2025/07/23 更新

写真a

ワダ ジュン
和田 淳
WADA Jun
所属
医歯薬学域 教授
職名
教授
外部リンク

学位

  • 医学博士

研究キーワード

  • 腎臓病学

  • Nephrology

  • 糖尿病

  • Diabetes Mellitus

研究分野

  • ライフサイエンス / 腎臓内科学

  • ライフサイエンス / 代謝、内分泌学

学歴

  • 岡山大学    

    - 1992年

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    国名: 日本国

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  • 岡山大学   Medical School  

    - 1988年

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    国名: 日本国

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経歴

  • 岡山大学   腎/免疫・内分泌代謝内科学   教授

    2015年8月 - 現在

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  • 岡山大学   腎・免疫・内分泌代謝内科学   准教授

    2010年1月 - 2015年7月

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  • 文部科学省研究振興局   学術調査官

    2006年8月 - 2008年7月

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  • Northwestern University Medical School   Research Associate

    1992年10月 - 1996年11月

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    国名:アメリカ合衆国

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所属学協会

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委員歴

  • 日本腎臓リハビリテーション学会   理事  

    2023年5月 - 現在   

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    団体区分:学協会

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  • 日本肥満学会   理事  

    2021年10月 - 現在   

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  • 日本腎臓学会   理事  

    2020年4月 - 現在   

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  • 日本糖尿病合併症学会   評議員  

    2017年10月 - 現在   

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  • 日本動脈硬化学会   評議員  

    2017年6月 - 現在   

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  • 膵臓移植地域適応検討委員会   委員  

    2016年5月 - 現在   

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    団体区分:学協会

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  • 日本内科学会   評議員  

    2016年4月 - 現在   

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    団体区分:学協会

    日本内科学会

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  • 日本糖尿病・肥満動物学会   評議員  

    2015年3月 - 現在   

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  • 日本腎臓学会   評議員  

    2013年1月 - 現在   

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    団体区分:学協会

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  • 日本病態栄養学会   学術評議員  

    2011年4月 - 現在   

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    団体区分:学協会

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  • 日本肥満学会   評議員  

    2007年10月 - 現在   

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    団体区分:学協会

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  • 日本糖尿病学会   評議員  

    2004年 - 現在   

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    団体区分:学協会

    日本糖尿病学会

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論文

  • Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells

    Yoshihiko Itoh, Kenichi Inagaki, Tomohiro Terasaka, Eisaku Morimoto, Takahiro Ishii, Kimitomo Yamaoka, Satoshi Fujisawa, Jun Wada

    International Journal of Molecular Sciences   2025年7月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms26146927

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  • Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes

    Naoko Nishii, Tomoko Kawai, Hiroki Yasuoka, Tadashi Abe, Nanami Tatsumi, Yuika Harada, Takaaki Miyaji, Shunai Li, Moemi Tsukano, Masami Watanabe, Daisuke Ogawa, Jun Wada, Kohji Takei, Hiroshi Yamada

    International Journal of Molecular Sciences   2025年3月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms26062485

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  • Supplement-induced acute kidney injury reproduced in kidney organoids

    Hiroyuki Nakanoh, Kenji Tsuji, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada

    American Journal of Nephrology   2025年2月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000544795

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  • Noncoding RNAs and diabetic kidney disease 査読

    Jun Wada

    Journal of Diabetes Investigation   2025年1月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/jdi.14331

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  • The Gut–Kidney Axis in Chronic Kidney Diseases

    Kenji Tsuji, Naruhiko Uchida, Hiroyuki Nakanoh, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada

    Diagnostics   2024年12月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/diagnostics15010021

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  • Characteristics of diabetes mellitus patients with nonviral chronic liver disease who developed hepatocellular carcinoma. 査読 国際誌

    Kyo Sasaki, Miwa Kawanaka, Yasuyuki Tomiyama, Akinobu Takaki, Motoyuki Otsuka, Fusao Ikeda, Naoko Yoshioka, Hideaki Kaneto, Jun Wada, Tetsuya Fukuda, Keisuke Hino, Sohji Nishina

    Hepatology research : the official journal of the Japan Society of Hepatology   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)  

    AIM: Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease. METHOD: Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. The clinical and laboratory parameters of patients with and without HCC were compared. RESULTS: Age ≥65 years, alcohol intake, lack of hepatic steatosis, triglyceride level <111 mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5 ng/mL, and des-γ-carboxy prothrombin concentration ≥26 mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p < 0.001) was associated with HCC development in patients aged <65 years, and medication for diabetes mellitus (OR 5.72, p = 0.001), lack of hepatic steatosis (OR 4.47, p = 0.002), lactate dehydrogenase ≥198 IU/L (OR 2.751, p = 0.031), M2BPGi ≥1.18 COI (OR 9.05, p < 0.001), and FIB-4 index ≥2.59 (OR 3.22, p = 0.017) were associated with HCC development in patients aged ≥65 years. CONCLUSIONS: In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging.

    DOI: 10.1111/hepr.14124

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  • A case of renal hypouricemia due to T217M mutation in SLC22A12 incidentally associated with IgA nephropathy. 査読 国際誌

    Yoshimasa Sakurabu, Haruhito A Uchida, Toshihisa Tahara, Tomohiko Asakawa, Haruka Yamasaki, Katsuyoshi Katayama, Shugo Okamoto, Yasuhiro Onishi, Natsumi Matsuoka-Uchiyama, Keiko Tanaka, Hidemi Takeuchi, Kenji Tsuji, Ryoko Umebayashi, Yuki Ohashi, Kimiyoshi Ichida, Jun Wada

    Clinical case reports   12 ( 9 )   e9368   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events.

