脂質メディエーターの臨床検査医学の構築

2012 年度 研究成果報告書

• 研究課題/領域番号: 22249017
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 病態検査学
• 研究機関: 東京大学
• 研究代表者: 矢冨 裕 東京大学, 医学部附属病院, 教授 (60200523)
• 研究期間 (年度): 2010 – 2012
• キーワード: 臨床検査医学

研究概要

第二世代脂質メディエーターとされるスフィンゴシン1-リン酸,リゾホスファチジン酸,リゾホスファチジルセリンなどのリゾリン脂質の機能的役割,代謝機構の解明を基礎として,その測定の臨床検査医学的応用に道筋をつけた

研究成果

• [雑誌論文] Inverse correlations between serum ADAMTS13 levels and systolic blood pressure, pulse pressure, and serum C-reactive protein levels observed at a general health examination in a Japanese population: A cross-sectional study. (2013)
  • 著者名/発表者名: Enooku, K., Kato, R., Ikeda, H., Kurano, M., Kume, Y., Yoshida, H., Ono, T., Aizawa, K., Suzuki, T., Yamazaki, T., and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 421 ページ: 147-151
• [雑誌論文] Plasma lysophosphatidic acid levels and hepatocellular carcinoma (Letter). (2013)
  • 著者名/発表者名: Ikeda, H., Enooku, K., Ohkawa, R., Koike, K., and Yatomi, Y.
  • 雑誌名: Hepatology 巻: 57 ページ: 417-418
• [雑誌論文] Sphingosine1-phosphate release from platelets during clot formation: close correlation between platelet count and serum sphingosine1-phosphate concentration. (2013)
  • 著者名/発表者名: Ono, Y., Kurano, M., Ohkawa, R., Yokota, H., Igarashi, K., Aoki, J., Tozuka, M., and Yatomi, Y.
  • 雑誌名: Lipids HealthDis 巻: 12 ページ: 20
• [雑誌論文] Decrease in circulating autotaxin by oral administration of prednisolone. (2013)
  • 著者名/発表者名: Sumida, H., Nakamura, K., Yanagida, K., Ohkawa, R., Asano, Y., Kadono, T., Tamaki, K., Igarashi, K., Aoki, J., Sato, S., Ishii, S., Shimizu, T., and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 415 ページ: 74-80
• [雑誌論文] H. Higher lipoprotein-associated phospholipase A2 levels are associated with coronary atherosclerosis documented by coronary angiography. (2012)
  • 著者名/発表者名: Dohi, T., Miyauchi, K., Ohkawa, R., Nakamura, K., Thuboi, S., Ogita, M., Miyazaki, T., Nishino, A., Yokoyama, K., Kurata, T., Yatomi, Y., and Daida
  • 雑誌名: Ann. Clin. Biochem 巻: 49 ページ: 527-533
• [雑誌論文] Identification and biochemical characterization of a novel autotaxin isoform, ATXdelta, with a four-amino acid deletion. (2012)
  • 著者名/発表者名: Hashimoto, T., Okudaira, S., Igarashi, K., Hama, K., Yatomi, Y., and Aoki, J.
  • 雑誌名: J. Biochem 巻: 151 ページ: 89-97
• [雑誌論文] Y. Antagonism of sphingosine 1-phosphate receptor 2 causes a selective reduction of portal vein pressure in bile duct-ligated rodents. (2012)
  • 著者名/発表者名: Kageyama, Y., Ikeda, H., Watanabe, N., Nagamine, M., Kusumoto, Y., Yashiro, M., Satoh, Y., Shimosawa, T., Shinozaki, K., Tomiya, T., Inoue, Y., Nishikawa, T., Ohtomo, N., Tanoue, Y., Yokota, H., Koyama, T., Ishimaru, K., Okamoto, Y., Takuwa, Y., Koike, K., and Yatomi
  • 雑誌名: Hepatology 巻: 56 ページ: 1427-1438
• [雑誌論文] Serum autotaxin is not a useful biomarker for ovarian cancer. (2012)
  • 著者名/発表者名: Nakamura, K., Igarashi, K., Ohkawa, R., Yokota, H., Masuda, A., Nakagawa, S., Yano, T., Ikeda, H., Aoki, J., and Yatomi, Y.
