内科学講座 【末盛6階】
研究
 
 
 
研究内容
 私たちは、循環器分野、糖尿病分野を中心として、心血管病や糖尿病合併症の発症・進展メカニズムの解明を目指して研究を進めています。また、歯学部内科の特徴を生かして、歯科疾患と全身疾患の関連についても積極的に研究しています。さらに、前駆細胞や幹細胞の特性の探索やこれらを用いた再生医療にも取り組んでいます。
1.歯周炎が動脈硬化初期病変を誘導 ―動脈硬化予防における歯周病治療の重要性を示唆―
図1
図1. 歯周炎の惹起は、大動脈血管内皮細胞におけるNF-kB/VCAM-1発現を増強する
図2
図2. 歯周病による動脈硬化初期病変誘導の機序
 近年慢性炎症である歯周炎が動脈硬化の進展に関与する可能性が、疫学研究や動物実験により報告されています。しかし、歯周炎が動脈硬化の進展に関与する機序については、未だ一定の見解が得られていません。私たちは、ラットに実験的歯周炎を惹起して検討を行った結果、歯周炎により活性化した単球/マクロファージが大動脈に接着し作用を及ぼすことにより、大動脈におけるTNF-α遺伝子発現、その経路であるTNFR1/TRAF2/RIPおよび接着分子であるVCAM-1発現が増加し、大動脈内膜への単球接着を亢進させることを明らかにしました(Sci Rep 4:5171, 2014)。実際に大動脈内膜を免疫染色して観察すると、血管内皮細胞の細胞核周囲にNF-κBの発現増強とともにVCAM-1が発現していることが確認できました(図1)。こうした事実は、歯周炎が動脈硬化に関与する新たな経路を示す(図2)とともに、動脈硬化の初期病変において歯周炎が重要な役割を担っている可能性を示唆しています。なお、この成果は新聞各紙(中日、毎日、日本経済)にも取り上げられました。。
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2.前駆細胞/幹細胞と再生医療 ―機能解明と細胞移植療法―
 幹細胞は組織や臓器に成長する元となる細胞であり、特定の細胞にだけ分化する能力を持つ「体性幹細胞」と、体を作るあらゆる細胞に分化できる「多能性幹細胞」に大別できます。万能細胞と呼ばれるすべての細胞に分化可能な細胞が多能性幹細胞であり、ES細胞、iPS細胞がそれにあたります。そこから分化し、ある決まった種類の細胞に分化する方向性を持った細胞が造血幹細胞、神経幹細胞、間葉系幹細胞、歯髄幹細胞などの体性幹細胞であり、幹細胞よりさらに特定の細胞に向けて分化した細胞が血管内皮前駆細胞などの前駆細胞です。体性幹細胞や前駆細胞は、成人では骨髄や臍帯血中に最も多く存在しますが、組織中にも存在し、組織の修復や再生に寄与しています。
 血管内皮前駆細胞は、血管の修復や血管形成に関わる重要な細胞です(図3)。私たちは、血管内皮前駆細胞を高グルコース状態に曝露すると、細胞増殖が障害され、アポトーシスを増加させること、糖尿病患者では血管内皮前駆細胞数が低下しており、糖尿病患者において血管内皮前駆細胞数はHbA1c と負に相関することを見出しました (J Diabetes Invest 2: 262-270, 2011)。 
 間葉系幹細胞の一種である歯髄幹細胞は、乳歯や矯正を目的に抜去した歯の歯髄より採取できること、培養増殖が比較的容易で、凍結保存後もその細胞機能を維持していることより、再生医療の細胞ソースとして期待されています。歯髄は咀嚼などにより常にメカニカルストレスを受けています。私たちは、メカニカルストレスが歯髄幹細胞の骨や象牙質への分化を抑制しながら細胞増殖を促進させることを解明しました(Tissue Eng Part A 19: 625-633, 2013)。すなわち、メカニカルストレスが、歯髄幹細胞を未分化のまま維持することに役立っていると考えられます。
 さらに前駆細胞や幹細胞を用いた再生医療にも取り組んでいます。糖尿病性神経障害は、糖尿病合併症の中で最も頻度の高い合併症です。現在の治療は、自覚症状に対する対症療法が中心ですが、より根本的な治療法として、私たちは骨髄単核球、血管内皮前駆細胞、または間葉系幹細胞などを用いた細胞移植療法が有効であることを、動物実験を用いて示しました(PLoS One 6:e27458, 2011)。
図3
図3. 血管内皮前駆細胞の機能
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3.糖尿病における歯周病進展機序の解明
     ―糖尿病における歯周病の増悪には、ニトロ化ストレスが関与―
図4.