    DOI: 10.1002/ccr3.9368

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  • Guidelines for clinical evaluation of chronic kidney disease in early stages : AMED research on regulatory science of pharmaceuticals and medical devices. 査読

    Yuka Sugawara, Eiichiro Kanda, Takayuki Hamano, Seiji Itano, Hirokazu Okada, Koji Tomori, Yusuke Watanabe, Wataru Asakura, Yoshitaka Isaka, Kunitoshi Iseki, Tomoko Usui, Yusuke Suzuki, Mototsugu Tanaka, Rimei Nishimura, Kei Fukami, Kunihiro Matsushita, Jun Wada, Hirotaka Watada, Kohjiro Ueki, Naoki Kashihara, Masaomi Nangaku

    Clinical and experimental nephrology   28 ( 9 )   847 - 865   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients. METHODS: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal. RESULTS: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review. CONCLUSION: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

    DOI: 10.1007/s10157-024-02514-6

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  • Factors influencing the efficacy and safety of esaxerenone in hypertensive patients: a pooled analysis of five clinical studies on different comorbidities. 査読 国際誌

    Kazuomi Kario, Tomohiro Katsuya, Jun Wada, Hirohiko Motoki, Koichiro Kuwahara, Kenichi Tsujita, Takashi Taguchi, Ayumi Tanabe, Tatsuo Shimosawa

    Hypertension research : official journal of the Japanese Society of Hypertension   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)  

    This study aimed to identify factors associated with a strong home blood pressure (BP)-lowering effect of esaxerenone and the incidence of elevated serum potassium levels in hypertensive patients treated with esaxerenone. A pooled analysis of five multicenter, prospective, open-label single-arm studies was conducted, including 479 patients in the full analysis set (FAS) and 492 patients in the safety analysis set. Multivariate linear regression analysis of morning home systolic BP (SBP) and diastolic BP (DBP) changes from baseline to Week 12 in the FAS (primary endpoint) showed that male sex (estimated change 4.37 mmHg), office pulse rate ≥100 beats/min (25.10 mmHg), and calcium channel blocker (CCB) use as a basal antihypertensive agent (4.53 mmHg) were significantly associated with a positive estimated change (weaker BP-lowering effect) in morning home SBP. CCB use (3.70 mmHg) was associated with a positive estimated change in morning home DBP. Urine albumin-to-creatinine ratio 30 to <300 mg/gCr (-4.13 mmHg) was significantly associated with a negative estimated change (stronger BP-lowering effect) in morning home SBP. Based on multivariate logistic regression analysis, elevated baseline serum potassium level (≥4.5 vs < 4.5 mEq/L, odds ratio 13.502) was significantly associated with a high incidence of serum potassium level ≥5.5 mEq/L after esaxerenone treatment. In conclusion, factors associated with a strong BP-lowering effect of esaxerenone were female sex and use of renin-angiotensin system inhibitors as a basal antihypertensive drug. Patients with baseline serum potassium levels ≥4.5 mEq/L had an increased risk of developing elevated serum potassium levels (≥5.5 mEq/L) after esaxerenone treatment.

    DOI: 10.1038/s41440-024-01818-0

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  • Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease. 査読

    Seiji Kishi, Takaya Nakashima, Tadahiro Goto, Hajime Nagasu, Craig R Brooks, Hirokazu Okada, Kouichi Tamura, Toshiaki Nakano, Ichiei Narita, Shoichi Maruyama, Yuichiro Yano, Takashi Yokoo, Takashi Wada, Jun Wada, Masaomi Nangaku, Naoki Kashihara

    Clinical and experimental nephrology   28 ( 8 )   784 - 792   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)  

    BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex (J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

    DOI: 10.1007/s10157-024-02486-7

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  • A case of membranous nephropathy complicated by Cronkhite-Canada syndrome successfully treated with mizoribine. 査読

    Hiroyuki Nakanoh, Kenji Tsuji, Shiho Morimoto, Kazuhiko Fukushima, Masaya Iwamuro, Haruhito A Uchida, Jun Wada

    CEN case reports   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)  

    Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS.

    DOI: 10.1007/s13730-024-00908-9

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  • Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database. 査読 国際誌

    Tomohiko Kanaoka, Hiromichi Wakui, Yuichiro Yano, Hajime Nagasu, Hiroshi Kanegae, Masaomi Nangaku, Yosuke Hirakawa, Naoki Nakagawa, Jun Wada, Kazuhiko Tsuruya, Toshiaki Nakano, Shoichi Maruyama, Takashi Wada, Masaaki Konishi, Takanori Nagahiro, Kunihiro Yamagata, Ichiei Narita, Motoko Yanagita, Yoshio Terada, Shinichi Araki, Masanori Emoto, Hirokazu Okada, Yoshitaka Isaka, Yusuke Suzuki, Takashi Yokoo, Hiromi Kataoka, Eiichiro Kanda, Naoki Kashihara, Kouichi Tamura

    Diabetes, obesity & metabolism   26 ( 7 )   2905 - 2914   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)  

    AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = -0.609, p = .039; β = -2.298, p < .001; β = -0.936, p = .048; β = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

    DOI: 10.1111/dom.15611

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  • Preventive effects of vasohibin-2-targeting peptide vaccine for diabetic nephropathy. 査読 国際誌