  • 雑誌名: Lipids 巻: 47 ページ: 927-930
• [雑誌論文] FTY720 improves functional recovery after spinal cord injury by primarily nonimmunomodulatory mechanisms. (2012)
  • 著者名/発表者名: Norimatsu, Y., Ohmori, T., Kimura, A., Madoiwa, S., Mimuro, J., Seichi, A., Yatomi, Y., Hoshino, Y., and Sakata, Y.
  • 雑誌名: Am. J. Pathol 巻: 180 ページ: 1625-1635
• [雑誌論文] Development of an enzymatic assay for sphingomyelin with rapid and automatable performances: Analysis in healthy subjects and coronary heart disease patients. (2012)
  • 著者名/発表者名: Ohkawa, R., Kishimoto, T., Kurano, M., Dohi, T., Miyauchi, K., Daida, H., Nagasaki, M., Uno, K., Hayashi, N., Sakai, N., Matsuyama, N., Nojiri, T., Nakamura, K., Okubo, S., Yokota, H., Ikeda, H., and Yatomi, Y.
  • 雑誌名: Clin. Biochem. 巻: 45 ページ: 1463-1470
• [雑誌論文] H. Increased activity of serum mitochondrial isoenzyme of creatine kinase in hepatocellular carcinoma patients predominantly with recurrence. (2012)
  • 著者名/発表者名: Soroida, Y., Ohkawa, R., Nakagawa, H., Satoh, Y., Yoshida, H., Kinoshita, H., Tateishi, R., Masuzaki, R., Enooku, K., Shiina, S., Sato, T., Obi, S., Hoshino, T., Nagatomo, R., Okubo, S., Yokota, H., Koike, K., Yatomi, Y., and Ikeda
  • 雑誌名: J. Hepatology 巻: 57 ページ: 330-336
• [雑誌論文] Analytical evaluation of plasma serotonin and sphingosine 1-phosphate and their clinical assessment in early atherosclerosis. (2012)
  • 著者名/発表者名: Sugiura, T., Dohi, Y., Yamashita, S., Ohte, N., Ito, S., Iwaki, S., Hirowatari, Y., Ohkawa, R., Mishima, Y., Yatomi, Y., Kimura, G., and Fujii, S.
  • 雑誌名: Coron. Artery Dis., 2012 巻: 23 ページ: 234-238
• [雑誌論文] Autotaxin in liver fibrosis. (2012)
  • 著者名/発表者名: Ikeda, H. and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 413 ページ: 1817-1821
• [雑誌論文] Decreased circulating lipoprotein-associated phospholipase A2 levels are associated with coronary plaque regression in patients with acute coronary syndrome. (2011)
  • 著者名/発表者名: Dohi, T., Miyauchi, K., Okazaki, S., Yokoyama, T., Ohkawa, R., Nakamura, K., Yanagisawa, N., Tsuboi, S., Ogita, M., Yokoyama, K., Kurata, T., Yatomi, Y., and Daida, H.
  • 雑誌名: Atherosclerosis 巻: 219 ページ: 907-912
• [雑誌論文] Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C. (2011)
  • 著者名/発表者名: Ikeda, H., Tateishi, R., Enooku, K., Yoshida, H., Nakagawa, H., Masuzaki, R., Kondo, Y., Goto, T., Shiina, S., Kume, Y., Tomiya, T., Inoue, Y., Nishikawa, T., Ohtomo, N., Tanoue, Y., Ono, T., Koike, K., and Yatomi, Y.
