Faculty Profiles - UCHIDA Haruhito

Papers - UCHIDA Haruhito

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2型糖尿病患者における血中GPIHBP1濃度の臨床的意義

黒岡直子, 江口潤, 内田治仁, 村上和敏, 亀井信二, 菊辻徹, 佐々木佐起子, 関明穂, 和田淳

日本動脈硬化学会総会プログラム・抄録集 53回 228 - 228 2021.10

尿中クレアチニン(Cr)排泄量低下が健康関連QOLに与える影響についての検討

大西康博, 内田治仁, 杉山斉, 浅野健一郎, 徳増裕宣, 和田淳

日本老年医学会雑誌 58 ( 4 ) 657 - 657 2021.10

Total vascular resistance, augmentation index, and augmentation pressure increase in patients with peripheral artery disease. International journal

Rika Takemoto, Haruhito A Uchida, Hironobu Toda, Ken Okada, Fumio Otsuka, Hiroshi Ito, Jun Wada

Medicine 100 ( 32 ) e26931 2021.8

Language：English Publishing type：Research paper (scientific journal)

ABSTRACT: Peripheral arterial disease (PAD) is one of major vascular diseases which frequently coexists with coronary arterial disease and cerebrovascular disease. The patients with PAD have a poor prognosis when it progresses. A new blood pressure testing device enables to simultaneously measure brachial blood pressure (BP), central BP, and several vascular parameters, with easy and non-invasive, in a short time. Here, we aimed to evaluate these arterial stiffness parameters in patients with PAD.In this study, 243 consecutive patients who were suspected of having PAD and referred to our hospital from September 2016 to June 2019, were registered. Several parameters, such as brachial BP, central BP, aortic pulse wave velocity (aPWV), total vascular resistance (TVR), augmentation index (AI) and augmentation pressure (AP), were determined by Mobil-O-Graph. Ankle-brachial pressure index (ABI) was used to define PAD (ABI ≤ 0.9 as PAD). The relationship between PAD and central BP, aPWV, TVR, AI, or AP were investigated.One hundred sixty-two patients (67%) were categorized as the PAD group and 81 patients (33%) as the non-PAD group. In the PAD group, the systolic brachial BP and central systolic BP were significantly higher than those in the non-PAD group (138 ± 24 mmHg vs 131 ± 19 mmHg, P < .05, 125 ± 22 mmHg vs 119 ± 18 mmHg, P < .05, respectively). TVR, AI, and AP were significantly higher in the PAD group (1785 ± 379 dyn s/cm5 vs 1661 ± 317 dyn s/cm5, P < .05, 26.2 ± 13.0% vs 22.2 ± 13.3%, P < .05, 13.5 ± 9.4 mmHg vs 10.7 ± 7.2 mmHg, P < .05, respectively). No significant differences in diastolic BP, central diastolic BP, and aPWV were found between the groups. Multivariate logistic regression analysis revealed that PAD was significantly associated with TVR, AI, and AP (P < .05, respectively).TVR/AP/AI were significantly higher in the PAD group than in the non-PAD group.

DOI： 10.1097/MD.0000000000026931

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Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study. International journal

Mariko Tsuchida-Nishiwaki, Haruhito A Uchida, Hidemi Takeuchi, Noriyuki Nishiwaki, Yohei Maeshima, Chie Saito, Hitoshi Sugiyama, Jun Wada, Ichiei Narita, Tsuyoshi Watanabe, Seiichi Matsuo, Hirofumi Makino, Akira Hishida, Kunihiro Yamagata

Scientific reports 11 ( 1 ) 14990 - 14990 2021.7

Language：English Publishing type：Research paper (scientific journal)

It is well-known that hypertension exacerbates chronic kidney disease (CKD) progression, however, the optimal target blood pressure (BP) level in patients with CKD remains unclear. This study aimed to assess the optimal BP level for preventing CKD progression. The risk of renal outcome among different BP categories at baseline as well as 1 year after, were evaluated using individual CKD patient data aged between 40 and 74 years from FROM-J [Frontier of Renal Outcome Modifications in Japan] study. The renal outcome was defined as ≥ 40% reduction in estimated glomerular filtration rate to < 60 mL/min/1.73 m2, or a diagnosis of end stage renal disease. Regarding baseline BP, the group of systolic BP (SBP) 120-129 mmHg had the lowest risk of the renal outcome, which increased more than 60% in SBP ≥ 130 mmHg group. A significant increase in the renal outcome was found only in the group of diastolic BP ≥ 90 mmHg. The group of BP < 130/80 mmHg had a benefit for lowering the risk regardless of the presence of proteinuria, and it significantly reduced the risk in patients with proteinuria. Achieving SBP level < 130 mmHg after one year resulted in a 42% risk reduction in patients with SBP level ≥ 130 mmHg at baseline. Targeting SBP level < 130 mmHg would be associated with the preferable renal outcome.Clinical Trial Registration-URL: https://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000001159 (16/05/2008).