    Yuri Nakashima, Katsuyuki Tanabe, Tomoyo Mifune, Takato Nakadoi, Hiroki Hayashi, Hironori Nakagami, Yasufumi Sato, Jun Wada

    American journal of physiology. Renal physiology   326 ( 6 )   F1054-F1065   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 wk apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 wk after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db/db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation.NEW & NOTEWORTHY This study demonstrated preventive effects of VASH2-targeting peptide vaccine therapy on albuminuria and glomerular microinflammation in STZ-induced diabetic mouse model by inhibiting renal Angpt2 expression. The vaccination was also effective in db/db mice. The results highlight the importance of VASH2 in the pathogenesis of early-stage diabetic nephropathy and the practicability of anti-VASH2 strategy as a vaccine therapy.

    DOI: 10.1152/ajprenal.00341.2023

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  • Effects of empagliflozin in patients with chronic kidney disease from Japan: exploratory analyses from EMPA-KIDNEY. 査読

    Masaomi Nangaku, William G Herrington, Shinya Goto, Shoichi Maruyama, Naoki Kashihara, Kohjiro Ueki, Jun Wada, Hirotaka Watada, Eitaro Nakashima, Ryonfa Lee, Dan Massey, Kaitlin J Mayne, Aiko Tomita, Richard Haynes, Sibylle J Hauske, Takashi Kadowaki

    Clinical and experimental nephrology   28 ( 6 )   588 - 595   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: EMPA-KIDNEY assessed the effects of empagliflozin 10 mg once daily vs. placebo in 6609 patients with chronic kidney disease (CKD) at risk of progression, including 612 participants from Japan. METHODS: Eligibility required an estimated glomerular filtration rate (eGFR) of ≥ 20 < 45; or ≥ 45 < 90 ml/min/1.73m2 with a urinary albumin-to-creatinine ratio (uACR) of ≥ 200 mg/g. The primary outcome was a composite of kidney disease progression (end-stage kidney disease, a sustained eGFR decline to < 10 ml/min/1.73m2 or ≥ 40% from randomization, or renal death) or cardiovascular death. In post-hoc analyses, we explored the effects of empagliflozin in participants from Japan vs. non-Japan regions, including additional models assessing whether differences in treatment effects between these regions could result from differences in baseline characteristics. RESULTS: Japanese participants had higher levels of albuminuria and eGFR than those from non-Japan regions. During a median of 2.0 year follow-up, a primary outcome occurred in 432 patients (13.1%) in the empagliflozin group and in 558 patients (16.9%) in the placebo group (hazard ratio [HR], 0.72, 95% confidence interval [95%CI] 0.64-0.82; P < 0.0001). Among the participants from non-Japan regions, there were 399 vs. 494 primary outcomes (0.75, 0.66-0.86), and 33 vs. 64 (0.49, 0.32-0.75; heterogeneity p = 0.06) in Japan. Results were similar when models explicitly considered treatment interactions with diabetes status, categories of eGFR/uACR, and recruitment in Japan (heterogeneity p = 0.08). Safety outcomes were broadly comparable between the two groups, and by Japanese status. CONCLUSIONS: Empagliflozin safely reduced the risk of "kidney disease progression or cardiovascular death" in patients with CKD, with consistent effects in participants from Japan.

    DOI: 10.1007/s10157-024-02489-4

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  • Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3). 査読 国際誌

    Asami Ueno, Yasuhiro Onishi, Koki Mise, Satoshi Yamaguchi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Haruhito A Uchida, Kenichi Shikata, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, Tomokazu Nunoue, Jun Wada

    BMJ open diabetes research & care   12 ( 3 )   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. RESEARCH DESIGN AND METHODS: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. RESULTS: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. CONCLUSIONS: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD. TRIAL REGISTRATION NUMBER: UMIN000011525.

    DOI: 10.1136/bmjdrc-2024-004237

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  • All three in one: it's a cohort, proteomics, and Mendelian randomization biomarker study. 査読 国際誌

    Jun Wada

    The Journal of clinical endocrinology and metabolism   2024年5月

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    記述言語:英語  

    DOI: 10.1210/clinem/dgae359

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  • Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes. 査読 国際誌

    Zannatun Nyma, Kaori Kitaoka, Yuichiro Yano, Hiroshi Kanegae, Nomin Bayaraa, Seiji Kishi, Hajime Nagasu, Toshiaki Nakano, Jun Wada, Shoichi Maruyama, Naoki Nakagawa, Kouichi Tamura, Takashi Yokoo, Motoko Yanagita, Ichiei Narita, Kunihiro Yamagata, Takashi Wada, Kazuhiko Tsuruya, Naoki Nakashima, Yoshitaka Isaka, Masaomi Nangaku, Naoki Kashihara, Hirokazu Okada

    Scientific reports   14 ( 1 )   11481 - 11481   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0-5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.

