2025/09/10 更新

写真a

ハシモト ヨシアキ
橋本 佳亮
Hashimoto Yoshiaki
所属
付属病院 小児科 助教
職名
助教
外部リンク

論文

  • Statin suppresses the development of excessive intimal proliferation in a Kawasaki disease mouse model. 国際誌

    Yusuke Motoji, Ryuji Fukazawa, Ryosuke Matsui, Makoto Watanabe, Yoshiaki Hashimoto, Noriko Nagi-Miura, Tadashi Kitamura, Kagami Miyaji

    Physiological reports   12 ( 20 )   e70096   2024年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Kawasaki disease (KD) causes vascular injury and lifelong remodeling. Excessive intimal proliferation has been observed, resulting in coronary artery lesions (CALs). However, the mechanisms underlying vascular remodeling in CAL and statin treatment have not been comprehensively elucidated. This study aimed to investigate the effects of statins on vascular remodeling using a KD mouse model. Candida albicans water-soluble substance (CAWS) was intraperitoneally injected in 5-week-old male apolipoprotein-E-deficient mice. They were categorized as follows (n = 4): control, CAWS, CAWS+statin, and late-statin groups. The mice were euthanized at 6 or 10 weeks after injection. Statins (atorvastatin) were initiated after CAWS injection, except for the late-statin group, for which statins were internally administered 6 weeks after injection. Elastica van Gieson staining and immunostaining were performed for evaluation. Statins substantially suppressed the marked neointimal hyperplasia induced by CAWS. Additionally, CAWS induced TGFβ receptor II and MAC-2 expression around the coronary arteries, which was suppressed by the statins. KD-like vasculitis might promote the formation of aneurysm by destroying elastic laminae and inducing vascular stenosis by neointimal proliferation. The anti-inflammatory effects of statins might inhibit neointimal proliferation. Therefore, statin therapy might be effective in adult patients with KD with CAL by inhibiting vascular remodeling.

    DOI: 10.14814/phy2.70096

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  • Acute focal bacterial nephritis in an infant referred with apnea caused by mixed infection with Enterococcus raffinosus and Escherichia coli.

    Yuna Kamioka, Kensuke Izumida, Eiji Ohtaka, Yoshiaki Hashimoto, Hajime Okada, Hidehiko Narazaki, Yasuhiko Itoh

    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi   2024年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 38-day-old infant was referred to our hospital for evaluation of apnea, fever, and pyuria. Invasive bacterial infection, including meningitis, was suspected because of the presence of apnea. A contrast-enhanced CT scan revealed acute localized bacterial nephritis, and meningitis was ruled out. Gram-positive cocci and Gram-negative rods, ie, Enterococcus raffinosus and Escherichia coli, were isolated from a urine culture at the referring hospital. This case report describes the youngest case of E. raffinosus infection. Apnea was the main complaint, but the origin of fever was infant acute focal bacterial nephritis (AFBN) with mixed infection. In infants, bacterial infections, especially invasive bacterial infections, can result in poor outcomes and require careful evaluation and treatment. Furthermore, the possibility of AFBN should not be overlooked, because bacteriuria or leukocyturia may be absent and can flare up if antimicrobials are not administered for an adequate duration. Although ampicillin-susceptible E. raffinosus infection in our patient responded well to treatment, there have been reports of vancomycin-resistant enterococci, which highlights the importance of proper use of antimicrobial agents to avoid producing drug-resistant bacteria.

    DOI: 10.1272/jnms.JNMS.2025_92-502

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  • Hemodynamic Evaluation of Coronary Artery Lesions after Kawasaki Disease: Comparison of Fractional Flow Reserve during Cardiac Catheterization with Myocardial Flow Reserve during 13N-Ammonia PET. 国際誌

    Makoto Watanabe, Ryuji Fukazawa, Tomonari Kiriyama, Shogo Imai, Ryosuke Matsui, Kanae Shimada, Yoshiaki Hashimoto, Koji Hashimoto, Masanori Abe, Mitsuhiro Kamisago, Yasuhiko Itoh

    Journal of cardiovascular development and disease   11 ( 8 )   2024年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial flow reserve (MFR), and myocardial blood flow volume fraction (MBF) and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 men, 1 woman) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86 ± 0.13 vs. 1.08 ± 0.09, p = 0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23 ± 0.23 vs. 1.88 ± 0.29, p = 0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

    DOI: 10.3390/jcdd11080229

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  • Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction.

    Ryosuke Matsui, Ryuji Fukazawa, Ryohei Fukunaga, Yusuke Motoji, Yoshiaki Hashimoto, Makoto Watanabe, Noriko Nagi-Miura, Yasuhiko Itoh

    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi   91 ( 3 )   285 - 295   2024年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFβ receptors. Measurement of the inflammatory cytokines IL-1β, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

    DOI: 10.1272/jnms.JNMS.2024_91-307

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  • Three cases of young children who underwent effective catheter treatment for severe coronary stenosis caused by Kawasaki disease.