図4. 糖尿病における歯周病増悪とニトロ化ストレスの関係
 歯周病は歯周ポケット内に存在する細菌などの感染によって歯周組織が破壊される炎症性疾患です。炎症の進行により歯槽骨が吸収され、症状が重篤化すると歯は動揺し、支持を失った歯は脱落します。糖尿病患者における歯周病は、高い罹患率と重症化を特徴とし、歯周病は糖尿病合併症の一つとされています。糖尿病における免疫機能の低下や代謝障害、血流障害などが原因と考えられていますが、その機序はいまだ明確ではありません。       
 私たちは、糖尿病ラットに実験的歯周炎を惹起させ、その機序を検討しました。糖尿病ラットでは、正常ラットと比較し、歯周炎惹起により著明な炎症性細胞浸潤と歯槽骨の吸収が起こります。糖尿病では歯周炎により歯周組織に炎症性サイトカインであるTNF-αおよびiNOSが過剰発現していました。iNOSを介して発生するNOは高い反応性のフリーラジカルであり、過剰なNOはパーオキシナイトライトを産生し、ニトロ化反応により直接細胞を障害することが知られています。これまでの研究により、糖尿病ラットの歯周炎ではニトロ化ストレスのマーカーであるニトロチロシンが増加していることがわかりました(図4)(J Clin Periodontol 39:342-349, 2012)。現在、ニトロ化ストレスの抑制が、糖尿病における歯周病の改善に寄与するかどうかを検討しています。
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4.糖尿病と歯周病 ―双方向性に関する臨床研究―
図5
図5. 糖尿病と歯周病ー双方向性関係ー
 糖尿病患者の血糖コントロール悪化が合併する歯周病を増悪させるといわれています。一方、歯周病が重症であるほど血糖コントロールが不良となり、歯周病治療により炎症が抑えられると血糖が改善することが報告されています。
 私たちは口腔衛生学講座、歯周病学講座と共同研究を行い、疫学調査により糖尿病と歯周病が互いに関わりを持つことを証明しました(図5)(J Dent Res 91:161-166, 2012)。また、他大学とも連携し、糖尿病治療により血糖コントロールが改善すれば歯周病の状態も良化することを報告しました(J Diabetes Invest 4:320-325, 2013)。
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5.メタボリックシンドローム患者の治療 ―スタチンの有用性―
図6
図6. 血中アディポネクチンに及ぼすスタチンの効果
 心筋梗塞や脳卒中の原因となる動脈硬化は、多くの因子が絡まり合って進行します。代表的な因子は、高血圧、脂質異常症、糖尿病ですが、これらは互いに合併する頻度の高いことが知られており、肥満(内臓脂肪蓄積)を共通の発症基盤とするメタボリックシンドロームという概念が提唱されました。
 私たちは他の病院と共同して臨床研究を実施し、メタボリックシンドローム患者に対するスタチン(動脈硬化を促進するLDLコレステロールを減少させる薬剤)の有効性を検討しました。メタボリックシンドローム患者では抗動脈硬化作用を持つ血液中のアディポネクチンが低下しており、スタチンにより善玉のHDLコレステロールが増加する症例ではアディポネクチンも増えており、動脈硬化の抑制に寄与することが示唆されました(図6)(J Cardiol 60:389-394, 2012)。
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6.生活習慣病の遺伝子リスク解析 ―地域住民を対象とした疫学調査―
 生活習慣病には、環境因子と遺伝因子が関与していることが明らかになってきています。私たちは他施設との共同研究により、地域住民の協力を得て、生活習慣病の感受性遺伝子の解析に努めてきました。こういった遺伝子の解明は、当該疾患の予知・予防に極めて重要であり、将来的にはオーダーメイド医療も可能となってきます。私たちは、その成果の一環として、心筋梗塞発症に関わる感受性遺伝子を発見しました(図7)(Circ Cardiovasc Genet 6:569-578, 2013)。
 また、エピゲノムワイド関連解析を用いた研究も進めており、国内・外の研究機関との共同研究により、高血圧に関連する遺伝子座を同定し、DNAメチル化との関係も明らかにしました(Nat Genet 47:1282-1293, 2015)。さらに、インスリン抵抗性と関連があると考えられているレジスチンの一塩基多型が近隣のDNAメチル化を介し血中レジスチン濃度を調節している可能性を報告しました(Diabetologia 58:2781-2790, 2015)。今後も、生活習慣病の遺伝子リスク解析を実施し、研究を展開していく予定です。
図7
図7. ALMS1は心筋梗塞感受性遺伝子である
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研究業績(2010年〜)
2016年
1. Omi M, Hata M, Nakamura N, Miyabe M, Kobayashi Y, Kamiya H, Nakamura J, Ozawa S, Tanaka Y, Takebe J, Matsubara T, Naruse K: Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy. Journal of Diabetes Investigation 7:485-496, 2016.
2. Suzuki Y, Nakamura N, Miyabe M, Nishikawa T, Miyajima S, Adachi K, Mizutani M, Kikuchi T, Miyazawa K, Goto S, Tsukiyama K, Yamada Y, Ohno N, Noguchi H, Mitani A, Matsubara T, Naruse K: Anti-inflammatory role of glucose-dependent insulinotropic polypeptide in periodontitis. Journal of Diabetes Investigation 7:497-505, 2016.
3. Umemoto N, Ishii H, Kamoi D, Aoyama T, Sakakibara T, Takahashi H, Tanaka A, Yasuda Y, Suzuki S, Matsubara T, Murohara T: Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis. Atherosclerosis 249:65-69, 2016.