    DOI: 10.1038/s41598-024-62152-6

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  • A multicenter, open‐label, single‐arm trial of the long‐term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE‐02) 査読

    Yushi Hirota, Yasumasa Kakei, Junta Imai, Hideki Katagiri, Ken Ebihara, Jun Wada, Junichi Suzuki, Tatsuhiko Urakami, Takashi Omori, Wataru Ogawa

    Journal of Diabetes Investigation   15 ( 9 )   1211 - 1219   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS/INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment-refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single-arm trial (EMPIRE-01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE-02) that followed on from EMPIRE-01. MATERIALS AND METHODS: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE-01 trial participated in EMPIRE-02. RESULTS: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE-02. The improvement in mean values of glycemic parameters observed in EMPIRE-01 was not sustained in EMPIRE-02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE-02 after exclusion of this subject from analysis. CONCLUSIONS: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

    DOI: 10.1111/jdi.14226

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  • GRP78 Contributes to the Beneficial Effects of SGLT2 Inhibitor on Proximal Tubular Cells in DKD 査読 国際誌

    Atsuko Nakatsuka, Satoshi Yamaguchi, Jun Wada

    Diabetes   73 ( 5 )   763 - 779   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on kidney function are well-known; however, their molecular mechanisms are not fully understood. We focused on 78-kDa glucose-regulated protein (GRP78) and its interaction with SGLT2 and integrin-β1 beyond the chaperone property of GRP78. In streptozotocin (STZ)-induced diabetic mouse kidneys, GRP78, SGLT2, and integrin-β1 increased in the plasma membrane fraction, while they were suppressed by canagliflozin. The altered subcellular localization of GRP78/integrin-β1 in STZ mice promoted epithelial mesenchymal transition (EMT) and fibrosis, which were mitigated by canagliflozin. High-glucose conditions reduced intracellular GRP78, increased its secretion, and caused EMT-like changes in cultured HK2 cells, which were again inhibited by canagliflozin. Urinary GRP78 increased in STZ mice, and in vitro experiments with recombinant GRP78 suggested that inflammation spread to surrounding tubular cells and that canagliflozin reversed this effect. Under normal glucose culture, canagliflozin maintained sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) activity, promoted ER robustness, reduced ER stress response impairment, and protected proximal tubular cells. In conclusion, canagliflozin restored subcellular localization of GRP78, SGLT2, and integrin-β1 and inhibited EMT and fibrosis in DKD. In nondiabetic chronic kidney disease, canagliflozin promoted ER robustness by maintaining SERCA activity and preventing ER stress response failure, and it contributed to tubular protection.

    DOI: 10.2337/db23-0581

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  • Renal outcomes with sodium‐glucose cotransporter 2 inhibitors in Japanese people with grade 3 chronic kidney disease and type 2 diabetes: Analysis of medical administrative databases 査読 国際誌

    Hiroaki Iijima, Maki Gouda, Hideaki Hida, Kazumi Mori‐Anai, Akiko Takahashi, Ryoichi Minai, Hideki Ninomiya, Yoshiyuki Saito, Atsushi Miyawaki, Jun Wada

    Diabetes, Obesity and Metabolism   26 ( 5 )   1615 - 1623   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: To evaluate whether sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy is associated with a reduction of renal events compared with other glucose-lowering drugs (oGLDs) among Japanese people with type 2 diabetes (T2D) and grade 3 (G3) chronic kidney disease (CKD) in a real-world clinical practice setting. MATERIALS AND METHODS: People with T2D who were newly prescribed an SGLT2i or an oGLD from April 2014 to November 2021 (without prior use of index drugs for ≥ 1 year prior to index date) and G3 CKD (estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m2) were selected from the Medical Data Vision database (MDV-DB) and the Real-World Data database (RWD-DB). SGLT2i and oGLD users were matched (1:1) using propensity score on patient background characteristics. The primary endpoint was a composite of the development of end-stage kidney disease or a sustained decline in eGFR of 50% or more. Hazard ratios (HRs) were estimated using the Cox proportional hazards model. RESULTS: Overall, 3190 (1595 per group) patients in the MDV-DB and 2572 (1286 per group) patients in the RWD-DB were included in the analyses. The composite outcome was significantly lower in the SGLT2i group than in the oGLD group in the MDV-DB (HR 0.49, 95% confidence interval [CI] 0.33 to 0.74, P < 0.001) and in the RWD-DB (HR 0.57, 95% CI 0.37 to 0.88, P = 0.011). CONCLUSIONS: Japanese people with T2D and G3 CKD initiating an SGLT2i had a lower risk of renal events than people initiating an oGLD.

    DOI: 10.1111/dom.15461

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  • Successful treatment for life threatening recurrent non-traumatic rectus sheath hematoma in a case with microscopic polyangiitis with rapidly progressive glomerulonephritis. 査読

    Hiroyuki Nakanoh, Hidemi Takeuchi, Morimoto Shiho, Yuya Terajima, Shugo Okamoto, Yasuhiro Onishi, Keiko Tanaka, Takayuki Katsuyama, Kenji Tsuji, Yoshinori Matsumoto, Katsuyuki Tanabe, Hiroshi Morinaga, Mayu Uka, Koji Tomita, Haruhito A Uchida, Takao Hiraki, Jun Wada

    Internal medicine (Tokyo, Japan)   2024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)  

    A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.

    DOI: 10.2169/internalmedicine.3239-23

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  • A Case of Pseudoxanthoma Elasticum with juvenile-onset hypertension. 査読

    Katsuyoshi Katayama, Haruhito A Uchida, Aya Takehara, Jun Wada

    Internal medicine (Tokyo, Japan)   2024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)  

    DOI: 10.2169/internalmedicine.3050-23

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  • Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study. 査読

    Hiroko Takahashi, Jun Eguchi, Mayu Watanabe, Masanori Nakayama, Jun Wada

    Acta medica Okayama   78 ( 2 )   185 - 191   2024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)  

    The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients.

