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医学部 医学科 解剖学講座超微形態科学分野 |
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職名 |
准教授 |
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外部リンク |
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関連SDGs |
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論文 【 表示 ／ 非表示 】
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SETDB1-Mediated Chromatin Regulation in Intestinal Epithelial Cells During Intestinal Ischemia-Reperfusion Injury. 査読あり
Higuchi K, Ikenoue M, Ishizuka T, Kai K, Takahashi N, Kubota T, Shirouzu S, Lkham-Erdene B, Aung KM, Nakai M, Sawaguchi A, Nanashima A, Hishikawa Y
Acta histochemica et cytochemica 58 ( 1 ) 9 - 18 2025年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本組織細胞化学会
SET domain bifurcated 1 (SETDB1), a histone H3K9-specific methyltransferase, is crucial for heterochromatin formation and intestinal homeostasis, but its role in intestinal ischemia-reperfusion injury (IRI) remains unclear. This study investigated changes in SETDB1-mediated nuclear chromatin regulation in intestinal epithelial cells (IECs) using an IRI mouse model. Jejunal samples were collected after 75 min of ischemia followed by 24 hr of reperfusion. Sinefungin was administered as a histone methyltransferase inhibitor. Morphologic changes were evaluated using hematoxylin-eosin staining and electron microscopy, and cell-adhesion molecule expression, including ZO-1, E-cadherin, integrin-β4, and laminin, was evaluated using immunohistochemistry. Super-resolution microscopy analyzed intranuclear SETDB1 localization and heterochromatin formation in IECs. IRI-affected jejunum exhibited massive IEC detachment, dilated intercellular spaces, basement membrane damage, and decreased expression of E-cadherin and integrin-β4. Sinefungin prevented these changes, however. The proportion of IECs expressing nuclear SETDB1 throughout the euchromatin was significantly higher in IRI-affected jejunum (77.8%) than sham-treated (3.0%) or sinefungin-treated, IRI-affected jejunum (2.7%). The proportion of IECs with decreased heterochromatin was significantly higher in sinefungin-treated, IRI-affected jejunum (84.3%) than untreated IRI-affected jejunum (15.6%). These findings suggest that SETDB1-mediated chromatin regulation is pivotal in intestinal IRI and represents a potential therapeutic target.
DOI： 10.1267/ahc.24-00061
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Imazato H., Takahashi N., Hirakawa Y., Yamaguchi Y., Hiyoshi M., Tajima T., Chosa E., Sawaguchi A.
Scientific Reports 13 ( 1 ) 6352 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Recent physiological studies have shown that the deep fascia has received much attention concerning clinical medicine; however, histological examination of the deep fascia has not been well established. In this study, we aimed to clarify and visualize the structure of the deep fascia by taking advantage of cryofixation techniques and low-vacuum scanning electron microscopy. As a result, the ultrastructural observations revealed three-dimensional stratification of the deep fascia composed of three layers: the first superficial layer consisting of collagen fibers extending in various directions with blood vessels and peripheral nerves; the second intermediate layer formed by single straight and thick collagen fibers with flexibility; and the third deepest layer, consisting of relatively straight and thin collagen fibers. We explored the use of two hooks to hold a piece of deep fascia in place through the course of cryo-fixation. A comparative observation with or without the hook-holding procedure would indicate the morphological adaptation to physiological stretch and contraction of the deep fascia. The present morphological approach paves the way to visualize three-dimensional ultrastructures for future biomedical studies including clinical pathophysiology.
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Insertion sites of the muscles attached to the clavicle: a cadaveric study of the clavicle 査読あり
Imazato H., Takahashi N., Sawaguchi A., Hirakawa Y., Yamaguchi Y., Hiyoshi M., Tajima T., Chosa E.
BMC Musculoskeletal Disorders 24 ( 1 ) 160 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Musculoskeletal Disorders
Background: Clavicle fractures are common injuries, especially in young, active individuals. Operative treatment is recommended for completely displaced clavicle shaft fractures, and plate fixation is stronger than the use of intramedullary nails. Few studies have reported on iatrogenic injuries to the muscle attached to the clavicle during fracture surgery. The aim of this study was to clarify the area of the insertion sites of muscles attached to the clavicle in Japanese cadavers using gross anatomy and three-dimensional (3D) analysis. We also aimed to compare the effects of anterior plate templating and superior plate templating on clavicle shaft fractures using 3D images. Methods: Thirty-eight clavicles from Japanese cadavers were analyzed. We removed all clavicles to identify the insertion sites and measured the size of the insertion area of each muscle. Three-dimensional templating was performed on both the superior and anterior plates of the clavicle using data obtained from computed tomography. The areas covered by these plates on the muscles attached to the clavicle were compared. Histological examination was performed on four randomly selected specimens. Results: The sternocleidomastoid muscle was attached proximally and superiorly; the trapezius muscle was attached posteriorly and partly superiorly; and the pectoralis major muscle and deltoid muscles were attached anteriorly and partially superiorly. The non-attachment area was located mainly in the posterosuperior part of the clavicle. It was difficult to distinguish the borders of the periosteum and pectoralis major muscles. The anterior plate covered a significantly broader area (mean 6.94 ± 1.36 cm2) of the muscles attached to the clavicle than did the superior plate (mean 4.11 ± 1.52 cm2) (p < 0.0001). On microscopy, these muscles were inserted directly into the periosteum. Conclusion: Most of the pectoralis major and deltoid muscles were attached anteriorly. The non-attachment area was located mainly from the superior to posterior part of the clavicle midshaft. Both macroscopically and microscopically, the boundaries between the periosteum and these muscles were difficult to demarcate. The anterior plate covered a significantly broader area of the muscles attached to the clavicle than that by the superior plate.
