九州大学 研究者情報
発表一覧
中川 和憲(なかがわ かずのり) データ更新日:2023.12.07

講師 /  医学研究院 基礎医学部門 病態制御学講座


学会発表等
1. Soichiro Henmi, So Izumi, Reiko Kanno, Masato Hoshino, Kazunori NAKAGAWA, Yutaka Nakashima, Kenji Okada, Takuro Tsukube, Impact of HighResolution Epiaortic Ultrasonographic Imaging on Evaluating Aortic Wall Pathology, The American Heart Association's 2021 Scientific Sessions and Resuscitation Science Symposium, 2021.11.
2. Tsukube T Yokawa K Nakai C, Hoshino M, Yagi N, Nakagawa K, Nakashima Y., Synchrotron-based 4D-X-ray Phase Tomography of Fresh Aortic Wall of Acute Aortic Dissection, The American Heart Association's 2019 Scientific Sessions of the American-Heart-Association, 2019.11, [URL], Backgrounds: Mechanisms of onset of acute aortic dissection (AAD) has not been fully elucidated. Synchrotron-based X-ray phase tomography (XPCT) is a powerful tool to measure biological soft tissues. Recently, we have developed dynamic X-ray phase tomography (4D-XPCT) to discuss the dynamic phenomena of biological samples quantitatively and applied to aortic wall of type-A AAD (AADA).

Material & Methods: The X-ray energy for 4D XPCT was set to 25keV. The effective pixel size was 15.5[mu]m. Fresh ring-shaped aorta obtained during aortic repair for AADA were measured in the specially designed container filled with normal cold saline within 48 hours after surgery (shown in Fig-a). Number of samples was 7. The aorta installed on the sample stage was stretched by hooks, step by step, by 2 mm per step with a five-step phase stepping during a phase tomographic measurement. The amount of stretch was 10mm. In this measurement, number of projections was 600 and exposure time was 500 ms per image and the total measurement time was 38 minutes. The middle part of the aorta between the hooks was imaged. To evaluate the morphological change quantitatively, the mass density was estimated at each step.

Results: X-ray phase tomographic images of aortic wall before stretching and at the stretched conditions, stretching by 2mm, 6mm and 10mm, are shown in 3D findings of Fig-(b). There was a 15.7% reduction in wall thickness of the aorta at end of stretching. The load applied to the sample and change of the densities obtained from tomography during stretching are shown in 2D findings of Fig-(b) and -(c). During aortic wall were stretched and became thinner, density of the aortic media of AADA was not changed.

Conclusions: This result demonstrated that the 4D-XPCT had a capability to trace the detail of deformation process in the biological soft tissues. Mechanical property of the aortic wall of aortic dissection were different from intact aorta during stretching..
3. Yamamoto T, Okada K, Yagi N, Hoshino M, Nakashima Y, Nakagawa K, Tsukube T., Mechanism of Aneurysm Expansion After Endovascular Aortic Repair Analyzed With X-Ray Phase-Contrast Tomography, The American Heart Association's 2018 Scientific Sessions and Resuscitation Science Symposium, 2018.11, [URL].
4. K. Yokawa, T. Tsukube, N. Yagi, M. Hoshino, Y. Nakashima, K. Nakagawa, Y. Okita, Quantitative and Dynamic Measurements of Aortic Wall of Acute Type-A Aortic Dissection With X-Ray Phase-Contrast Tomography, The American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology/Peripheral Vascular Disease 2017 Scientific Sessions, 2017.05, [URL].
5. K. Yokawa, T. Tsukube, N. Yagi, M. Hoshino, Y. Nakashima, K. Nakagawa, Y. Okita, Degeneration of Tunica Media in Acute Type-a Aortic Dissection From X-ray Phase-contrast Tomography, American Heart Association Scientific Session 2017, 2017.10, [URL].
6. K. Yokawa, T. Tsukube, N. Yagi, M. Hoshino, Y. Nakashima, K. Nakagawa, Y. Okita, Quantitative and Dynamic Measurements of Aortic Wall of Acute Type-A Aortic Dissection with X-ray Phase-contrast Tomography, 31st European Association for Cardio-Thoracic Surgery Annual Meeting, 2017.10.