    DOI: 10.18926/AMO/66927

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  • Effects of HIF-PHD inhibitors in kidney development 査読 国際誌

    Soichiro Haraguchi, Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

    Nephrology Dialysis Transplantation   39 ( 8 )   1368 - 1370   2024年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/ndt/gfae078

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  • The first presentation of a case of nail-patella syndrome newly diagnosed at the onset of rheumatoid arthritis: a case report. 査読 国際誌

    Kazuya Matsumoto, Yoshinori Matsumoto, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Takayuki Katsuyama, Eri Katsuyama, Yoshihisa Nasu, Ken-Ei Sada, Jun Wada

    BMC musculoskeletal disorders   25 ( 1 )   139 - 139   2024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: Nail-patella syndrome (NPS) is a rare autosomal dominant disorder that is characterized by dysplasia of the nails, hypoplasia and/or dislocation of the patella and the presence of iliac horns. Using the CARE guidelines, we present the first reported case of NPS that was newly diagnosed at the onset of rheumatoid arthritis (RA). CASE PRESENTATION: A 74-year-old man was admitted to our hospital due to an 8-month history of arthralgia in bilateral wrists, elbows and fingers. He had a past history of glaucoma and left patella dislocation that had been operatively recentered at the age of 15 years. Laboratory data showed elevated levels of serum C-reactive protein and rheumatoid factor and an elevated titer of anti-SS-A antibodies, while estimated glomerular filtration rate (eGFR), titers of other antibodies and the results of a urinary test were normal. An X-ray showed deformity of bilateral radial heads and the right elbow, and magnetic resonance imaging (MRI) of his hands showed synovitis and erosion in the multiple swollen joints of the wrists and fingers. In addition to these typical features of RA, he had bilateral thumb nail dysplasia with mild hypoplasia of bilateral patellae and iliac horns as shown by the X-ray. He was diagnosed as having autosomal dominant disorder NPS co-existing with RA and he was treated with methotrexate in combination with an oral Janus kinase (JAK) inhibitor, leading to induction of remission. CONCLUSIONS: We have presented a rare case of NPS that was newly diagnosed at the onset of RA. Clinical and radiographic findings of NPS are highlighted in this case report for diagnosing NPS on the basis of typical manifestations.

    DOI: 10.1186/s12891-024-07242-2

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  • A Multicenter, Open-Label, Single-Arm Trial of the Efficacy and Safety of Empagliflozin Treatment for Refractory Diabetes Mellitus with Insulin Resistance (EMPIRE-01). 査読 国際誌

    Yushi Hirota, Yasumasa Kakei, Junta Imai, Hideki Katagiri, Ken Ebihara, Jun Wada, Junichi Suzuki, Tatsuhiko Urakami, Takashi Omori, Wataru Ogawa

    Diabetes therapy : research, treatment and education of diabetes and related disorders   15 ( 2 )   533 - 545   2024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)  

    INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophic diabetes. METHODS: The trial was conducted at five academic centers in Japan and included seven patients with insulin resistance syndrome and one patient with lipoatrophic diabetes. Participants received 10 mg of empagliflozin daily. If the hemoglobin A1c (HbA1c) level was ≥ 7.0% (52 mmol/mol) after 12 weeks, the dose was adjusted to 25 mg. The study duration was 24 weeks, and the primary outcome was the change in HbA1c level by the end of the treatment period. Safety evaluations were performed for all participants. RESULTS: By the end of the 24-week treatment period, the mean HbA1c level for all eight patients had decreased by 0.99 percentage points (10.8 mmol/mol) (95% confidence interval [CI], 0.59 to 1.38 percentage points, 6.6 to 14.9 mmol/mol) and the mean fasting plasma glucose concentration had declined by 63.9 mg/dL (3.55 mmol/L) (95% CI 25.5 to 102.3 mg/dL, 1.42 to 5.68 mmol/L). Continuous glucose monitoring revealed a reduction in mean glucose levels from 164.3 ± 76.1 to 137.6 ± 46.6 mg/dL (9.13 ± 4.23 to 7.65 ± 2.59 mmol/L) as well as an increase in the time in range (70-180 mg/dL) from 58.9 ± 36.1% to 70.8 ± 18.3%. Seventeen mild adverse events were recorded in five individuals throughout the study period. No severe events were reported. The mean body mass showed a slight decrease and the mean serum ketone body concentration showed a slight increase during treatment. CONCLUSION: Our results demonstrate that empagliflozin shows a certain level of efficacy and safety for treatment of insulin resistance syndrome and lipoatrophic diabetes. TRIAL REGISTRATION: jRCTs2051190029 and NCT04018365.

    DOI: 10.1007/s13300-023-01526-x

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  • Late-onset renal variant Fabry disease with R112H mutation and mild increase in plasma globotriaosylsphingosine: a case report. 査読 国際誌

    Keiko Tanaka, Hitoshi Sugiyama, Hiroshi Morinaga, Akifumi Onishi, Katsuyuki Tanabe, Haruhito A Uchida, Hiroki Maruyama, Jun Wada

    Frontiers in medicine   11   1383309 - 1383309   2024年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.