    Makoto Watanabe, Ryuji Fukazawa, Ryousuke Matsui, Kanae Shimada, Yoshiaki Hashimoto, Koji Hashimoto, Masanori Abe, Mitsuhiro Kamisago

    Journal of cardiology cases   27 ( 4 )   180 - 183   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    UNLABELLED: Three patients, aged 2 years 0 months, 2 years 2 months, and 6 years 1 month at the time of plain old balloon angioplasty (POBA), developed an aneurysm in the left anterior descending coronary branch after suffering from Kawasaki disease. POBA was subsequently performed due to 99 % stenosis proximal to the aneurysm. There was no restenosis within a few years after percutaneous coronary intervention, and there was no evidence of ischemia, although 75 % restenosis occurred in two patients after 7 years.Although calcified lesions are more likely to occur 6 years after the onset of Kawasaki disease, none of the patients in this study had calcified lesions within 4 years of Kawasaki disease onset, and good results were obtained with POBA alone. POBA can be safely performed in children and is an effective treatment for improving myocardial ischemia if calcification has not progressed. LEARNING OBJECTIVE: Plain old balloon angioplasty (POBA) can be performed effectively and safely for Kawasaki disease coronary artery stenosis in early childhood if calcification is minimal, with little restenosis for at least several years. POBA is a useful tool in the treatment of coronary artery stenosis in early childhood.

    DOI: 10.1016/j.jccase.2023.01.001

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  • Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model. 国際誌

    Yusuke Motoji, Ryuji Fukazawa, Ryosuke Matsui, Yoshinori Abe, Ikuno Uehara, Makoto Watanabe, Yoshiaki Hashimoto, Yasuo Miyagi, Noriko Nagi-Miura, Nobuyuki Tanaka, Yosuke Ishii

    International journal of molecular sciences   23 ( 24 )   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE-) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.

    DOI: 10.3390/ijms232416108

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  • Virtual histology intravascular ultrasound evaluation of coronary artery lesions within 1 year and more than 10 years after the onset of Kawasaki disease. 国際誌

    Makoto Watanabe, Ryuji Fukazawa, Shunichi Ogawa, Takashi Ohkubo, Masanori Abe, Koji Hashimoto, Yoshiaki Hashimoto, Yasuhiko Itoh

    Journal of cardiology   75 ( 2 )   171 - 176   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Coronary artery evaluation by virtual histological intravascular ultrasonography (VH-IVUS) late in Kawasaki disease (KD) shows intimal thickening, calcification, fatty components, and necrosis of regressed coronary artery lesions (CALs). However, it is not clear when these VH-IVUS findings start to occur. Therefore, we evaluated coronary arteries using VH-IVUS in patients with early-stage KD and tried to determine whether these atherosclerotic findings on VH-IVUS were different from that in patients with late-stage KD. METHODS: Eighteen patients with KD aged between 1 and 32 years who had CALs and underwent cardiac catheterization between January 1, 2008 and December 31, 2014 were included. They were divided into 2 groups-those with the disease for <1 year (group A) and those with it for >10 years (group B). VH-IVUS findings were compared between the groups. The coronary arteries were divided based on coronary angiography findings into normal, regressed (dilated CALs regressed to a normal size), and aneurysmal lesions. The Wilcoxon signed-rank test was used in the statistical analysis. RESULTS: In both regressed and aneurysmal lesions, marked intimal proliferation and atherosclerotic findings (fibro-fatty and necrotic core lesions) were observed. In addition, there was no difference in the area percentage of atherosclerosis between the groups. CONCLUSIONS: VH-IVUS revealed that atherosclerotic-like findings exist in CALs in patients with KD, even within a year of onset. The findings were almost the same in those with the disease for >10 years. Because there is no histological evidence of atherosclerosis in KD, these VH-IVUS findings may indicate complex histological findings of KD. Nevertheless, early interventions to help reduce the risk factors of atherosclerosis may be required in these patients.

    DOI: 10.1016/j.jjcc.2019.06.015

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  • Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease.

    Yoshiaki Hashimoto, Ryuji Fukazawa, Noriko Nagi-Miura, Naohito Ohno, Nobuko Suzuki, Yasuhiro Katsube, Mitsuhiro Kamisago, Miharu Akao, Makoto Watanabe, Koji Hashimoto, Kanae Tsuno, Ryosuke Matsui, Yasuhiko Itoh

    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi   86 ( 2 )   108 - 116   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Kawasaki disease (KD), a systemic vasculitis, is suspected to be related to abnormalities in innate immunity. Based on the important role of IL-1 signaling in innate immunity, we investigated the effects of an anti-IL-1β antibody using a Candida albicans water-soluble fraction (CAWS)-induced mouse model of KD. METHODS: CAWS (0.5 mg/mouse) was injected intraperitoneally into 5-week-old DBA/2 mice on five consecutive days. An anti-Murine IL-1β antibody (01BSUR) was administered at various doses (2.5, 5.0, and 10.0 mg/kg) and time points (2 days before, same day, and 2, 5, 7, and 14 days after CAWS administration). After 4 weeks, vasculitis in the aortic root was investigated histologically. Cytokines including IL-1β, -6, -10, and TNF-α were also measured. RESULTS: Groups administered 01BSUR at all doses showed a significant reduction in the area of vasculitis. In addition, 01BSUR inhibited vasculitis until 7 days after CAWS administration. In the analysis of various time points, the level of IL-6 was lower in all groups compared to the CAWS only group, but the levels of IL-1β, TNFα, and IL-10 were lower when 01BSUR was administered before CAWS. On the other hand, TNFα and IL-10 levels were restored when 01BSUR was administered after CAWS, suggesting that 01BSUR may have additional effects beyond blocking IL-1β signaling. CONCLUSIONS: The anti-IL-1β antibody significantly attenuated CAWS-induced vasculitis. The mechanism of inhibiting vasculitis is thought to include inhibition of the IL-1β pathway and additional effects beyond blocking IL-1β signaling.

    DOI: 10.1272/jnms.JNMS.2019_86-206

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