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医学部 附属病院 病理診断科 |
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講師 |
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Expression of fibroblast activation protein-α in human deep vein thrombosis 査読あり
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 2024年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：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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Otani T., Moriguchi-Goto S., Nishihira K., Oguri N., Shibata Y., Matsuura Y., Kodama T., Asada Y., Hatakeyama K., Yamashita A.
Thrombosis Research 234 134 - 141 2024年2月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Aim: To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). Materials and methods: PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. Results: Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry–positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry–positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. Conclusions: PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects.
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Maekawa K., Nakamura E., Saito Y., Matsuura Y., Gi T., Nishihira K., Oguri N., Moriguchi-Goto S., Sato Y., Hatakeyama K., Shibata Y., Komohara Y., Kaikita K., Asada Y., Yamashita A.
PLoS ONE 20 ( 3 March ) 2025年3月
掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
Background The thrombogenic potential of cells within atherosclerotic plaques is critical in the formation of a coronary thrombus. We hypothesized that a combination of inflammatory and hypoxic stimuli enhances tissue factor (TF) expression and glycolysis in cells in atherosclerotic plaques and contributes to coronary thrombus formation. Aims To identify TF- and hexokinase (HK)-II-expressing cells in coronary atherosclerotic plaques and thrombi and determine the effects of combined inflammatory and hypoxic stimuli and glycolysis on TF expression in peripheral blood mononuclear cell-derived macrophages. Methods We immunohistochemically assessed TF and HK-II expression in stable (n = 20) and unstable (n = 24) human coronary plaques and aspirated acute coronary thrombi (n = 15). The macrophages were stimulated with tumor necrosis factor-α, interferon-γ, or interleukin-10 under normoxic (21% O2) or hypoxic (1% O2) conditions, and TF expression was assessed. Results TF and HK-II expression were increased in unstable plaques compared with stable plaques. The number of CD68- and HK-II-immunopositive cells positively correlated with the number of TF-immunopositive cells. TF- and HK-II-expressing macrophages, which expressed M1- or M2-like markers, were involved in platelet-fibrin thrombus formation in ruptured plaques. The combination of inflammatory and hypoxic conditions additively augmented TF expression and procoagulant activity in the cultured macrophages. Inhibition of glycolysis with 2-deoxyglucose reduced the augmented TF expression and procoagulant activity. Conclusion Combined inflammatory and hypoxic conditions in atherosclerotic plaques may markedly enhance procoagulant activity in macrophages and contribute to coronary thrombus formation following plaque disruption. Macrophage TF expression may be associated with glycolysis.
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Kawaguchi T., Kitamura A., Kimura M., Rikitake Y., Iwao C., Iwao K., Sumiyoshi M., Kariya Y., Matsuda M., Umekita K., Takajo I., Moriguchi-Goto S., Yamashita A., Matsumoto K., Miyazaki T.
Journal of Infection and Chemotherapy 31 ( 1 ) 2025年1月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
Treating disseminated cryptococcosis in people with human immunodeficiency virus (HIV) is challenging due to the limited availability of effective antifungals. Although isavuconazole has antifungal activity against Cryptococcus neoformans, clinical evidence is sparse because this new drug has not been approved for the treatment of cryptococcosis in the US or Europe. Here, we report a case of HIV-associated cryptococcal meningitis that relapsed during maintenance therapy with fluconazole. A Japanese man in his 20s was diagnosed with HIV-1 infection and cryptococcal meningitis. The patient was intolerant to flucytosine and was treated with liposomal amphotericin B monotherapy for 2 weeks as induction therapy, followed by fluconazole (400 mg/day) for 3 months as consolidation therapy. Four months after starting maintenance therapy with fluconazole (200 mg/day), the patient presented with fever and cough, leading to readmission to our hospital. Biopsies of a nodule in the left lung and a left cervical lymph node led to the diagnosis of disseminated cryptococcosis (pulmonary cryptococcosis and cryptococcal lymphadenitis). Although a combination of fluconazole and liposomal amphotericin B was ineffective, the patient was successfully treated with an induction therapy combining isavuconazole and liposomal amphotericin B, followed by a maintenance therapy with isavuconazole. The patient received isavuconazole orally except for loading doses, achieving stable blood concentration levels. Moreover, we observed that blood levels of amphotericin B increased gradually with repeated administration. Therefore, isavuconazole may have a potential role in the treatment of cryptococcosis, and clinical trials involving larger numbers of cases are needed to confirm its efficacy and safety.