    DOI: 10.3389/fmed.2024.1383309

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  • Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes. 査読 国際誌

    Yuzuki Kano, Satoshi Yamaguchi, Koki Mise, Chieko Kawakita, Yasuhiro Onishi, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Jun Wada

    Kidney360   5 ( 2 )   182 - 194   2023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)  

    BACKGROUND: Inhibition of glucose influx into proximal tubular cells (PTCs) by sodium-glucose co-transporter 2 (SGLT2) inhibitors revealed prominent therapeutic impacts on diabetic kidney disease (DKD). Collectrin (CLTRN) serves as a chaperone for the trafficking of neutral amino acid transporters in the apical membranes of proximal tubular cells. We investigated the beneficial effects of reduced influx of amino acids into proximal tubular cells in diabetes and obesity model of Cltrn-/y mice. METHODS: Cltrn+/y and Cltrn-/y mice at 5 weeks of age were assigned to standard diet- (STD) and streptozotocin and high fat diet-treated (STZ-HFD) groups. RESULTS: At 22-23 weeks of age, body weight and HbA1c levels significantly increased in STZ-HFD-Cltrn+/y compared to STD-Cltrn+/y; however, they were not altered in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. At 20 weeks of age, urinary albumin creatinine ratio (UACR) was significantly reduced in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. Under the treatments with STZ and HFD, the Cltrn gene deficiency caused significant increase in urinary concentration of amino acids such as Gln, His, Gly, Thr, Tyr, Val, Trp, Phe, Ile, Leu and Pro. In proximal tubular cells in STZ-HFD-Cltrn+/y, the enlarged lysosomes with diameter of 10 μm or more were associated with reduced autolysosomes, and the formation of giant lysosomes was prominently suppressed in STZ-HFD-Cltrn-/y. Phospho-mTOR and inactive form of phospho-TFEB were reduced in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. CONCLUSIONS: The reduction of amino acids influx into proximal tubular cells inactivated mTOR, activated TFEB, improved lysosome function, and ameliorated vacuolar formation of PTCs in STZ-HFD-Cltrn-/y mice.

    DOI: 10.34067/KID.0000000000000333

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  • Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study. 査読 国際誌

    Kenji Tsuji, Hiroyuki Nakanoh, Kensaku Takahashi, Takafumi Morita, Yizhen Sang, Kazuhiko Fukushima, Natsumi Matsuoka-Uchiyama, Yasuhiro Onishi, Haruhito A Uchida, Shinji Kitamura, Jun Wada

    Kidney medicine   5 ( 12 )   100733 - 100733   2023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)  

    RATIONALE & OBJECTIVE: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled. PREDICTORS: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score. OUTCOMES: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy. ANALYTICAL APPROACH: Cox proportional hazards model. RESULTS: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91). LIMITATIONS: Single-center study and small sample size. CONCLUSIONS: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy. PLAIN-LANGUAGE SUMMARY: Assessment of kidney biopsies provides crucial information for diagnosis, disease activity, and prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system. Currently, the role of VMC in kidney health and diseases and the clinical significance of VMC variants are poorly understood. In the present study, we have shown that an infiltration of ≥80 inflammatory cells/mm2-VMC area (inflammatory-VMC) is independently associated with kidney disease progression after adjustments for known risk factors of progression. Therefore, assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.

    DOI: 10.1016/j.xkme.2023.100733

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  • Preventive effect of culture supernatant of epithelial-like peritoneal mesothelial cells on peritoneal fibrosis. 査読 国際誌

    Kensaku Takahashi, Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis   44 ( 3 )   8968608231213577 - 8968608231213577   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Peritoneal fibrosis (PF) is a primary reason for discontinuing peritoneal dialysis, which involves characteristic changes of peritoneal mesothelial cells (PMCs). We previously reported preventive effects of implanting human epithelial-like PMCs (P-Epi) for mouse PF caused by mechanical peritoneum scrapings. In the present study, we analysed the preventive effects of culture supernatant of P-Epi in PF. Concentrated culture supernatant of P-Epi or human fibroblast-like PMCs (P-Fibro) or vehicles was injected into nude mice that had undergone mechanical scraping of the parietal and visceral peritoneum, and thickness and amount of adhesions were analysed. Although increased peritoneal adhesions and peritoneum thickening were observed in the vehicle-injected positive control group compared to the sham operation group, fewer number of adhesions and less thickness were observed in the mice treated with culture supernatant of P-Epi, but not P-Fibro, compared to the vehicle-injected positive controls. Immunofluorescent analysis revealed that the expression of extracellular matrix, type I collagen and fibronectin, was lower in the mice treated with culture supernatant of P-Epi than in the vehicle-injected positive controls. In addition, exosomes from P-Epi significantly reduced transforming growth factor-β (TGF-β)-induced expressions of type I collagen and fibronectin in 3T3 fibroblast cells. Collectively, culture supernatant of P-Epi has preventive effects on PF, thus cell therapy is not necessarily required. Further exploration of substances secreted by P-Epi and their protective mechanisms could lead to the development of therapeutic strategies to limit PF.