7. Shuichi Hashimoto, Koichi Takayama, 中川 和憲, Hidenori Shiraha, Yoichi Nakanishi, Stem Cell Marker Lgr6 Expression Analysis in Lung and Oral Cancers, The 23rd General Meeting of the Japanese Association for Dental Science, 2016.10, The signal from R-spondin via Lgr6(leucine-rich repeat containing, G protein-coupled receptor 6), a stem cell marker, augments Wnt/β-catenin signaling pathway. We obtained the results that Lgr6 was specifically expressed in the neoplastic cells in lung and oral carcinomas. Some mutations of Lgr6 were also found in some lung carcinoma cell lines. These results suggest that Lgr6 plays an important role for carcinogenesis or development of lung and oral carcinomas..
8. 築部卓郎, 八木直人, 星野真人, 中島 豊, 中川 和憲, 原口知則, 岡田泰司, 中井史, 大北 裕, 大動脈解離の発生機序に関する研究 - 位相差X線CT法および超音波検査法による大動脈壁微細構造の検討 -, 第69回日本胸部外科学会定期学術集会, 2016.09, 【目的】大動脈疾患は近年の治療法の進歩により予後の改善が期待できるようになったが、「大動脈解離がなぜ起こるのか?」については十分 に解明されていない。そこで大動脈壁の微細構造を検討する目的で、大型放射光施設(SPring-8) の位相差X線CT 法(PCXI)ならびに高分解能(18MHz)超音波検査装置を用いて解析を行った。【方法】手術時に採取された上行大動脈の切除標本を用いた。内訳はMarfan 症候群4 例、Non-Marfan の急性解離 20 例、正常大動脈10 例(剖検例)。ホルマリン固定あるいは新鮮(手術直後に計測)標本をPCXI による二次元 (2D) ならびに三次元(3D) 解析ならに超音波検査(18MHz) を行った。PCXI の画像は従来の病理切片画像とは異なり、タンパク質密度を正確に反映しているため定量的に分析し、その後、病理組織学的に検討した。【成績】正常標本ではPCXI では中膜の密度はほぼ均一であり、弾性線維、膠原線維の分布所見と一致した。Marfan に急性解離合併例では、解離部分および非解離部分においても内膜側と外膜側に密度差を認めた。さらに解離が及んでいない中膜内においても 解離に連続して低密度層状構造と嚢胞中膜壊死像がみられた( 図1)。Non-Marfan 急性解離標本では非解離部分の中膜内密度は不整で弾性線維の不均一分布と一致し層状に組織密度に有意差を認め、同一標本の超音波検査でも同様の所見が得られた。【結論】位相差X 線CT 法により大動脈壁 の微細構造が三次元で観察可能であった。大動脈解離例ではMarfan 症候群の有無にかかわらず非解離部分の中膜において弾性線維の構造に異常がみられたことより、急性大動脈解離例では発症前からあらかじめ大動脈壁の中膜構造に変化を来たしており、中膜の弾性線維層の構造異常を伴う病態であると考えられる。また、超音波検査所見でも同様の所見が得られたことより、大動脈壁のスクリーニング検査による大動脈解離発症前の予知診断の可能性が示唆された。.
9. T. Tsukube, N. Yagi, M. Hoshino, Y. Nakashima, K. Nakagawa, Y. Okada, T. Haraguchi, M. Yoshida, N. Mukohara, S. Kozawa, K. Ogawa, Y. Okita, Impact of synchrotron radiation based phase-contrast X-ray CT findings on understanding onset of acute aortic dissection., American Association for Thoracic Surgery, Aortic Symposium Workshop 2015, 2015.10.
10. Kazunori Nakagawa, Hiroshi Fujii, Yutaka Nakashima, PATHOGENESIS OF EARLY AND INTERMEDIATE LESIONS OF HUMAN CORONARY ATHEROSCLEROSIS: ACCUMULATION OF PLASMA-DERIVED LIPIDS AND DISPERSION
OF SMOOTH MUSCLE CELLS., The 11th International Congress on Coronary Artery Disease, 2015.11.
11. 中川 和憲, 中島豊, ヒトの冠状動脈硬化における前粥腫病変(preatheroma, intermediate lesion)の発生病理:
内膜の脂質沈着と内膜平滑筋細胞の分散

, 第21回 九州血液血管研究会, 2014.11.
