxin, an eEF2 ADP-ribosyltransferase, interacts with Prohibitins and induces apoptosis with mitochondrial dysfunction in human hepatocytes.2019

    • Author(s)
      Yahiro K, Ogura K, Terasaki Y, Satoh M, Miyagi S, Terasaki M, Yamasaki E, Moss J.
    • Journal Title

      Cell Microbiol.

      Volume: 4 Issue: 8

    • DOI

      10.1111/cmi.13033

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of conjugation positions of urinary glucuronidated vitamin D 3 metabolites by LC/ESI‐MS/MS after conversion to MS/MS‐fragmentable derivatives2019

    • Author(s)
      Yoshimura Yusuke、Hibi Ryuichiro、Nakata Akiho、Togashi Moeka、Ogawa Shoujiro、Ishige Takayuki、Satoh Mamoru、Nomura Fumio、Higashi Tatsuya
    • Journal Title

      Biomedical Chromatography

      Volume: - Issue: 7

    • DOI

      10.1002/bmc.4538

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Applications of mass spectrometry in clinical chemistry.2019

    • Author(s)
      Satoh M, Nomura F
    • Journal Title

      Medical Mass Spectrometry

      Volume: 3 Pages: 2-10

    • NAID

      130007897975

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Creatine kinase muscle type specifically interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids2019

    • Author(s)
      Hoshino Fumi、Murakami Chiaki、Sakai Hiromichi、Satoh Mamoru、Sakane Fumio
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 513 Issue: 4 Pages: 1035-1040

    • DOI

      10.1016/j.bbrc.2019.04.097

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urinary carboxylesterase 5A fragment as an early diagnostic marker of cat chronic kidney disease.2019

    • Author(s)
      Maeda H, Kobayashi K, Watanabe T, Satoh M, Nomura F, Sogawa K
    • Journal Title

      Journal of Electrophoresis

      Volume: 63 Pages: 39-45

    • NAID

      130007685672

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] プロテオミクスの臨床応用2019

    • Author(s)
      野村文夫、佐藤守
    • Journal Title

      日本医師会雑誌

      Volume: 147(12) Pages: 2504-2505

    • Related Report
      2018 Research-status Report
  • [Journal Article] Current Status of Proteomic Technologies for Discovering and Identifying Gingival Crevicular Fluid Biomarkers for Periodontal Disease.2018

    • Author(s)
      Tsuchida S, Satoh M, Takiwaki M, Nomura F
    • Journal Title

      Int J Mol Sci

      Volume: 20 Issue: 1 Pages: 86-86

    • DOI

      10.3390/ijms20010086

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-throughput genotyping of GC (vitamin D-binding protein) by melting analysis with locked nucleic acid-incorporating dual hybridization probe for improving mismatch discrimination.2018

    • Author(s)
      Ishige T, Satoh M, Itoga S, Nishimura M, Matsushita K, Nomura F.
    • Journal Title

      Clin Chim Acta

      Volume: 487 Pages: 126-132

    • DOI

      10.1016/j.cca.2018.09.034

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of the biocopolymer preparation system, rapid BACproII kit, for mass-spectrometry-based bacterial identification from positive blood culture bottles by the MALDI Biotyper system.2018

    • Author(s)
      Tsuchida S, Murata S, Miyabe A, Satoh M, Takiwaki M, Ashizawa K, Terada T, Ito D, Matsushita K, Nomura F.
    • Journal Title

      J Microbiol Methods.