4. Harada K, Shibata R, Ouchi N, Tokuda Y, Funakubo H, Suzuki M, Kataoka T, Nagao T, Okumura S, Shinoda N, Kato B, Sakai S, Kato M, Ishii H, Amano T, Matsubara T, Murohara T: Increased expression of the adipocytokine omentin in the epicardial adipose tissue of coronary artery disease patients. Atherosclerosis 251:299-304, 2016.
5. Oguri M, Ishii H, Yasuda K, Kawanishi H, Hanaki Y, Kamiya H, Matsubara T, Murohara T: Clinical characteristics of patients hospitalized for acute heart failure according to hospital arrival timing. Journal of Cardiology 68:379-383, 2016.
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2015年
6. Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Leach IM, Drong AW, Abbott J, Wahl S, Tan S-T, Scott WR, Campanella G, Chadeau-Hyam M, Afzal U, Ahluwalia TS, Bonder MJ, Chen P, Dehghan A, Edwards TL, Esko T, Go MJ, Harris SE, Hartiala J, Kasela S, Kasturiratne A, Khor C-C, Kleber ME, Li H, Mok ZY, Nakatochi M, Sapari NS, Saxena R, Stewart AFR, Stolk L, Tabara Y, Matsubara T, et al: Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nature Genetics 47:1282-1293, 2015.
7. Nakatochi M, Ichihara S, Yamamoto K, Ohnaka K, Kato Y, Yokota S, Hirashiki A, Naruse K, Asano H, Izawa H, Matsubara T, Yokota M: Epigenome-wide association study suggests that SNPs in the promotor region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites. Diabetologia 58:2781-2790, 2015.
8. Hata M, Omi M, Kobayashi Y, Nakamura N, Tosaki T, Miyabe M, Kojima N, Kubo K, Ozawa S, Maeda H, Tanaka Y, Matsubara T, Naruse K: Transplantation of cultured dental pulp stem cells into the skeletal muscles ameliorated diabetic polyneuropathy: therapeutic plausibility of freshly isolated and cryopreserved dental pulp stem cells. Stem Cell Research and Therapy 6:162, 2015.
9. Tsuda T, Ishii H, Ichimiya S, Kanashiro M, Watanabe J, Takefuji M, Aoyama T, Suzuki S, Tanaka A, Matsubara T, Murohara T: Assessment of in-stent restenosis using high-definition computed tomography with a new gemstone detector. Circulation Journal 79:1542-1548, 2015.
10. Kumagai S, Amano T, Takashima H, Waseda K, Kurita A, Ando H, Maeda K, Ito Y, Ishii I, Hayashi M, Yoshikawa D, Suzuki S, Tanaka A, Matsubara T, Murohara T: Impact of cigarette smoking on coronary plaque composition. Coronary Artery Disease 26:60-65, 2015.
11. Uchida Y, Ichimiya S, Ishii H, Kanashiro M, Watanabe J, Hayano S, Suzuki S, Takeshita K, Sakai S, Amano T, Matsubara T, Murohara T: Impact of admission anemia on coronary microcirculation and clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. International Heart Journal 56:381-388, 2015.
12. Himeno T, Kamiya H, Naruse K, Zhao Cheng, Ito S, Shibata T, Kondo M, Kato J, Okawa T, Fujiya A, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K, Nakamura J: Angioblast derived from ES cells construct blood vessels and ameliorate diabetic polyneuropathy in mice. Journal of Diabetes Research 2015:257230, 2015.
13. Kondo M, Kamiya H, Himeno T, Naruse K, Nakashima E, Watarai A, Shibata T, Tosaki T, Kato J, Okawa T, Hamada Y, Isobe K, Oiso Y, Nakamura J: Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes. Journal of Diabetes Investigation 6:140-149, 2015.
14. Hayakawa S, Ohashi K, Shibata R, Kataoka Y, Miyabe M, Enomoto T, Joki Y, Shimizu Y, Kambara T, Uemura Y, Yuasa D, Ogawa H, Matsuo K, Hiramatsu-Ito M, van den Hoff MJ, Walsh K, Murohara T, Ouchi N: Cardiac myocyte-derived follistatin-like 1 prevents renal injury in a subtotal nephrectomy model. Journal of American Society of Nephrology 26:636-646, 2015.
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2014年
15. Ito Y, Mizuno M, Suzuki Y, Tamai H, Hiramatsu T, Ohashi H, Ito I, Kasuga H, Horie M, Maruyama S, Yuzawa Y, Matsubara T, Matsuo S: Long-term effects of spironolactone in peritoneal dialysis patients. Journal of American Society of Nephrology 25: 1094-1102, 2014.
16. Soboku K, Kikuchi T, Fujita S, Takeda H, Naruse K, Matsubara T, Noguchi T: Altered gene expression in gingival tissues and enhanced bone loss in rats with diabetes with experimental periodontitis. Journal of Periodontology 85:454-464, 2014.