12. Kazunori Nakagawa, Hiroshi Fujii, Yutaka Nakashima, Pathogenesis of intermediate lesion of human coronary atherosclerosis: Lipid pool formation without necrosis and dispersion of intimal smooth muscle cells., The 82nd Annual Congress of The European Atherosclerosis Society, 2014.06, Aim: Proliferation of smooth muscle cells (SMCs) and deposition of lipids by death of macrophage foam cells are key events in atherosclerosis in animal models. However, different processes occur in human atherosclerosis. The purpose of this study is to clarify the pathogenesis of intermediated lesion (preatheroma) of human atherosclerosis, focusing on intimal SMCs and extracellular lipids.
Methods and Results: Step and serial frozen sections of the right coronary artery were obtained from 43 Japanese autopsied subjects (from 15 to 49 years of age) with no or earlier atherosclerotic lesions. The lesions were classified into 4 categories according to the grade of atherosclerosis; diffuse intimal thickening (DIT), initial lesion, foam cell lesion and intermediate lesion. DIT is a physiological intimal thickening with plenty of SMCs and no lipid deposition. Initial lesions and foam cell lesions exhibited mild deposition of extracellular lipids and accumulation of macrophage foam cells in the SMC-rich intima, respectively. Intermediate lesions consisted of lipid pools with abundant extracellular lipids in the thickened intima, in addition to many SMCs and macrophage foam cells. No necrosis or lytic changes were observed in the lipid pools, and the extracellular lipids colocalized with ApoB and fibrinogen, suggesting that the penetration of plasma lipoproteins play an important role in lipid pool formation. The density of intimal SMCs was significantly decreased in the foam cell lesion and the intermediate lesion, but the number of the cells showed no significant change. No MIB-1-positive cells or TUNEL-positive cells were observed, and only a few SMCs showed positive immunostain for BAX, LC3B and NLRP3, suggesting that SMCs were spread out in the intima as the lesion progressed without undergoing excessive proliferation or death.
Conclusion: Intermediate lesion of human atherosclerosis develops primarily by infiltration of plasma lipoproteins and lipid pool formation, and dispersion of pre-existing intimal SMCs..
13. Takuro Tsukube, Naoto Yagi, Masato Hoshino, Kentaro Uesugi, Yutaka Nakashima, Kazunori Nakagawa, Katsuhiko Nakamae, Tomonori Haraguchi, Ritsu Matsukawa, Shuichi Kozawa, Yutaka Okita, Acute Aortic Dissection is Associated with Alteration of Elastic Architecture of Aortic Media Assessed by Synchrotron Phase-Contrast X-ray Computed Tomography., 第78回日本循環器学会学術集会, 2014.03, Objectives: To investigate alteration of the elastic architecture of the media of aortic dissection, we have applied synchrotron phase-contrast X-ray computed tomography imaging (PCXI) to provide detailed two and three-dimensional visualization of aortic wall structures in excised human aorta. Methods: Human aortic walls of the ascending aorta were obtained during aortic replacement, including aortic dissection (group-A: n=17) and Marfan syndrome (group-M: n=3). Normal aorta was obtained from autopsy (group-N: n=3). Ex vivo PCXI was performed using a synchrotron radiation source (SPring-8), and samples were also histologically analyzed. Results: In all samples, unprecedented structural contrast and resolution were obtained. In group-N, PCXI revealed minimal changes in density of media. In group-M, PCXI demonstrated bimodal peaks in density and intra-medial low density zone was connected to cystic medial necrosis and aortic dissection. In group-A, PCXI revealed low density area in the outer layer of the media of the non-dissecting part of the aortic wall, which were well correlated with irregularity of the elastic layers. The mass density of media in group-A and M were significantly lower than normal aorta.Conclusions: PCXI revealed details about the spatial relationships of the elastic architecture in the aortic wall. These findings may indicate that changes in elastic architecture of the media are initial presentations, prior to onset of acute aortic dissection..
14. 中川 和憲, ヒトの冠状動脈硬化における前粥腫病変(intermediate lesion)の発生病理:Lipid
poolの形成と内膜平滑筋細胞の分散
, 2013年度九大病理研究会, 2013.12.