      Volume: 152 Pages: 86-91

    • DOI

      10.1016/j.mimet.2018.07.017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Determination of serum carbohydrate-deficient transferrin by a nephelometric immunoassay for differential diagnosis of alcoholic and non-alcoholic liver diseases2018

    • Author(s)
      Nomura F, Kanda T, Seimiya M, Satoh M, Kageyama Y, Yamashita T, Yokosuka O, Kato N, Maruyama K.
    • Journal Title

      Clin Chim Acta

      Volume: 485 Pages: 181-186

    • DOI

      10.1016/j.cca.2018.06.040

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Search for a Novel Allergen in Hen's Egg Allergy Using an IgE Immunoblotting Assay.2018

    • Author(s)
      Sogawa K, Takahashi Y, Shibata Y, Satoh M, Kodera Y, Nomura F, Tanaka T, Sato H, Yamaide F, Nakano T, Iwahashi K, Sugita-Konishi Y, Shimada A, Shimojo N.
    • Journal Title

      Int Arch Allergy Immunol

      Volume: 176 Issue: 3-4 Pages: 189-197

    • DOI

      10.1159/000488144

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] An improved in-house lysis-filtration protocol for bacterial identification from positive blood culture bottles with high identification rates by MALDI-TOF MS.2018

    • Author(s)
      Tsuchida S, Murata S, Miyabe A, Satoh M, Takiwaki M, Matsushita K, Nomura F
    • Journal Title

      Journal of microbiological methods

      Volume: 18 Pages: 1684-1688

    • DOI

      10.1016/j.mimet.2018.03.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Capsular serotyping of Haemophilus influenzae by using matrix-associated laser desorption ionization-time of flight mass?spectrometry.2018

    • Author(s)
      Takeuchi N, Segawa S, Ishiwada N, Ohkusu M, Tsuchida S, Satoh M, Matsushita K, Nomura F
    • Journal Title

      Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

      Volume: 18 Issue: 7 Pages: 300062-66

    • DOI

      10.1016/j.jiac.2018.02.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surveillance evaluation of the standardization of assay values for serum total 25-hydroxyvitamin D concentration in Japan.2018

    • Author(s)
      Ihara H, Kiuchi S, Ishige T, Nishimura M, Matsushita K, Satoh M, Nomura F, Yamashita M, Kitajima I, Tsugawa N, Okano T, Hirota K, Miura M, Totani M, Hashizume N; Nutrition Division, Japan Society of Clinical Chemistry.
    • Journal Title

      Ann Clin Biochem.

      Volume: Epub ahead of print Issue: 6 Pages: 0-0

    • DOI

      10.1177/0004563218765570

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of the Effects of Preanalytical Variables on Serum Peptidome Profiles Following Long-Term Sample Storage.2018

    • Author(s)
      Tsuchida S, Satoh M, Umemura H, Sogawa K, Takiwaki M, Ishige T, Miyabayashi Y, Iwasawa Y, Kobayashi S, Beppu M, Nishimura M, Kodera Y, Matsushita K, Nomura F
    • Journal Title

      Proteomics. Clinical applications

      Volume: 15 Issue: 3 Pages: 47-53

    • DOI

      10.1002/prca.201700047

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] プロテオミクスのUp-to-date2019

    • Author(s)
      佐藤守
    • Organizer
      第66回 日本臨床検査医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 臨床化学におけるLC/MS/MS: 現状と課題2019

    • Author(s)
      佐藤守
    • Organizer
      第31回 日本臨床検査医学会関東・甲信越支部総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 質量分析検査標準化ワーキンググループ(WG)の動向2019

    • Author(s)
      佐藤守
    • Organizer
      第163回 質量分析完済談話会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 臨床化学検査におけるLC-MS/MS: その利点とピットフォール2019

    • Author(s)
      佐藤守
    • Organizer
      質量分析により変貌する臨床検査の最前線2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 質量分析の臨床化学における現状と検査室導入へ向けた問題点2019

    • Author(s)
      佐藤守
    • Organizer
      第36回 日本TDM学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] LC/MS/MSによるビタミンD代謝物・各種ステロイドホルモン測定の臨床検査応用2018

    • Author(s)
      佐藤守
    • Organizer
      日本医用マススペクトル学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 質量分析による定量測定のピットフォール2018

    • Author(s)
      佐藤守
    • Organizer
      日本臨床化学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-01-27  

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