DOI： 10.1038/s41598-021-94467-z

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透析患者におけるCVDとフレイルの関係

竹内英実, 内田治仁, 大高望, 奥山由加, 梅林亮子, 杉山斉, 和田淳

日本腎臓学会誌 63 ( 4 ) 431 - 431 2021.6

慢性腎臓病における貧血管理 Kakusyo 3C Studyからの検討

奥山由加, 内田治仁, 大高望, 竹内英実, 辻憲二, 田邊克幸, 木野村賢, 吉田賢司, 前島洋平, 杉山斉, 伊藤浩, 和田淳

日本腎臓学会誌 63 ( 4 ) 474 - 474 2021.6

中四国地域におけるCKDおよびCVDの関連に関するコホート研究 Kakusyo 3C Studyのイベント解析

大高望, 内田治仁, 竹内英実, 辻憲二, 田邊克幸, 木野村賢, 吉田賢司, 前島洋平, 杉山斉, 伊藤浩, 和田淳

日本腎臓学会誌 63 ( 4 ) 464 - 464 2021.6

岡山市CKDネットワーク(OCKD-NET)におけるCKD病診連携10年後の追跡調査

大西康博, 内田治仁, 大高望, 竹内英実, 辻憲二, 田邊克幸, 森永裕士, 木野村賢, 喜多村真治, 前島洋平, 杉山斉, 太田康介, 丸山啓輔, 大城義之, 森岡茂, 瀧上慶一, 蒲生直幸, 和田淳

日本腎臓学会誌 63 ( 4 ) 513 - 513 2021.6

甲状腺機能低下症とCKDの関連性におけるCr代謝の影響についての検討

内山奈津実, 辻憲二, 喜多村真治, 稲垣兼一, 内田治仁, 杉山斉, 和田淳

日本腎臓学会誌 63 ( 4 ) 463 - 463 2021.6

両側乳頭浮腫を伴う肥厚性硬膜炎を発症した維持血液透析患者の一例

内山奈津実, 木野村賢, 高橋謙作, 谷村智史, 森岡朋代, 加納弓月, 川北智英子, 田邊克幸, 内田治仁, 杉山斉, 難波清人, 和田淳

中国腎不全研究会誌 29 27 - 28 2021.6

岡山市CKDネットワーク(OCKD-NET)におけるCKD病診連携10年後の追跡調査

日本腎臓学会誌 63 ( 4 ) 513 - 513 2021.6

甲状腺機能低下症とCKDの関連性におけるCr代謝の影響についての検討

内山奈津実, 辻憲二, 喜多村真治, 稲垣兼一, 内田治仁, 杉山斉, 和田淳

日本腎臓学会誌 63 ( 4 ) 463 - 463 2021.6

中四国地域におけるCKDおよびCVDの関連に関するコホート研究 Kakusyo 3C Studyのイベント解析

大高望, 内田治仁, 竹内英実, 辻憲二, 田邊克幸, 木野村賢, 吉田賢司, 前島洋平, 杉山斉, 伊藤浩, 和田淳

日本腎臓学会誌 63 ( 4 ) 464 - 464 2021.6

慢性腎臓病における貧血管理 Kakusyo 3C Studyからの検討

奥山由加, 内田治仁, 大高望, 竹内英実, 辻憲二, 田邊克幸, 木野村賢, 吉田賢司, 前島洋平, 杉山斉, 伊藤浩, 和田淳

日本腎臓学会誌 63 ( 4 ) 474 - 474 2021.6

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2) International journal

Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Satoshi Miyamoto, Haruhito A. Uchida, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhiro Miyashita, Shinichiro Ando, Tomokazu Nunoue, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

Frontiers in Cardiovascular Medicine 8 668059 - 668059 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

<bold>Background:</bold> Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.

<bold>Methods:</bold> Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.

<bold>Results:</bold> During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, <italic>P</italic> = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, <italic>P</italic> = 0.001). Common glycan binding to these lectins was high-mannose type of <italic>N</italic>-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, <italic>P</italic> = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, <italic>P</italic> = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].

<bold>Conclusion:</bold> The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal <italic>N</italic>-glycosylation occurring in patients with diabetes at higher risk of CVE.

<bold>Trial Registration:</bold> This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: <ext-link>https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482</ext-link>).