17. Miyajima S, Naruse K, Kobayashi Y, Nakamura N, Nishikawa T, Adachi K, Suzuki Y, Kikuchi T, Mitani A, Mizutani M, Ohno T, Noguchi T, Matsubara T: Periodontitis-activated monocytes/macrophages cause aortic inflammation. Scientific Reports 4:5171, 2014.
18. Kumagai S, Ishii H, Takashima H, Waseda K, Kurita A, Ando H, Gosho M, Yoshikawa D, Suzuki S, Tanaka A, Matsubara T, Murohara T, Amano T: Impact of chronic obstructive pulmonary disease on composition of left main coronary artery plaque with intermediate stenosis. International Journal of Cardiology 174:865-866, 2014.
19. Harada K, Harada K, Uetani T, Kataoka T, Takeshita M, Kunimura A, Takeyama Y, Shinoda N, Kato B, Kato M, Marui N, Ishii I, Matsubara T, Amano T, Murohara T: The different association of epicardial fat with coronary plaque in patients with acute coronary syndrome and patients with stable angina pectoris: Analysis using integrated backscatter intravascular ultrasound. Atherosclerosis 236:301-306, 2014.
20. Harada K, Amano T, Kataoka T, Takeshita M, Harada K, Kunimura A, Takayama Y, Shinoda N, Kato B, Uetani T, Kato M, Marui N, Ishii H, Matsubara T, Murohara T: Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients. Atherosclerosis 237:671-676, 2014.
21. Kumagai S, Takashima H, Waseda K, Ando H, Suzuki A, Uetani H, Harada K, Yoshida T, Kunimura A, Shimbo Y, Kitagawa K, Harada K, Ishii H, Yoshikawa D, Matsubara T, Murohara T, Amano T: Prognostic impact of lipid contents on the target lesion in patients with drug eluting stent implantation. Heart and Vessels 29:761-768, 2014.
22. Naruse K: Diabetes and periodontal disease: What should we learn next? Journal of Diabetes Investigation 5: 249-250, 2014.
23. Kato J, Kamiya H, Himeno T, Shibata T, Kondo M, Okawa T, Fujiya A, Fukami A, Uenishi E, Seino Y, Tsunekawa S, Hamada Y, Naruse K, Oiso Y, Nakamura J: Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats. Journal of Diabetes and its Complications 28: 588-595, 2014.
24. Miyabe M, Ohashi K, Shibata R, Uemura Y, Ogura Y, Yuasa D, Kambara T, Kataoka Y, Yamamoto T, Matsuo K, Enomoto T, Hayakawa S, Hiramatsu-Ito M, Ito M, Van Den HoffMJ, Walsh K, Murohara T, Ouchi N: Muscle-derived follistatin-like 1 function to reduce neointimal formation after vascular injury. Cardiovascular Research, 103:111-120 2014.
25. Yuasa D, Ohashi K, Shibata R, Takeshita K, Kikuchi R, Takahashi R, Kataoka Y, Miyabe M, Joki Y, Kambara T, Uemura Y, Matsuo K, Hayakawa S, Hiramatsu-Ito M, Ito M, Ikeda N, Murohara T, Ouchi N: Association of circulating C1q/TNF -related protein 1 levels with coronary artery disease in men. PLoS One 9:e99846, 2014.
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2013年
26. Hata M, Naruse K, Ozawa S, Kobayashi Y, Nakamura N, Kojima N, Omi M, Katanosaka Y, Nishikawa T, Naruse K, Tanaka Y, Matsubara T: Mechanical stretch increases the proliferation while inhibiting the osteogenic differentiation in dental pulp stem cells. Tissue Engineering: Part A 19: 625-633, 2013.
27. Kunimura A, Amano T, Uetani T, Harada K, Yoshida T, Suzuki A, Shimbo Y, Kitagawa K, Harada K, Kato B, Kato M, Takashima H, Ando H, Matsubara T, Ishii H, Murohara T: Prognostic impact of concurrence of metabolic syndrome and chronic kidney disease in patients undergoing coronary intervention: Involvement of coronary plaque composition. Journal of Cardiology 61:189-195, 2013.
28. Lee JY, Lee BS, Shin DJ, Park KW, Shin YA, Kim KJ, Heo L, Lee JY, Kim YK, Kim YJ, Hong CB, Lee SH, Yoon D, Ku HJ, Oh IY, Kim BJ, Lee J, Park SJ, Kim J, Kawk H, Lee JE, Park H, Lee JE, Nam H, Park H, Shin C, Yokota M, Asano H, Nakatochi M, Matsubara T, Kitajima H, Yamamoto K, Kim HL, Han BG, Cho MC, Jang Y, Kim HS, Park JE, Lee JY: A genome-wide association study of a coronary artery disease risk variant. Journal of Human Genetics 58:120-126, 2013.
29. Sato B, Yoshikawa D, Ishii H, Kikuchi R, Arima T, Takeshita K, Inoue Y, Suzuki S, Tanaka M, Kumagai S, Matsumoto M, Hayashi H, Ando H, Amano T, Matsubara T, Niwa T, Murohara T: Indoxyl sulfate, a uremic toxin, and carotid intima-media thickness in patients with coronary artery disease. International Journal of Cardiology 163:214-216, 2013.