    DOI: 10.1177/08968608231213577

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  • Neutrophil Elastase Inhibition by Sivelestat (ONO-5046) Attenuates AngII-induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice. 査読 国際誌

    Yoshiko Hada, Haruhito A Uchida, Shugo Okamoto, Nozomu Otaka, Katsuyoshi Katayama, Venkateswaran Subramanian, Alan Daugherty, Jun Wada

    American journal of hypertension   37 ( 5 )   349 - 357   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Abdominal aortic aneurysm (AAA) is an arterial disease characterized by dilatation of the aortic wall. It has been suggested that neutrophil counts and neutrophil elastase activity are associated with AAA. We investigated whether a neutrophil elastase (NE) inhibitor, sivelestat (Siv), had a protective effect against angiotensin II (AngII)-induced AAAs. METHODS: Male apolipoprotein E-deficient mice were assigned into 3 groups: Vehicle+saline, AngII+saline, and AngII+Siv. All mice were administered intraperitoneally with either Siv or vehicle twice daily after AngII infusion. RESULTS: In the 4-week AngII infusion study, plasma NE concentration (p=0.041) and its activity (p=0.011) were elevated by AngII. These increases were attenuated by Siv (concentration:p=0.010, activity:p=0.027). Further, plasma elastase activity was closely correlated with aortic width (R=0.6976, p<0.001). In the 1-week AngII infusion study, plasma and tissue elastase activity increased by AngII (plasma:p=0.034, tissue:p<0.001), but were reduced by Siv (plasma:p=0.014, tissue:p=0.024). AngII increased aortic width (p=0.011) but was attenuated by co-administration of Siv (p=0.022). Moreover, Siv decreased the incidence of AAAs (p=0.009). Elastin fragmentation induced by AngII was reduced by Siv. Many inflammatory cells that were either CD68 or Gr-1 positive were observed in the AngII+saline group, whereas few inflammatory cells were accumulated in the AngII+Siv group. MMP-2 and MMP-9 were enhanced by AngII, but were reduced by Siv. In vitro, MMP-2 activity was induced by human NE (medium:p<0.001, cells:p=0.001), which was attenuated by co-incubation of Siv in medium (p<0.001) and protein of human aortic smooth muscle cells (p=0.001). CONCLUSION: Siv attenuated AngII-induced AAA through the inhibition of NE.

    DOI: 10.1093/ajh/hpad107

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  • Infliximab biosimilar-induced lupus nephritis: A case report. 査読 国際誌

    Kenta Shidahara, Takayuki Katsuyama, Kei Hirose, Kazuya Matsumoto, Shoichi Nawachi, Takato Nakadoi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Eri Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

    Modern rheumatology case reports   8 ( 1 )   74 - 76   2023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)  

    We present a case of microhematuria, proteinuria and hypocomplementemia that developed in a 55-year-old female who was being treated with an infliximab biosimilar (IFX-BS) for rheumatoid arthritis (RA). Renal biopsy showed lupus nephritis (ISN/RPS classification class IV+V). Treatment with the IFX-BS was discontinued, and treatment with prednisolone, hydroxychloroquine and abatacept was started, resulting in clinical remission of lupus nephritis and RA. Although tumor necrosis factor-α (TNF-α) inhibitors are known to induce production of autoantibodies, symptoms are usually limited to skin involvement or arthritis, and renal complications are rare. Physicians should be aware of the risk of lupus nephritis and carefully monitor patients for the development of renal involvement during treatment with TNF-α inhibitors.

    DOI: 10.1093/mrcr/rxad061

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  • Kidney outcomes associated with haematuria and proteinuria trajectories among patients with IgA nephropathy in real-world clinical practice: The Japan Chronic Kidney Disease Database. 査読 国際誌

    Yuichiro Yano, Hajime Nagasu, Hiroshi Kanegae, Masaomi Nangaku, Yosuke Hirakawa, Yuka Sugawara, Naoki Nakagawa, Jun Wada, Hitoshi Sugiyama, Toshiaki Nakano, Takashi Wada, Miho Shimizu, Hitoshi Suzuki, Hiroyuki Komatsu, Naoki Nakashima, Kaori Kitaoka, Ichiei Narita, Hirokazu Okada, Yusuke Suzuki, Naoki Kashihara

    Nephrology (Carlton, Vic.)   29 ( 2 )   65 - 75   2023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)  

    AIM: Among patients with Immunoglobulin A (IgA) nephropathy, we aimed to identify trajectory patterns stratified by the magnitude of haematuria and proteinuria using repeated urine dipstick tests, and assess whether the trajectories were associated with kidney events. METHODS: Using a nationwide multicentre chronic kidney disease (CKD) registry, we analysed data from 889 patients with IgA nephropathy (mean age 49.3 years). The primary outcome was a sustained reduction in eGFR of 50% or more from the index date and thereafter. During follow-up (median 49.0 months), we identified four trajectories (low-stable, moderate-decreasing, moderate-stable, and high-stable) in both urine dipstick haematuria and proteinuria measurements, respectively. RESULTS: In haematuria trajectory analyses, compared to the low-stable group, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) for kidney events were 2.59 (95% CI, 1.48-4.51) for the high-stable, 2.31 (95% CI, 1.19-4.50) for the moderate-stable, and 1.43 (95% CI, (0.72-2.82) for the moderate-decreasing groups, respectively. When each proteinuria trajectory group was subcategorized according to haematuria trajectories, the proteinuria group with high-stable and with modest-stable haematuria trajectories had approximately 2-times higher risk for eGFR reduction ≥50% compared to that with low-stable haematuria trajectory. CONCLUSION: Assessments of both haematuria and proteinuria trajectories using urine dipstick could identify high-risk IgA nephropathy patients.

    DOI: 10.1111/nep.14250

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  • Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes. 査読

    Naoko Kurooka, Jun Eguchi, Jun Wada

    Journal of diabetes investigation   14 ( 10 )   1148 - 1156   2023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)  

    In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.

    DOI: 10.1111/jdi.14056

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  • Role of Semaphorin 3A in Kidney Development and Diseases. 査読 国際誌

    Yizhen Sang, Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

    Diagnostics (Basel, Switzerland)   13 ( 19 )   2023年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases.

