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Affiliation |
Faculty of Medicine School of Medicine Department of Pathology, Pathophysiology |
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Professor |
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YAMASHITA Atsushi
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Degree 【 display / non-display 】
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medical doctor ( 2004.3 University of Miyazaki )
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学士（医学） ( 1997.3 宮崎大学 )
Research Areas 【 display / non-display 】
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Life Science / Human pathology / PATHOLOGY
Papers 【 display / non-display 】
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Yamashita A., Oda T., Aman M., Wakasa T., Gi T., Ide R., Todo Y., Tamura N., Sato Y., Itoh H., Asada Y.
BJOG: An International Journal of Obstetrics and Gynaecology 2023
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：BJOG: An International Journal of Obstetrics and Gynaecology
Objective: To identify pulmonary/uterine thrombus formation in amniotic fluid embolism (AFE). Design: Retrospective, observational. Setting: Nationwide. Population: Eleven autopsy cases of AFE and control cases. Methods: We assessed pulmonary and uterine thrombus formation and thrombus area in AFE and pulmonary thromboembolism (PTE) as a control. The area of platelet glycoprotein IIb/IIIa, fibrin, neutrophil elastase, citrullinated histone H3 (a neutrophil extracellular trap marker) and mast cell chymase immunopositivity was measured in 90 pulmonary emboli, 15 uterine thrombi and 14 PTE. Main outcome measures: Pathological evidence of thrombus formation and its components in AFE. Results: Amniotic fluid embolism lung showed massive thrombus formation, with or without amniotic emboli in small pulmonary arteries and capillaries. The median pulmonary thrombus size in AFE (median, 0.012 mm2; P < 0.0001) was significantly smaller than that of uterine thrombus in AFE (0.61 mm2) or PTE (29 mm2). The median area of glycoprotein IIb/IIIa immunopositivity in pulmonary thrombi in AFE (39%; P < 0.01) was significantly larger than that of uterine thrombi in AFE (23%) and PTE (15%). The median area of fibrin (0%; P < 0.001) and citrullinated histone H3 (0%; P < 0.01) immunopositivity in pulmonary thrombi in AFE was significantly smaller than in uterine thrombi (fibrin: 26%; citrullinated histone H3: 1.1%) and PTE (fibrin: 42%; citrullinated histone H3: 0.4%). No mast cells were identified in pulmonary thrombi. Conclusions: Amniotic fluid may induce distinct thrombus formation in the uterus and lung. Pulmonary and uterine thrombi formation may contribute to cardiorespiratory collapse and/or consumptive coagulopathy in AFE.
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Histopathological Features of Cancer-Associated Venous Thromboembolism: Presence of Intrathrombus Cancer Cells and Prothrombotic Factors. Reviewed
Gi T, Kuwahara A, Yamashita A, Matsuda S, Maekawa K, Moriguchi-Goto S, Sato Y, Asada Y
Arteriosclerosis, thrombosis, and vascular biology 2022.11
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)
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Expression of fibroblast activation protein-α in human deep vein thrombosis Reviewed
Oguri N., Gi T., Nakamura E., Furukoji E., Goto H., Maekawa K., Tsuji A.B., Nishii R., Aman M., Moriguchi-Goto S., Sakae T., Azuma M., Yamashita A.
Thrombosis Research 241 109075 2024.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
Background: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. Methods: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. Results: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. Conclusions: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.
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Sugita C., Maekawa K., Gi T., Oguri N., Nakamura E., Furukoji E., Azuma M., Asada Y., Yamashita A.
Thrombosis Research 238 185 - 196 2024.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
Background: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. Aims: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. Methods and results: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. Conclusions: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
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Nishino S., Nishimura M., Asada Y., Yamashita A., Shibata Y.
European Heart Journal - Case Reports 8 ( 4 ) ytae178 2024.4
Language：English Publishing type：Research paper (scientific journal) Publisher：European Heart Journal - Case Reports
Background Aortic regurgitation (AR) associated with detachment of the aortic valve commissure is extremely rare. We present a case of progressively worsening severe chronic AR due to detachment of the aortic valve commissure during hospitalization that was confirmed with multimodality imaging. Case summary A 50-year-old male with Marfan syndrome visited our hospital to receive treatment for cholelithiasis. Pre-operative examination revealed severe AR and aortic root aneurysm. Because the patient was asymptomatic, it was decided that cholecystectomy should be performed first. However, the patient’s heart failure worsened acutely when his blood pressure increased just before induction of anaesthesia. The patient required intubation and management of heart failure. Five days later, the patient underwent cholecystectomy. He was treated for heart failure and underwent open heart surgery on the 35th hospital day. Intraoperative transoesophageal echocardiography revealed that his AR was caused by both enlargement of the aortic root and localized dissection of the aortic valve commissure, which was supported by intraoperative findings and histopathological evaluation. Aortic regurgitation was exacerbated by a new localized dissection, resulting in acute worsening of heart failure. Discussion Aortic valve commissure detachment can easily lead to sudden onset of severe AR, deteriorating haemodynamics, and acute pulmonary oedema. Since delayed medical treatment leads to poor clinical outcomes, prompt and accurate diagnosis and appropriately timed surgical intervention are essential. This very rare case of severe AR worsening due to spontaneous aortic valve commissure dissection was evaluated with multiple modalities during hospitalization. Understanding this clinical condition will help cardiologists provide better medical care.