30. Inoue Y, Yoshikawa D, Ishii H, Isobe S, Kumagai S, Suzuki S, Okumura S, Hayashi M, Matsubara T, Ohshima S, Banno H, Komori K, Kato K, Murohara T: Post-stress perfusion abnormalities detected on myocardial perfusion single-photon emission computed tomography predict long-term mortality after elective abnormal aortic aneurysm repair. Circulation Journal 77: 1229-1234, 2013.
31. Katagiri S, Nitta H, Nagasawa T, Izumi Y, Kanazawa M, Matsuo A, Chiba H, Fukui M, Nakamura N, Oseko F, Kanamura N, Inagaki K, Noguchi T, Naruse K, Matsubara T, Miyazaki S, Miyauchi T, Ando Y, Hanada N, Inoue S: Effect of glycemic control on periodontitis in type 2 diabetic patients with periodontal disease. Journal of Diabetes Investigation 4: 320-325, 2013.
32. Hayano S, Ishii H, Ichimiya S, Kanashiro M, Watanabe J, Suzuki S, Yoshikawa D, Maeda K, Matsubara T, Murohara T: Renal dysfunction and atherosclerosis of the neointima following bare metal stent implantation. American Journal of Nephrology 38: 58-65, 2013.
33. Suzuki S, Ishii H, Matsudaira K, Okumura N, Yoshikawa D, Hayashi M, Maeda K, Kondo T, Kondo T, Ichimiya S, Kato R, Matsubara T, Murohara T: Long-term outcome of drug-eluting vs. bare-metal stents in patients with acute myocardial infarction ― subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS) ―. Circulation Journal 77: 2024-2031, 2013.
34. Ishii H, Aoyama T, Takahashi H, Kamoi D, Tanaka M, Yoshikawa D, Hayashi M, Matsubara T, Murohara T: Serum albumin and C-reactive protein levels predict clinical outcome in hemodialysis patients undergoing endovascular therapy for peripheral artery disease. Atherosclerosis 227: 130-134, 2013.
35. Suzuki S, Ishii H, Ichimiya S, Kanashiro M, Watanabe J, Uchida Y, Yoshikawa D, Maeda K, Matsubara T, Murohara T: Impact of the circadian rhythm on microvascular function in patients with ST-elevation myocardial infarction. International Journal of Cardiology 168:4948-4949, 2013.
36. Ichihara S, Yamamoto K, Asano H, Nakatochi M, Sukegawa M, Ichihara G, Izawa H, Hirashiki A, Takatsu F, Umeda H, Iwase M, Inagaki H, Hirayama H, Sone T, Nishigaki K, Minatoguchi S, Cho M-C, Jang Y, Kim H-S, Park JE, Tada-Oikawa S, Kitajima H, Matsubara T, Sunagawa K, Shimokawa H, Kimura A, Lee J-Y, Murohara T, Inoue I, Yokota M: Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis. Circulation: Cardiovascular Genetics 6: 569-578, 2013.
37. Ando H, Amano T, Takashima H, Harada K, Kitagawa K, Suzuki A, Kunimura A, Shimbo Y, Harada K, Yoshida T, Kato B, Uetani T, Kato M, Matsubara T, Kumagai S, Yoshikawa D, Isobe S, Ishii H, Murohara T: Differences in tissue characterization of restenotic neointima between sirolimus-eluting stent and bare-metal stent: integrated backscatter intravascular ultrasound analysis for in-stent restenosis. European Heart Journal - Cardiovascular Imaging 14:996-1001, 2013.
38. Harada K, Amano T, Uetani T, Yoshida T, Kato B, Marui N, Kumagai S, Ando H, Ishii I, Matsubara T, Murohara T: Association of inflammatory markers with the morphology and extent of coronary plaque as evaluated by 64-slice multidetector computed tomography in patients with stable coronary artery disease. International Journal of Cardiovascular Imaging 29: 1149-1158, 2013.
39. Sato B, Yoshikawa D, Ishii H, Suzuki S, Inoue Y, Takeshita K, Tanaka M, Kumagai S, Matsumoto M, Okumura S, Hayashi H, Matsubara T, Niwa T, Murohara T: Relation of plasma indoxyl sulfate levels and estimated glomerular filtration rate to left ventricular diastolic function. American Journal of Cardiology 111: 712-716, 2013.
40. Kamoi D, Ishii H, Takahashi H, Aoyama T, Toriyama T, Tanaka M, Kawamura Y, Kawashima K, Yoshikawa D, Amano T, Uetani T, Matsubara T, Murohara T: Sirolimus- vs. paclitaxel-eluting stent to coronary intervention in dialysis patients. International Journal of Cardiology 165:533-536, 2013.