  • 雑誌名: Cancer Epidemiol. Biomarkers Prev 巻: 20 ページ: 2204-2211
• [雑誌論文] Serum autotaxin measurements in pregnant women: application for the differentiation of normal pregnancy and pregnancy-induced hypertension. (2011)
  • 著者名/発表者名: Masuda, A., Fujii, T., Iwasawa, Y., Nakamura, K., Ohkawa, R., Igarashi, K., Okudaira, S., Ikeda, H., Kozuma, S., Aoki, J., and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 412 ページ: 1944-1950
• [雑誌論文] Autotaxin as a novel serum marker of liver fibrosis. (2011)
  • 著者名/発表者名: Nakagawa, H., Ikeda, H., Nakamura, K., Ohkawa, R., Masuzaki, R., Tateishi, R., Yoshida, H., Watanabe, N., Tejima, K., Kume, Y., Iwai, T., Suzuki, A., Tomiya, T., Inoue, Y., Nishikawa, T., Ohtomo, N., Tanoue, Y., Omata, M., Igarashi, K., Aoki, J., Koike, K., and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 412 ページ: 1201-1206
• [雑誌論文] Specific increase in serum autotaxin activity in patients with pancreatic cancer. (2011)
  • 著者名/発表者名: Nakai, Y., Ikeda, H., Nakamura, K., Kume, Y., Fujishiro, M., Sasahira, N., Hirano, K., Isayama, H., Tada, M., Kawabe, T., Komatsu, Y., Omata, M., Aoki, J., Koike, K., and Yatomi, Y.
  • 雑誌名: Clin. Biochem. 巻: 44 ページ: 576-581
• [雑誌論文] Plasma concentration of bioactive lipid mediator sphingosine 1-phosphate is reduced in patients with chronic hepatitis C. (2010)
  • 著者名/発表者名: Ikeda, H., Ohkawa, R., Watanabe, N., Nakamura, K., Kume, Y., Nakagawa, H., Yoshida, H., Okubo, S., Yokota, H., Tomiya, T., Inoue, Y., Nishikawa, T., Ohtomo, N., Tanoue, Y., Koike, K., and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 411 ページ: 765-770
• [雑誌論文] Unbalanced expression of sphingosine1-phosphate receptors in diabetic nephropathy. (2010)
  • 著者名/発表者名: Imasawa, T., Kitamura, H., Ohkawa, R., Satoh, Y., Miyashita, A., and Yatomi, Y.
  • 雑誌名: Exp. Toxicol. Pathol. 巻: 62 ページ: 53-60
• [雑誌論文] Blockade of sphingosine 1-phosphate receptor 2 signaling attenuates streptozotocin-induced apoptosis ofpancreatic beta-cells. Biochem. (2010)
  • 著者名/発表者名: Imasawa, T., Koike, K., Ishii, I., Chun, J., and Yatomi, Y.
  • 雑誌名: Biophys. Res. Commun 巻: 392 ページ: 207-211
• [雑誌論文] A novel enzyme immunoassay for the determination of phosphatidylserine-specific phospholipase A(1) in human serum samples. (2010)
  • 著者名/発表者名: Nakamura, K., Igarashi, K., Ohkawa, R., Saiki, N., Nagasaki, M., Uno, K., Hayashi, N., Sawada, T., Syukuya, K., Yokota, H., Arai, H., Ikeda, H., Aoki, J., and Yatomi, Y.
  • 雑誌名: Clin. Chim. Acta 巻: 411 ページ: 1090-1094
• [雑誌論文] Liquid chromatography/mass spectrometry analysis revealing preferential occurrence of non-arachidonate-containing phosphatidylinositol bisphosphate species in nuclei and changes in their levels during cell cycle. (2010)
  • 著者名/発表者名: Ogiso, H., Nakamura, K., Yatomi, Y., Shimizu, T., and Taguchi, R.
  • 雑誌名: Rapid Commun. Mass Spectrom 巻: 24 ページ: 436-442
• [雑誌論文] Sustained delivery of sphingosine-1-phosphate using poly(lactic-co-glycolic acid)-based microparticles stimulates Akt/ERK-eNOS mediated angiogenesis and vascular maturation restoring blood flow in ischemic limbs of mice. (2010)
  • 著者名/発表者名: Qi, X., Okamoto, Y., Murakawa, T., Wang, F., Oyama, O., Ohkawa, R., Yoshioka, K., Du, W., Sugimoto, N., Yatomi, Y., Takuwa, N., and Takuwa, Y.