Books 【 display / non-display 】
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モデル動物の作製と利用. 循環器疾患
山下 篤、大栗伸行、浅田祐士郎（ Role： Joint author , 深部静脈血栓モデル）
エル・アイ・シー. 2021.9
Language：Japanese Book type：Scholarly book
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モデル動物の作製と利用. 循環器疾患
山下 篤、魏 峻洸、浅田祐士郎（ Role： Joint author , ウサギ反復傷害血栓モデル）
エル・アイ・シー 2021.9
Language：Japanese Book type：Scholarly book
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New Textbook of Clinical Phlebology
（ Role： Contributor）
2019.10
Language：Japanese
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Thrombosis, atherosclerosis and atherothrombosis: New insights and experimental protocols
Yamashita A, Asada Y（ Role： Joint author）
Intech 2015.12
Language：English Book type：Scholarly book
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Traditional and novel risk factors in atherothrombosis
Atsushi Yamashita, Yujiro Asada（ Role： Joint author）
Intech 2012.4
Language：English Book type：Scholarly book
MISC 【 display / non-display 】
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Maekawa K., Nagayasu E., Hata Y., Hanamure F., Maruyama H., Yamashita A.
Pathology International 73 ( 8 ) 373 - 376 2023.8
Language：English Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：Pathology International
DOI： 10.1111/pin.13352
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冠動脈血栓の病理 Invited
山下 篤、西平賢作、浅田祐士郎
病理と臨床 39 ( 11 ) 1099 - 1105 2021.11
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
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ウサギ：ヒトの動脈硬化をウサギで再現 Invited
山下 篤、浅田祐士郎
医学のあゆみ 279 ( 2 ) 169 - 175 2021.10
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
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脳梗塞の血管・血栓病理と血栓の形成機序 Invited
山下 篤、浅田祐士郎
Brain and Nerve 73 ( 9 ) 965 - 974 2021.9
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
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アテローム血栓症における血栓形成機序はどこまでわかったのか？ Invited
山下 篤、浅田祐士郎
Heart View 25 ( 1 ) 32 - 38 2021.1
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
Presentations 【 display / non-display 】
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血栓症の発症に繋がる血栓の発生および成長機序の解明
山下 篤
第67回日本病理学会秋期特別総会 2021.11.4
Event date： 2021.11.4 - 2021.11.5
Language：Japanese Presentation type：Oral presentation (invited, special)
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Detection and safety prevention of deep vein thrombosis Invited International conference
Atsushi Yamashita
The 19th International symposium on atherosclerosis 2021.10.26
Event date： 2021.10.24 - 2021.10.27
Language：English Presentation type：Symposium, workshop panel (nominated)
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破裂性冠動脈プラークの病理とモデル動物のPETイメージング Invited
山下 篤
第53回日本動脈硬化学会総会 2021.10.23
Event date： 2021.10.23 - 2021.10.24
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
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静脈血栓症の病理 Invited
山下 篤
第43回日本血栓止血学会 2021.5.29
Event date： 2021.5.28 - 2021.5.31
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
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Histopathological features of cancer-associated venous thromboembolism in human International conference
Gi T, Yamashita A, Matsuda S, Sato Y, Asada Y.
ISTH 2020 Virtual Congress,
Event date： 2020.7.13 - 2020.7.14
Language：English Presentation type：Poster presentation
Awards 【 display / non-display 】
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日本病理学会学術研究賞
2021.11 日本病理学会 血栓症の発症に繋がる血栓の発生および成長機序の解明
山下 篤
Award type：Award from Japanese society, conference, symposium, etc.
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第４回ウサギバイオサイエンス研究会優秀発表賞
2016.8 ウサギバイオサイエンス研究会
山下 篤
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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日本血栓止血学会優秀ポスター賞
2010.4 日本血栓止血学会優秀ポスター賞
山下 篤
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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日本病理学会学術奨励賞
2007.3 日本病理学会
山下 篤
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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日本血栓止血学会学術奨励賞
2005.11 日本血栓止血学会
山下 篤
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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肺血栓塞栓症における非塞栓部肺動脈の変化と静脈血栓由来因子の解明
Grant number：23K06467 2023.04 - 2026.03
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）
Authorship：Principal investigator
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薬物送達システムとα線放出核種を組み合わせた革新的な白血病治療法の開発
Grant number：23H02862 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究（B）
Authorship：Coinvestigator(s)
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妊産婦死亡の主因である羊水塞栓症における血栓性病態の解明
Grant number：22K06961 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
阿萬 紫、
Authorship：Coinvestigator(s)
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静脈血栓塞栓の質的診断に繋がるDual-energyCTによる血栓の成分解析
Grant number：21K07706 2021.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
古小路 英二、
Authorship：Coinvestigator(s)
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動脈硬化性血栓症における内因系凝固因子の役割
2016.04 - 2019.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
Other research activities 【 display / non-display 】
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血栓止血用語集
2012.04 - 2015.12
血栓止血用語集の編集委員