DOI： 10.3389/fcvm.2021.668059

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Vasohibin-2 Aggravates Development of Ascending Aortic Aneurysms but not Abdominal Aortic Aneurysms nor Atherosclerosis in ApoE-Deficient Mice. International journal

Nozomu Otaka, Haruhito A Uchida, Michihiro Okuyama, Yoshiko Hada, Yasuhiro Onishi, Yuki Kakio, Hidemi Takeuchi, Ryoko Umebayashi, Katsuyuki Tanabe, Venkateswaran Subramanian, Alan Daugherty, Yasufumi Sato, Jun Wada

American journal of hypertension 34 ( 5 ) 467 - 475 2021.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Vasohibin-2 (VASH2) has been isolated as a homologue of vasohibin-1 (VASH1) that promote angiogenesis counteracting with VASH1. Chronic angiotensin II (AngII) infusion promotes both ascending and abdominal aortic aneurysms (AAs) in mice. The present study aimed to investigate whether exogenous VASH2 influenced AngII-induced vascular pathology in apolipoprotein E deficient (ApoE -/-) mice. METHODS: Male, ApoE -/- mice (9 to 14 weeks old) were injected with Ad LacZ or Ad VASH2. After a week, saline or AngII (1,000 ng/kg/min) was infused into the mice subcutaneously via mini-osmotic pumps for 3 weeks. Consequently, all these mice were divided into 4 groups: saline + LacZ (n=5), saline + VASH2 (n=5), AngII + LacZ (n=18), and AngII + VASH2 (n=17). RESULTS: Exogenous VASH2 had no significant effect on ex vivo maximal diameters of abdominal aortas (AngII + LacZ; 1.67±0.17 mm, AngII + VASH2; 1.52±0.16 mm, n.s.) or elastin fragmentation and accumulation of inflammatory cells. Conversely, exogenous VASH2 significantly increased intima areas of aortic arches (AngII + LacZ; 16.6±0.27 mm 2, AngII + VASH2; 18.6±0.64 mm 2, p=0.006). VASH2 effect of AngII-induced ascending AAs was associated with increased cleaved caspase-3 abundance. AngII-induced atherosclerosis was not altered by VASH2. CONCLUSION: The present study demonstrated that augmented VASH2 expression had no effect of AngII-induced abdominal AAs or atherosclerosis, while increasing dilation in the ascending aorta.

DOI： 10.1093/ajh/hpaa181

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Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice. International journal

Latha Muniappan, Michihiro Okuyama, Aida Javidan, Devi Thiagarajan, Weihua Jiang, Jessica J Moorleghen, Lihua Yang, Anju Balakrishnan, Deborah A Howatt, Haruhito A Uchida, Takaomi C Saido, Venkateswaran Subramanian

Arteriosclerosis, thrombosis, and vascular biology 41 ( 5 ) 1694 - 1709 2021.5

妊娠中に加温式リサキュレーション法を施行した家族性高コレステロール血症(ホモ接合体)の1例

奥山由加, 内田治仁, 高橋謙作, 藤原千尋, 竹内英実, 田邊克幸, 木野村賢, 和田淳

日本透析医学会雑誌 54 ( Suppl.1 ) 360 - 360 2021.5

Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Macrophage. International journal

Yoshiko Hada, Haruhito A Uchida, Jun Wada

BioMed research international 2021 5570885 - 5570885 2021

Language：English Publishing type：Research paper (scientific journal)

Several studies have reported the efficacy and safety of polyphenols in human health; however, the verification of their efficacy remains insufficient. The aim of this study was to examine whether fisetin, one of flavonoids prevalently present in fruits and vegetables, could suppress lipopolysaccharide- (LPS-) induced inflammatory responses in macrophages. LPS increased proinflammatory mRNA abundance (MCP 1, IL-1β, and iNOS) but were suppressed by fisetin. The increment of nitric oxide by LPS, an oxidative stress factor, was attenuated by fisetin. In addition, LPS-enhanced phosphorylation of mitogen-activated protein kinase (ERK and JNK) was reduced. Finally, fisetin attenuated the expression or activity of uPA, uPAR, MMP-2, and MMP-9, which are known as associated factors of macrophage recruitment or infiltration. In conclusion, fisetin is a promising therapeutic agent for macrophage-related inflammation diseases, like sepsis and atherosclerosis.

DOI： 10.1155/2021/5570885

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Inhibition of Interleukin-6 Signaling Attenuates Aortitis, Left Ventricular Hypertrophy and Arthritis in Interleukin-1 Receptor Antagonist Deficient Mice. Reviewed International journal

Yoshiko Hada, Haruhito A Uchida, Tomoyuki Mukai, Fumiaki Kojima, Masashi Yoshida, Hidemi Takeuchi, Yuki Kakio, Nozomu Otaka, Yoshitaka Morita, Jun Wada

Clinical science (London, England : 1979) 134 ( 20 ) 2771 - 2787 2020.10

Language：English Publishing type：Research paper (scientific journal)

The aim of this study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into 4 groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight % of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis.

DOI： 10.1042/CS20201036

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