  • 雑誌名: Eur. J. Pharmacol. 巻: 634 ページ: 121-131
• [雑誌論文] Increased circulating plasma lysophosphatidic acid in patients with acute coronary syndrome. (2010)
  • 著者名/発表者名: Dohi, T., Miyauchi, K., Ohkawa, R., Nakamura, K., Kishimoto, T., Miyazaki, T., Nishino, A., Nakajima, N., Yaginuma, K., Tamura, H., Kojima, T., Yokoyama, K., Kurata, T., Shimada, K., Yatomi, Y., and Daida, H.
  • 雑誌名: Clin. Chim. Acta 巻: 413 ページ: 207-212
• [雑誌論文] Liver involvement in sphingosine 1-phosphate dynamism revealed by adenoviral hepatic overexpression of apolipoprotein M.
  • 著者名/発表者名: Kurano, M., Tsukamoto, K., Ohkawa, R., Hara, M., Iino, J., Kageyama, Y., Ikeda, H., and Yatomi, Y.
  • 雑誌名: Atherosclerosis, in press.
• [雑誌論文] Increased lysophosphatidic acid levels in culprit coronary arteries of patients withacute coronary syndrome.
  • 著者名/発表者名: Dohi, T., Miyauchi, K., Ohkawa, R., Nakamura, K., Kurano, M., Kishimoto, T., Yanagisawa, N., Ogita, M., Miyazaki, T., Nishino, A., Yaginuma, K., Tamura, H., Kojima, T., Yokoyama, K., Kurata, T., Shimada, K., Daida, H., and Yatomi, Y.
  • 雑誌名: Atherosclerosis, in press.
• [雑誌論文] Lysophosphatidic acid receptor LPA is essential for development of arthritis.
  • 著者名/発表者名: Miyabe, Y., Miyabe, C., Iwai, Y., Takayasu, A., Fukuda, S., Yokoyama, W., Nagai, J., Jona, M., Tokuhara, Y., Ohkawa, R., Albers, H.M., Ovaa, H., Aoki, J., Chun, J., Yatomi, Y., Ueda, H., Miyasaka, M., Miyasaka, N., and Nanki, T.
  • 雑誌名: Arthritis Rheum 巻: (in press)
• [雑誌論文] Inhibition of Lysophosphatidic Acid (LPA) Increase by Pre-storage Whole-Blood Leukocyte Reduction in Autologous CPDA-1 Whole Blood.
  • 著者名/発表者名: Nagura, Y., Tsuno, N.H., Ohkawa, R., Nojiri, T., Tokuhara, Y., Matsuhashi, M., Yatomi, Y., and Takahashi, K.
  • 雑誌名: Transfusion, in press.
• [学会発表] Serum phosphatidylserine-specific phospholipase A1 (PS-PLA1) identified as a novel biomarker for systemic lupus erythematosus (SLE). (2012)
  • 著者名/発表者名: Sawada, T., Nakamura, K., Ohkawa, R., Shoji, A., Tahara, K., Hayashi, H., Kimura, E., Igarashi, K., Aoki, J., and Yatomi, Y.
  • 学会等名: American College of Rheumatology 76th Annual Meeting
  • 発表場所: Washington DC, USA.
  • 年月日: 20121109-0914
• [学会発表] Hepatic Apolipoprotein M Overexpression Increased Total Sphingosine 1-phosphate Mass and Ameliorate Insulin Resistance in Diet Induced Obesity Mice. (2012)
  • 著者名/発表者名: Kurano, M., Tsukamoto, K., Ohkawa, R., Hara, M., Iino, J., Ikeda, H., and Yatomi, Y.
  • 学会等名: Scientific Session of the American Heart Association.
  • 発表場所: CA, USA.
  • 年月日: 20121103-1107
• [学会発表] Possible Usefulness of the Assay of Choline and Choline-containing Phospholipids in Clinical Laboratory Medicine in the Fields of Dyslipidemia and Atherosclerosis. Scientific Session of the American Heart Association. (2012)
  • 著者名/発表者名: Ohkawa, R., Kishimoto, T., Kurano, M., Dohi, T., Miyauchi, K., Daida, H., Nagasaki, M., Uno, K., Hayashi, N., Sakai, N., Matsuyama, N., Nojiri, T., Nakamura, K., Okubo, S., Yokota, H., Ikeda, H., and Yatomi, Y.