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A Suggested Mechanism for Green Discoloration of the Postmortem Brain 査読あり
Shinkawa N., Takahashi N., Yano K., Sawaguchi A., Sonoda A., Kakizaki E., Yukawa N.
American Journal of Forensic Medicine and Pathology 44 ( 2 ) 132 - 135 2023年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Forensic Medicine and Pathology
In the putrefied brain, the cortex and basal ganglia show dark-grayish to green discoloration due to sulfhemoglobin formed from hydrogen sulfide (H2S) produced by endogenous bacteria and hemoglobin. In this study, we propose and demonstrate another mechanism of green discoloration in the brain. The formalin-fixed brain of a cadaver donated for medical education with no putrefaction was used. Half of the brain was immersed in sodium hydrosulfide solution, to imitate the H2S produced by bacteria. This half showed greenish discoloration, mainly in the basal ganglia and cortex. The other half showed positive Perls' Prussian blue staining, mainly in the basal ganglia and cortex. The area of greenish discoloration due to H2S and the region positive for Perls' Prussian blue staining coincided. Tissue treatment with strong oxidizing agents is required to liberate heme iron. The positive Perls' Prussian blue staining in this study thus does not reflect heme iron. In conclusion, we considered that non-heme iron compounds physiologically present in the brain and H2S represent sources of putrefactive greenish discoloration in the brain.
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In situ strategy for biomedical target localization via nanogold nucleation and secondary growth
Sawaguchi A., Kamimura T., Takahashi N., Yamashita A., Asada Y., Imazato H., Aoyama F., Wakui A., Sato T., Choijookhuu N., Hishikawa Y.
Communications Biology 4 ( 1 ) 710 2021年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Communications Biology
Immunocytochemistry visualizes the exact spatial location of target molecules. The most common strategy for ultrastructural immunocytochemistry is the conjugation of nanogold particles to antibodies as probes. However, conventional nanogold labelling requires time-consuming nanogold probe preparation and ultrathin sectioning of cell/tissue samples. Here, we introduce an in situ strategy involving nanogold nucleation in immunoenzymatic products on universal paraffin/cryostat sections and provide unique insight into nanogold development under hot-humid air conditions. Nanogold particles were specifically localized on kidney podocytes to target synaptopodin. Transmission electron microscopy revealed secondary growth and self-assembly that could be experimentally controlled by bovine serum albumin stabilization and phosphate-buffered saline acceleration. Valuable retrospective nanogold labelling for gastric H+/K+-ATPase was achieved on vintage immunoenzymatic deposits after a long lapse of 15 years (i.e., 15-year-old deposits). The present in situ nanogold labelling is anticipated to fill the gap between light and electron microscopy to correlate cell/tissue structure and function.
MISC 【 表示 ／ 非表示 】
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Primary pulmonary angiosarcoma: A case report.
Hiroyuki Tanaka, Kenji Yorita, Nobuyasu Takahashi, Yasuhiro Usuma, Kunihide Nakamura and Hiroaki Kataoka
Pathology international 65 ( 10 ) 554 - 557 2015年8月
記述言語：英語 掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議） 出版者・発行元：WILEY-BLACKWELL
DOI： 10.1111/pin.12341
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Synchronous solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm of the pancreas: report of a case.