41. Okawa T, Kamiya H, Himeno T, Kato J, Seino Y, Fujiya A, Kondo M, Tsunekawa S, Naruse K, Hamada Y, Ozaki N, Cheng Z, Kito T, Suzuki H, Ito S, Oiso Y, Nakamura J, Isobe K. Transplantation of neural crest like cells derived from induced pluripotent stem cells improves diabetic polyneuropathy in mice. Cell Transplantation 22: 1767-1783, 2013.
42. Himeno T, Kamiya H, Naruse K, Cheng Z, Ito S, Kondo M, Okawa T, Fujiya A, Kato J, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K Nakamura J. Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem cells ameliorate diabetic polyneuropathy in mice. BioMed Research International 2013: 259187, 2013.
このページのトップへ
2012年
43. Uchida Y, Ichimiya S, Ishii H, Kanashiro M, Watanabe J, Yoshikawa D, Takeshita K, Sakai S, Amano T, Matsubara T, Murohara T: Impact of plaque burden in the left main coronary artery determined by intravascular ultrasound on cardiovascular events in a Japanese population undergoing percutaneous coronary intervention. American Journal of Cardiology 109: 352-358, 2012.
44. Uemura Y, Watarai M, Ishii H, Koyasu M, Takemoto K, Yoshikawa D, Shibata R, Matsubara T, Murohara T: Atorvastatin 10mg plus ezetimibe 10mg compared with atorvastatin 20mg: Impact on the lipid profile in Japanese patients with abnormal glucose tolerance and coronary artery disease. Journal of Cardiology 59:50-56, 2012.
45. Morita I, Inagaki K, Nakamura F, Noguchi T, Matsubara T, Yoshii S, Nakagaki H, Mizuno K, Sheiham S, Sabbah W: Relationship between periodontal status and levels of glycated hemoglobin. Journal of Dental Research 91:161-166, 2012.
46. Kumagai S, Ishii H, Amano T, Uetani T, Kato B, Harada K, Yoshida T, Ando H, Kunimura A, Shimbo Y, Kitagawa K, Harada K, Hayashi M, Yoshikawa D, Matsubara T, Murohara T: Impact of chronic kidney disease on the incidence of peri-procedural myocardial injury in patients undergoing elective stent implantation. Nephrology Dialysis Transplantation 27:1059-1063, 2012.
47. Nishikawa T, Naruse K, Kobayashi Y, Miyajima S, Mizutani M, Kikuchi T, Soboku K, Nakamura N, Sokabe A, Tosaki T, Hata M, Ohno N, Noguchi T, Matsubara T: Involvement of nitrosative stress in experimental periodontitis in diabetic rats.
Journal of Clinical Periodontology 39:342-349, 2012.
48. Sakakibara T, Ishii H, Toriyama T, Aoyama T, Takahashi H, Kamoi D, Kawamura Y, Kawashima K, Yonada K, Amano T, Tanaka M, Yoshikawa D, Hayashi M, Matsubara T, Murohara T: Sirolimus-eluting stent vs. everolimus- eluting stent for coronary intervention in patients on chronic hemodialysis. Circulation Journal 76:351-355, 2012.
49. Ishii H, Toriyama T, Aoyama T, Takahashi H, Tanaka M, Yoshikawa D, Hayashi M, Yasuda Y, Maruyama S, Matsuo S, Matsubara T, Murohara T: Percutaneous coronary intervention with bare metal stent vs. drug-eluting stent in hemodialysis patients. Circulation Journal 76:1609-1615, 2012.
50. Uchida Y, Ichimiya S, Ishii H, Kanashiro M, Watanabe J, Yoshikawa D, Takeshita K, Sakai S, Amano T, Matsubara T, Murohara T: Impact of metabolic syndrome on various aspects of microcirculation and major adverse cardiac events in patients with ST-segment elevation myocardial infarction. Circulation Journal 76:1972-1979, 2012.
51. Ishii H, Kumada Y, Takahashi H, Toriyama T, Aoyama T, Tanaka M, Yoshikawa D, Hayashi M, Kasuga H, Yasuda Y, Maruyama S, Matsubara T, Matsuo S, Murohara T: Impact of diabetes and glycaemic control on peripheral artery disease in Japanese patients with end-stage renal disease: long-term follow-up study from the beginning of haemodialysis. Diabetologia 55:1304-1309, 2012.
52. Matsubara T, Naruse K, Arakawa T, Nakao M, Yokoi K, Oguri M, Marui N, Amano T, Ichimiya S, Ohashi T, Imai K, Sakai S, Sugiyama S, Ishii H, Murohara T: Impact of high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome. Journal of Cardiology 60:389-394, 2012.
53.Aoyama Y, Hirayama H, Ishii H, Kobayashi K, Ishikawa K, Takigawa M, Nanasato M, Yoshida Y, Aoyama T, Yoshikawa D, Matsubara T, Murohara T: Impact of chronic kidney disease on re-percutaneous coronary intervention for sirolimus-eluting stent restenosis. Coronary Artery Disease 23:528-532, 2012.