15. 築部卓郎, 八木直人, 星野真人, 中島 豊, 中川 和憲, 原口知則, 松川 律, 小澤修一, 小川恭一, 中前勝彦, 大北 裕, 大動脈解離はなぜ起こるのか?-位相差X線CT法による大動脈壁微細構造の研究-, 第66回日本胸部外科学会定期学術集会, 2013.10, 【目的】大動脈解離は近年の治療法の進歩により予後の改善が期待できるようになった。しかしながら、未だ「大
動脈解離がなぜ起こるのか?」については十分に解明されていないのが現状である。そこで大動脈壁の微細構造
を検討する目的で、大型放射光施設(SPring-8)の位相差X 線CT 法(PCXI)を用いて解析を行った。PCXI は密度
分解能が高く、特にX 線吸収が少ないソフトマテリアルの解析に有効な点に着目し、大動脈壁構造の解析に初め
て応用した。【方法】手術時に採取された上行大動脈の切除標本を用いた。標本の内訳はMarfan 症候群4 例(うち
急性解離2 例)、Non-Marfan の急性解離12 例、真性瘤10 例で、さらに正常大動脈2 例(剖検例)であった。ホル
マリン固定後PCXI による二次元 (2D)ならびに三次元(3D)解析を行った。PCXI の画像は従来の病理切片画像
とは異なり、タンパク質密度を正確に反映しているため定量的に分析した。その後、切片を作成し病理組織学的
に検討した。【成績】正常標本ではPCXI では中膜の密度はほぼ均一であり、弾性線維、膠原線維の分布所見と一致
した。Marfan に急性解離合併例では、解離部分および非解離部分においても内膜側と外膜側に密度差を認めた。
さらに解離が及んでいない中膜内においても解離に連続して低密度層状構造と嚢胞中膜壊死像がみられた(図1:
左上;固定標本、左下;膠原線維分布、右上;PCXI 2D 像、右下;PCXI 3D 像)。Non-Marfan 例においても、非解離部
分の中膜内密度は不整で弾性線維の不均一分布と一致した。【結論】位相差X 線CT 法により大動脈壁の微細構造が
三次元で観察可能であった。Marfan 症候群の有無にかかわらず非解離部分の中膜において弾性線維の構造に異常
がみられたことより、急性大動脈解離例では発症前からあらかじめ大動脈壁の中膜構造に変化を来たしているこ
とが明らかとなった。以上より、急性大動脈解離は中膜の弾性線維層の構造異常を伴う病態であると考えられる。.
16. 中川 和憲, 中島 豊, ヒトの冠状動脈硬化における前粥腫病変(preatheroma, intermediate lesion)の発生病理:内膜の脂肪沈着と内膜平滑筋細胞の密度の低下, 第45回日本動脈硬化学会学術集会, 2013.07, 我々は以前、ヒトの冠状動脈硬化における早期の泡沫細胞病変の形成に、びまん性内膜肥厚(DIT)への脂肪の沈着とマクロファージの浸潤が重要であることを明らかにした。今回は次の段階である前粥腫病変の成り立ちに注目し、15歳から49歳までの剖検例の右冠状動脈の凍結切片を用いて組織学的に検討した。その結果、前粥腫病変においては内膜の肥厚、脂肪沈着の増加、泡沫細胞の増加、内膜平滑筋細胞の密度の低下を認めた(図)。一方、内膜平滑筋細胞の数はDITや早期病変と比較して有意な相違は見られなかった。以上のようにヒトのアテローム性動脈硬化の早期・中期病変においては、内膜平滑筋細胞の数よりも密度に変化が認められた。.
17. Takuro Tsukube, Naoto Yagi, Masato Hoshino, Yutaka Nakashima, Kazunori Nakagawa, Katsuhiko Nakamae, Tomonori Haraguchi, Ritsu Matsukawa, Shuichi Kozawa, Yutaka Okita., High-Resolution Visualization of Three-Dimensional Anatomical Imaging in Dissecting Aortic Wall via Synchrotron Phase Contrast X-ray Imaging, 第77回日本循環器学会学術集会, 2013.03.
18. 村上祐介、鬼丸満穂、米満吉和、中川和憲、池田康博、中村誠、矢部武士、長谷川護、石橋達朗、居石克夫, 網膜変性モデル動物におけるpigment epithelium-derived factor (PEDF)の作用に関する病態学的検討, 第97回日本病理学会総会, 2008.05.
19. 鈴木華子、鬼丸満穂、中川和憲、中村誠司、居石克夫, 扁平上皮癌におけるPodoplaninの発現と癌リンパ管新生に関する病理学的検討, 第49回日本脈管学会総会, 2008.10.
20. 村上祐介、鬼丸満穂、米満吉和、中川和憲、池田康博、中村誠、矢部武士、長谷川護、石橋達朗、居石克夫, 網膜変性モデル動物におけるpigment epithelium-derived factor (PEDF)の作用に関する病態学的検討, 第97回日本病理学会総会, 2008.05.