"NAOYA IMAMURA, KAZUO CHIJIIWA, JIRO OHUCHIDA, MASAHIDE HIYOSHI, NOBUYASU TAKAHASHI, KENJI YORITA,
Surgery Today 41 ( 6 ) 865 - 871 2011年6月
記述言語：英語 掲載種別：記事・総説・解説・論説等（学術雑誌） 出版者・発行元：Springer
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Enlarged solitary necrotic nodule of the liver misinterpreted （共著）
Otani K, Chijiiwa K, Kondo K, Tsuchimochi M, Takahashi N, Ikenaga N, Ohuchida J,
Clinical Journal of Gastroenterology 2 ( 5 ) 355 - 360 2009年5月
記述言語：英語 掲載種別：記事・総説・解説・論説等（学術雑誌） 出版者・発行元：Clinical Journal of Gastroenterology
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外傷性肝細胞癌破裂に対し肝動脈塞栓術を施行後切除した1例（共著）
新名一郎, 千々岩一男, 近藤千博, 永野元章, 内山周一郎, 高橋伸育, 片岡寛章
日本消化器外科学会雑誌 2008年9月
記述言語：日本語 掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議） 出版者・発行元：日本消化器外科学会雑誌
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Activation of MET receptor tyrosine kinase in ulcer surface epithelial cells undergoing restitution
Nagai M., Takahashi N., Miyazawa K., Kawaguchi M., Chijiiwa K., Kataoka H.
Pathology International 58 ( 7 ) 462 - 464 2008年7月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（大学・研究所紀要） 出版者・発行元：Pathology International
講演・口頭発表等 【 表示 ／ 非表示 】
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グリオキサール系・ホルマリン代替固定液・ALTFixⓇを用いた灌流固定ラットの早期における固定性の評価
豊嶋（青山）典世、高橋伸育、澤口 朗
第125回日本解剖学会総会全国学術集会
開催年月日： 2020年3月25日 - 2020年3月27日
記述言語：日本語 会議種別：口頭発表（一般）
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光顕用切片の標的物質局在をナノスケールで可視化する新たな免疫電顕解析技術と再生臓器開発・評価への応用
澤口 朗、上村 健、菱川善隆、山下 篤、豊嶋典世、髙橋伸育、今里浩之、浅田祐士郎
第19回日本再生医療学会総会
開催年月日： 2020年3月12日 - 2020年3月14日
記述言語：日本語 会議種別：ポスター発表
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グリオキサール系・ホルマリン代替固定液・ALTFixRを用いたラット脳を中心とする固定性の評価
豊嶋（青山）典世、高橋伸育、澤口 朗
第75回日本解剖学会九州支部学術集会
開催年月日： 2019年11月9日
記述言語：日本語 会議種別：口頭発表（一般）
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気相―液層界面法を用いた膵癌細胞株SUIT-2の三次元培養と電顕観察
高橋伸育、青山典世、澤口 朗
第75回日本顕微鏡学会 学術講演会
開催年月日： 2019年6月17日 - 2019年6月19日
記述言語：日本語 会議種別：ポスター発表
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再生臓器開発とその臨床応用に資する簡便な電顕立体解析手法の開発と大容量画像共有クラウドシステムの応用
澤口 朗、高橋伸育、豊嶋典世
第18回日本再生医療学会総会
開催年月日： 2019年3月21日 - 2019年3月23日
記述言語：日本語 会議種別：口頭発表（一般）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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新たな腰痛治療法の開発研究に資する深筋膜及び周辺組織の超微形態解析
研究課題/領域番号：24K12379 2024年04月 - 2027年03月
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
担当区分：研究代表者
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肝様腺癌の病態解明と新規抗体による治療戦略の開発
研究課題/領域番号：18K08686 2019年04月 - 2021年03月
科学研究費補助金 基盤研究(C)
胃癌の特殊型である肝様腺癌は血清AFPの上昇を伴い、通常の胃癌と比較して高率に脈管侵襲や肝転移を起こし、薬剤への抵抗性を示す予後不良の疾患である。その報告は年々増加する一方、生物学的特性については不明な点が多く、研究に有用なツールも不十分である。研究代表者は十二指腸乳頭部を由来とする新規肝様腺癌細胞株の樹立に成功しており、これを用いて浸潤、転移に関わる因子を同定し、有効な治療戦略を確立することが本研究の目的である。Glypican-3 (GPC3)は肝細胞癌に特徴的なマーカーであり、予後不良因子として報告されている。この遺伝子に対する新規抗体gc33を用いた実験では抗体依存性細胞性細胞障害作用を賦活させることにより抗腫瘍効果があることが報告されており、抗体 gc33を肝細胞癌と類似した性質を持つ肝様腺癌に応用することで、予後不良な肝様腺癌の治療法にブレークスルーをもたらすことが期待される。
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肝様腺癌に対する新規抗体を用いた治療戦略
研究課題/領域番号：26461983 2014年04月 - 2017年03月
科学研究費補助金 基盤研究(C)
担当区分：研究代表者
肝様腺癌に対する新規抗体を用いた治療戦略
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膵癌の浸潤、転移に関与するＷｎｔ関連遺伝子の機能解析
研究課題/領域番号：23791552 2011年04月 - 2013年03月
科学研究費補助金 若手研究(B)
担当区分：研究代表者
膵癌の浸潤、転移に関与するＷｎｔ関連遺伝子の機能解析