54. Uetani T, Amano T, Harada K, Kitagawa K, Kunimura A, Shimbo Y, Harada K, Yoshida T, Kato B, Kato M, Marui N, Nanki M, Hotta N, Ishii H, Matsubara T, Murohara T: Impact of insulin resistance on post-procedural myocardial injury and clinical outcomes in patients who underwent elective coronary interventions with drug-eluting stents. Journal of American College of Cardiology: Cardiovascular Interventions 5:1159-1167, 2012.
55. Kokubo M, Matsubara T, Ueda Y, Murohara T: A giant pseudoaneurysm of the sinus of Valsalva with pulmonary artery obstruction. European Journal of Cardio-Thoracic Surgery 41:1204, 2012.
56. Hayano S, Ichimiya S, Ishii H, Kanashiro M, Watanabe J, Kurebayashi N, Yoshikawa D, Amano T, Matsubara T, Murohara T: Relation between estimated glomerular filtration rate and composition of coronary arterial atherosclerotic plaques. American Journal of Cardiology 109: 1131-1136, 2012.
57. Naruse K. Nerve growth factor: Does this have the potential to become a miraculous treatment for diabetic heart? Journal of Diabetes Investigation 3: 233-234, 2012.
58. Suzuki S, Ichimiya S, Kanashiro M, Watanabe J, Yoshikawa D, Ishii H, Matsubara T, Murohara T: Acute myocardial infarction caused by an anomalous left main coronary artery in a 16-year-old-boy. Journal of Cardiology Cases 5:e55-e57, 2012.
このページのトップへ
2011年
59. Amano T, Matsubara T, Uetani T, Kato M, Kato B, Yoshida T, Harada K, Kumagai S, Kunimura A, Shinbo Y, Ishii H, Murohara T: Lipid-rich plaque predict non-target-lesion ischemic events in patients undergoing percutaneous coronary intervention.― Insights from integrated backscatter intravascular ultrasound ― Circulation Journal, 75: 157-166, 2011.
60. Nakamura N, Naruse K, Kobayashi Y, Matsuki T, Hamada Y, Nakashima E, Kamiya H, Hata M, Nishikawa T, Enomoto A, Takahashi M, Murohara T, Matsubara T, Oiso Y, Nakamura J: High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt. Journal of Diabetes Investigation, 2: 262-270, 2011.
61. Tanimura D, Shibata R, Izawa H, Hirashiki A, Asano H, Murase Y, Miyata S, Nakatochi M, Ouchi N, Ichihara S, Yasui K, Yoshida T, Naruse K, Matsubara T, Yokota M: Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population. European Journal of Human Genetics, 19: 262-269, 2011.
62. Ando H, Amano T, Matsubara T, Uetani T, Nanki M, Marui N, Kato M, Yoshida T, Yokoi K, Kumagai S, Isobe S, Ishii H, Izawa H, Murohara T: Comparison of tissue characteristics between acute coronary syndrome and stable angina pectoris: An integrated backscatter intravascular ultrasound analysis of culprit and non-culprit lesions. Circulation Journal, 75:383-390, 2011.
63. Hamaguchi Y, Tatematsu Y, Furukawa K, Matsubara T, Nakayama S: Imipramine inhibition of TPRM-like plasmalemmal Mg2+ transport in vascular smooth muscle cells. Journal of Cellular and Molecular Medicine, 15:593-601, 2011.
64. Nakatochi M, Miyata S, Tanimura D, Izawa H, Asano H, Murase Y, Kato R, Ichihara S, Naruse K, Matsubara T, Honda H, Yokota M: The ratio of adiponectin to homeostasis model assessment of insulin resistance is a powerful index of each component of metabolic syndrome in an aged Japanese population: Results from KING Study. Diabetes Research and Clinical Practice, 92: e61-e65, 2011.
65. Harada K, Amano T, Uetani T, Funahashi H, Arai K, Okada K, Hirashiki A, Hayashi M, Oshima S, Ishii H, Izawa H, Matsubara T, Murohara T: Accuracy of 64-slice multidetector computed tomography for classification and quantitation of coronary plaque: Comparison with integrated backscatter intravascular ultrasound.International. Journal of Cardiology, 149:95-101, 2011.
66.Takeuchi T, Isobe S, Sato K, Kato MI, Kasai NN, Ohyama H, Yoshikawa D, Ishii H, Matsubara T, Murohara T: Cystatin C: a possible sensitive marker for detecting potential kidney injury after computed tomography coronary angiography. Journal of Computer Assisted Tomography, 35:240-245, 2011.
67. Harada K, Amano T, Uetani T, Tokuda Y, Kitagawa K, Shimbo Y, Kunimura A, Kumagai S, Yoshida T, Kato B, Kato M, Marui N, Ishii H, Matsubara T, Murohara T: Cardiac 64-multislice computed tomography reveals increased epicardial fat volume in patients with acute coronary syndrome. American Journal of Cardiology, 108: 1119-1123, 2011.
68. Amano T, Matsubara T, Uetani T, Kato M, Kato B, Yoshida T, Harada K, Kumagai S, Kunimura A, Shinbo Y, Ishii H, Murohara T: Impact of ω-3 polyunsaturated fatty acids on coronary plaque instability: an integrated backscatter intravascular ultrasound study. Atherosclerosis, 218:110-116, 2011.