21. 鈴木華子、鬼丸満穂、中川和憲、中村誠司、居石克夫, 扁平上皮癌におけるPodoplaninの発現と癌リンパ管新生に関する病理学的検討, 第97回日本病理学会総会, 2008.05.
22. Murakamia Y, Ikeda Y, Yonemitsu Y, Onimaru M, Nakagawa K, Kohno R, Miyazaki M, Nakamura M, Yabe T, Inoue M, Hasegawa M, Ishibashi T, Sueishi K: , Regulation of mitochondrial release of apoptosis-inducing factor is a mechanism for neuroprotective activity of pigment epithelium-derived factor in retinal degeneration. , ARVO 2008 Annual Meeting, 2008.05.
23. Onimaru M, Yonemitsu Y, Tanii M, Fujii T, Kohno R, Nakano T, Nakagawa K, Nakashima Y, Sueishi K., Paracrine loop between VEGF-C/Flt-4 and PDGF-BB/PDGFR-beta systems contribute therapeutic angiogenesis using FGF-2 gene transfer in ischemic hind limbs., XXth Congress of the International Society on Thrombosis and Haemostasis., 2005.08.
24. Jin CH, Yonemitsu Y, Nagata S, Kohno R, Tsutsumi N, Sata S, Hashimoto R, Nakagawa K, Okano S, Sueishi K., Flk-1 identifies pluripotent precursor in fetal mous liver., XIIIth International Vascular Biology Meeting., 2004.06.
25. Onimaru M, Yonemitsu Y, Tanii M, Tsutsumi N, Nakagawa K, Nakashima Y, Sueishi K. , Fibroblast growth factor-2(FGF-2) gene transfer can stimulate endogenous PDGF-B mRNA via VEGF-C/Flt-4 system in murine ischemic hind limbs., XIIIth International Vascular Biology Meeting., 2004.06.
26. Onimaru M, Yonemitsu Y, Tanii M, Tsutsumi T, Nakagawa K, nakashima Y, and Sueishi K, Involvement of VEGF-C/flt-4 system in therapeutic angiogenesis of FGF-2 gene transfer in murine ischemic hind limb., XIX CONGRESS of The International Society on Thrombosis and Haemostasis, 2003.07.
27. ISHIBASHI H, NAKAGAWA K, ONIMARU M, KAWAMURA R, SHIRASUNA K, SUEISHI K., Inhibition of Tissue Factor Synthesis by Antisense Transfection Suppresses Tissue Factor / Factor VIIa - induced uPAR Upregulation, XVIII Congress of The International Society on Thrombosis and Haemostasis, 2001.07.
28. 米満吉和、中川和憲、中島豊、鬼丸満穂、真崎一郎、谷井貢、居石克夫, 血管新生遺伝子治療における「血管新生因子作用機構の階層性」と「"Integrated" Therapeutic Angiogenesis」の提唱, 第42回日本脈管学会総会, 2001.11.
29. Masaki I, Yonemitsu Y, Sata S, Komori K, Nakagawa K, Fukumura M, Hou X, Nagai Y, Hasegawa M, Sugimachi K, Sueishi K, Highly efficient intramuscular gene transfer using Sendai virus vector: VEGF is necessary, but seriously toxic without FGF-2 to treat critical limb ischemia., 第7回日本遺伝子治療学会総会, 2001.07.
30. Ohta R, Yonemitsu Y, Shoji F, Nakagawa K, Nishizaki T, Sugimachi K, Sueishi K., Slight increase of serum ceruloplasmin via somatic hepatocyte transplantation is sufficient to improve the prognosis of rat model of Wilson's disease., 4th Annual Meeting American Society of Gene Therapy, 2001.06.
31. Yonemitsu Y, Masaki I, Sata S, Komori K, Nakagawa K, Fukumura M, Hou X, Nagai Y, Hasegawa M, Sugimachi K, Sueishi K., Serious adverse effect of intramuscular gene transfer of VEGF165 for limb salvage in mice with critical limb ischemia., 4th Annual Meeting American Society of Gene Therapy.
32. Fujimoto H, Yonemitsu Y, Ferrari S, Kitson C, Ueno H, Nakagawa K, Nakashima Y, Fukumura M, Nagai Y, Geddes D, Alton E, Hasegawa M., Rapid and efficient uptake of sendai virus vector via apical membrane results in efficient airway gene transfer., The Eighth Meeting of the Europian Society of Gene Therapy, 2000.10.

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