  • 学会等名: AHA Scientific Sessions
  • 発表場所: CA, USA.
  • 年月日: 20121103-1107
• [学会発表] Metabolism of lysophospholipids in the blood. (2011)
  • 著者名/発表者名: Yatomi, Y.
  • 学会等名: XXIIIrd Congress of the International Society on Thrombosis and Haemostasis.
  • 発表場所: Kyoto Japan.
  • 年月日: 20110723-0728
• [学会発表] their related molecules: its introduction into clinical laboratory medicine. (2010)
  • 著者名/発表者名: Yatomi, Y., Igarashi, K., Nakamura, K., Ohkawa, R., Masuda, A., Ikeda, H., and Aoki, J. Analysis of lysophospholipids and
  • 学会等名: The 27th Naito Conference on "Membrane Dynamics and Lipid Biology[I]".
  • 発表場所: Sapporo, Hokkaido, Japan
  • 年月日: 20100629-0702
• [学会発表] Clinical introduction of plasma lysophosphatidic acid and serum autotaxin assays. Keystone Symposia: Bioactive Lipids (2010)
  • 著者名/発表者名: Yatomi, Y.
  • 学会等名: Biochemistry and Diseases.
  • 発表場所: Kyoto, Japan.
  • 年月日: 20100606-0611
• [学会発表] Usefulness of the enzyme immunoassay of serum autotaxin reflecting the plasma lysophosphatidic acid level. (2010)
  • 著者名/発表者名: Yatomi, Y., Igarashi, K., Nakamura, K., Ohkawa, R., Masuda, A., Ikeda, H., and Aoki, J.
  • 学会等名: Keystone Symposia: Bioactive Lipids: Biochemistry and Diseases.
  • 発表場所: Kyoto, Japan.
  • 年月日: 20100606-0611
• [学会発表] Lipid mediators and atherothrombosis. (2010)
  • 著者名/発表者名: Yatomi, Y.
  • 学会等名: XXth World Congress of the International Society for Heart Research.
  • 発表場所: Kyoto, Japan.
  • 年月日: 20100513-0516
• [学会発表] Clinical laboratory medicine of lysophospholipid mediators. (2010)
  • 著者名/発表者名: Yatomi, Y.
  • 学会等名: The 7th Seoul National University College of Medicine ?The University of Tokyo Faculty of Medicine Joint Conference.
  • 発表場所: Seoul, Korea
  • 年月日: 2010-05-28
• [図書] Clinical Introduction of Lysophosphatidic Acid and Autotaxin Assays.
  • 著者名/発表者名: Yatomi, Y. Igarashi, K., Nakamura, K., Ohkawa, R., Masuda, A., Suzuki, A., Kishimoto, T., Ikeda, H., and Aoki, J.
  • 出版者: Lysophospholipid Receptors: Signaling and Biochemistry (ed., J. Chun) John Wiley, USA., in press.
• [産業財産権] ホスファチジルセリン特異的ホスホリ パーゼA1測定による (2012)
  • 発明者名: 矢冨裕,中村和宏,五十嵐浩二,青 木淳賢,沢田哲治
  • 権利者名: 矢冨裕,中村和宏,五十嵐浩二,青 木淳賢,沢田哲治
  • 産業財産権番号: 特許 2012-032278
  • 取得年月日: 2012-02-16
  • 外国
• [産業財産権] オートタキシン測定による肝線維化の 検査方法および検査薬 (2011)
  • 発明者名: 矢冨裕,中村和宏,池田均,五十嵐 浩二
  • 権利者名: 矢冨裕,中村和宏,池田均,五十嵐 浩二
  • 産業財産権番号: 特許 WO2011/081214
  • 取得年月日: 2011-07-07
• [産業財産権] オートタキシン測定による膵疾患の検 査方法および検査薬 (2010)
  • 発明者名: 矢冨裕,池田均,中井陽介,中村和 宏,五十嵐浩二
  • 権利者名: 矢冨裕,池田均,中井陽介,中村和 宏,五十嵐浩二
  • 産業財産権番号: 特許 特願 2010-194658
  • 出願年月日: 2010-08-31
  • 外国