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TBB と EBUS-TBNA における ROSE の有用性および異型細胞所見について
白濱 幸生, 野口 裕史, 徳満 貴子, 森田 勝代, 峰松 映子, 黒木 栄輝, 黒木 奈瑞菜, 齋藤 嬉和, 盛口 淸香, 佐藤 勇一郎
日本臨床細胞学会雑誌 63 ( 6 ) 285 - 294 2024年
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：公益社団法人 日本臨床細胞学会
<b>目的</b>：迅速細胞診（rapid on-site cytology evaluation：ROSE）の有用性と異型細胞の細胞所見について検討した．<b>方法</b>：経気管支生検と超音波気管支鏡ガイド下針生検に ROSE が施行され，組織診断が確定した 254 例を用いた．ROSE と細胞診最終報告（final cytology report：FCR）で，悪性疑い以上の組織診断一致率と判定別の悪性危険度を検討した．異型細胞は良性群と悪性群に分類し，背景，出現パターン，大型孤立性細胞の有無，細胞質の所見を比較した．さらに悪性群で有意差のあった壊死と大型孤立性細胞を，悪性を疑う所見として再評価した．<b>成績</b>：ROSE は FCR と比べ感度と特異度に差はなく良好だったが，悪性危険度は異型細胞で 18/28（64.3％）と高い傾向にあった．異型細胞の悪性群は壊死と大型孤立性細胞が有意に多く，化生性細胞質は良性群で有意に多かった．再評価では感度が FCR と同程度に上昇し，異型細胞の悪性危険度は 6/14（42.9％）と改善された．<b>結論</b>：ROSE の診断精度は高く，壊死と大型孤立性細胞の所見で再評価することで悪性危険度は改善し，診断精度は向上する．
DOI： 10.5795/jjscc.63.285
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An autopsy case of elderly-onset acute necrotizing encephalopathy secondary to influenza.
Ishii N, Mochizuki H, Moriguchi-Goto S, Shintaku M, Asada Y, Taniguchi A, Shiomi K, Nakazato M.
Journal of neurological sciences 2015年7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：Elsevier.
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病理学の立場からみたDICの病態
盛口清香、丸塚浩助
血栓と循環 2015年6月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア） 出版者・発行元：メディカルレビュー社
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粘液基質を伴う子宮体部平滑筋腫瘍の一例
盛口清香, 福島和子, 鮫島浩, 浅田祐士郎, 佐藤勇一郎
日本婦人科病理学会誌 5 ( 2 ) 61 - 63 2014年5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：日本婦人科病理学会
講演・口頭発表等 【 表示 ／ 非表示 】
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真性癒着胎盤の臨床病理組織学的検討
佐藤勇一郎、盛口清香、山下 篤、浅田 祐士郎、鮫島 浩
第24回日本胎盤学会学術集会
開催年月日： 2016年11月25日 - 2016年11月26日
記述言語：日本語 会議種別：ポスター発表
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神経内分泌細胞癌成分を伴った胃腺癌の1切除例
中尾大伸、河野文彰、田代耕盛、森浩貴、緒方祥吾、伊藤歌織、市成直樹、武野慎祐、池田拓人、七島篤志、中村都英、盛口淸香、佐藤勇一郎
第78回日本臨床外科学会総会
開催年月日： 2016年11月24日 - 2016年11月26日
記述言語：日本語 会議種別：ポスター発表
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眼付属器に発生した低異型度B細胞性リンパ腫の4症例
野口裕史、徳満貴子、大野招伸、峰松映子、森田勝代、黒木栄輝、盛口清香、佐藤勇一郎
第56回日本臨床細胞学会
開催年月日： 2016年11月18日 - 2016年11月19日
記述言語：日本語 会議種別：ポスター発表
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Atypical teratoid/rhabdoid tumorの2例
徳満貴子、野口裕史、大野招伸、峰松映子、森田勝代、黒木栄輝、福島剛、盛口清香、佐藤勇一郎
第55回日本臨床細胞学会
開催年月日： 2016年11月18日 - 2016年11月19日
記述言語：日本語 会議種別：ポスター発表
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Pulmonary capillary hemangiomatosis (PCH) の一生検例
前川和也、佐藤勇一郎、鮫島直樹、山下篤、盛口清香、中村恵理子、魏峻洸、鬼塚、浅田祐士郎
第107回日本病理学会総会
開催年月日： 2016年5月12日 - 2016年5月14日
記述言語：英語 会議種別：ポスター発表
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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重症熱性血小板減少症候群における血小板減少と血液凝固異常の病態解明
研究課題/領域番号：23K06425 2023年04月 - 2026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