69. Naruse K, Sato J, Funakubo M, Hata M, Nakamura N, Kobayashi Y, Kamiya H, Shibata T, Kondo M, Himeno T, Matsubara T, Oiso Y, Nakamura J: Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy. PLoS One 6:e27458, 2011.
70. Suzuki J, Akahane K, Nakamura J, Naruse K, Kamiya H, Himeno T, Nakamura N, Shibata T, Kondo M, Nagasaki H, Fujiya A, Oiso Y, Hamada Y. Palmitate induces apoptosis in Schwann cells via both ceramide-dependent and independent pathways. Neuroscience, 176: 188-198, 2011.
71.Himeno T, Kamiya H, Naruse K, Harada N, Ozaki N, Seino Y, Shibata T, Kondo M, Kato J, Okawa T, Fukami A, Hamada Y, Inagaki N, Seino Y, Drucker DJ, Oiso Y, Nakamura J. Beneficial effects of exendin-4 on experimental polyneuropathy in diabetic mice. Diabetes 60: 2397-2406, 2011.
このページのトップへ
2010年
72.Miyagi M, Ishii H, Murakami R, Isobe S, Hayashi M, Amano T, Arai K, Yoshikawa D, Ohashi T, Uetani T, Yasuda Y, Matsuo S, Matsubara T, Murohara T: Impact of renal function on coronary plaque composition. Nephrology Dialysis Transplantation, 25:175-181, 2010.
73.Uetani T, Amano T, Kunimura A, Kumagai S, Ando H, Yokoi K, Yoshida T, Kato B, Kato M, Marui N, Nanki M, Matsubara T, Ishii H, Izawa H, Murohara T: The association between plaque characterization by CT angiography and post-procedural myocardial infarction in patients with elective stent implantation. Journal of American College of Cardiology: Cardiovascular Imaging, 3:19-28, 2010.
74.Asano H, Izawa H, Nagata K, Nakatochi M, Kobayashi A, Hirashiki A, Shintani S, Nishizawa T, Tanimura D, Naruse K, Matsubara T, Murohara T, Yokota M: Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population. Diabetologia, 53:234-246, 2010.
75.Ishii H, Kumada Y, Toriyama T, Aoyama T, Takahashi H, Tanaka M, Kamoi D, Kawamura Y, Yamada S, Hayashi M, Yasuda Y, Yuzawa Y, Maruyama S, Matsuo S, Matsubara T, Murohara T: Effects of oral cilostazol 100 mg BID on long-term patency after percutaneous transluminal angioplasty in patients with femoropopliteal disease undergoing hemodialysis: a retrospective chart review in Japanese patients. Clinical Therapeutics, 32:24-33, 2010.
76.Koyasu M, Ishii H, Watarai M, Takemoto K, Inden Y, Takeshita K, Amano T, Yoshikawa D, Matsubara T, Murohara T: Impact of acarbose on carotid intima-media thickness in patients with newly diagnosed impaired glucose tolerance or mild type 2 diabetes mellitus: A one-year, prospective, randomized, open-label, parallel-group study in Japanese adults with established coronary artery disease. Clinical Therapeutics, 32:1610-1617, 2010.
77.Yamada S, Ishii H, Takahashi H, Aoyama T, Morita Y, Kasuga H, Kimura K, Ito Y, Takahashi R, Toriyama T, Yasuda Y, Hayashi M, Kamiya H, Yuzawa Y, Maruyama S, Matsuo S, Matsubara T, Murohara T: Prognostic value of reduced left ventricular ejection fraction at start of hemodialysis therapy on cardiovascular and all-cause mortality in end-stage renal disease patients. Clinical Journal of American Society of Nephrology, 5:1793-1798, 2010.
78.Arai K, Ishii H, Amano T, Uetani T, Nanki M, Marui N, Kato M, Yokoi K, Ando H, Kumagai S, Harada K, Yoshikawa D, Ohshima S, Matsubara T, Murohara T: Volumetric analysis of coronary plaque characterization in patients with metabolic syndrome using 64-slice multi-detector computed tomography. Circulation Journal, 74:2146-2151, 2010.
79.Nakashima E, Watarai A, Tsukahara T, Hamada Y, Naruse K, Kamiya H, Kato J, Kato N, Tomita M, Oiso Y, Nakamura J:Association of resistin polymorphism, its serum levels and prevalence of stroke in Japanese type 2 diabetic patients. Journal of Diabetes Investigation 1: 154‐158, 2010.
80.Ishii H, Nishio M, Takahashi H, Aoyama T, Tanaka M, Toriyama T, Tamaki T, Yoshikawa D, Hayashi M, Amano T, Matsubara T, Murohara T: Comparison of atorvastatin 5 and 20 mg/d for reducing F-18 fluorodeoxyglucose uptake in atherosclerotic plaques on positron emission tomography/computed tomography: A randomized, investigator-blinded, open-label, 6-month study in Japanese adults scheduled for percutaneous coronary intervention. Clinical Therapeutics 32:2337-2347, 2010.
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