    DOI: 10.3390/diagnostics13193038

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  • MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury. 査読 国際誌

    Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

    Diagnostics (Basel, Switzerland)   13 ( 18 )   2023年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

    DOI: 10.3390/diagnostics13182893

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  • The Association of Grit With Burnout Components (Professional Efficacy, Exhaustion, and Cynicism) Among Academic Rheumatologists: The TRUMP 2 -SLE Study. 査読 国際誌

    Yoshia Miyawaki, Ken-Ei Sada, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Keigo Hayashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nao Oguro, Nobuyuki Yajima, Yuichi Ishikawa, Natsuki Sakurai, Chiharu Hidekawa, Ryusuke Yoshimi, Takanori Ichikawa, Dai Kishida, Yasuhiro Shimojima, Jun Wada, Noriaki Kurita

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases   29 ( 6 )   268 - 274   2023年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists. METHODS: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [assistant professor or higher vs lower], marital status, and having children). RESULTS: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04). CONCLUSIONS: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit.

    DOI: 10.1097/RHU.0000000000001989

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  • Pharmacologic inhibition of PARP5, but not that of PARP1 or 2, promotes cytokine production and osteoclastogenesis through different pathways. 査読 国際誌

    Yosuke Asano, Yoshinori Matsumoto, Fang He, Takayuki Katsuyama, Eri Katsuyama, Shigetomo Tsuji, Hiroshi Kamioka, Jose La Rose, Robert Rottapel, Jun Wada

    Clinical and experimental rheumatology   41 ( 9 )   1735 - 1745   2023年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: PARPs, which are members of the poly(ADP-ribose) polymerase superfamily, promote tumorigenesis and tumour-associated inflammation and are thus therapeutic targets for several cancers. The aim of the present study is to investigate the mechanistic insight into the roles PARPs for inflammation. METHODS: Primary murine macrophages were cultured in the presence or absence of the PARP5 inhibitor NVP-TNKS656 to examine the role of PARP5 for cytokine production. RESULTS: In contrast to the roles of other PARPs for induction of inflammation, we found in the present study that pharmacologic inhibition of PARP5 induces production of inflammatory cytokines in primary murine macrophages. We found that treatment with the PARP5 inhibitor NVP-TNKS656 in macrophages enhanced steady-state and LPS-mediated cytokine production through degradation of IκBα and subsequent nuclear translocation of NF-κB. We also found that pharmacologic inhibition of PARP5 stabilises the adaptor protein 3BP2, a substrate of PARP5, and that accelerated cytokine production induced by PARP5 inhibition was rescued in 3BP2-deleted macrophages. Additionally, we found that LPS increases the expression of 3BP2 and AXIN1, a negative regulator of β-catenin, through suppression of PARP5 transcripts in macrophages, leading to further activation of cytokine production and inhibition of β-catenin-mediated cell proliferation, respectively. Lastly, we found that PARP5 inhibition in macrophages promotes osteoclastogenesis through stabilisation of 3BP2 and AXIN1, leading to activation of SRC and suppression of β-catenin, respectively. CONCLUSIONS: Our results show that pharmacologic inhibition of PARP5 against cancers unexpectedly induces adverse autoinflammatory side effects through activation of innate immunity, unlike inhibition of other PARPs.

    DOI: 10.55563/clinexprheumatol/qf55h8

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  • Urinary growth differentiation factor 15 predicts renal function decline in diabetic kidney disease. 査読 国際誌

    Toma Oshita, Shun Watanabe, Takafumi Toyohara, Ryota Kujirai, Koichi Kikuchi, Takehiro Suzuki, Chitose Suzuki, Yotaro Matsumoto, Jun Wada, Yoshihisa Tomioka, Tetsuhiro Tanaka, Takaaki Abe

    Scientific reports   13 ( 1 )   12508 - 12508   2023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)  

    Sensitive biomarkers can enhance the diagnosis, prognosis, and surveillance of chronic kidney disease (CKD), such as diabetic kidney disease (DKD). Plasma growth differentiation factor 15 (GDF15) levels are a novel biomarker for mitochondria-associated diseases; however, it may not be a useful indicator for CKD as its levels increase with declining renal function. This study explores urinary GDF15's potential as a marker for CKD. The plasma and urinary GDF15 as well as 15 uremic toxins were measured in 103 patients with CKD. The relationship between the urinary GDF15-creatinine ratio and the uremic toxins and other clinical characteristics was investigated. Urinary GDF15-creatinine ratios were less related to renal function and uremic toxin levels compared to plasma GDF15. Additionally, the ratios were significantly higher in patients with CKD patients with diabetes (p = 0.0012) and reduced with statin treatment. In a different retrospective DKD cohort study (U-CARE, n = 342), multiple and logistic regression analyses revealed that the baseline urinary GDF15-creatinine ratios predicted a decline in estimated glomerular filtration rate (eGFR) over 2 years. Compared to the plasma GDF15 level, the urinary GDF15-creatinine ratio is less dependent on renal function and sensitively fluctuates with diabetes and statin treatment. It may serve as a good prognostic marker for renal function decline in patients with DKD similar to the urine albumin-creatinine ratio.

    DOI: 10.1038/s41598-023-39657-7

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  • Co-occurrence of Three Systemic Diseases: ANCA-associated Vasculitis, Sjögren's syndrome and Sarcoidosis. 査読

    Kenji Tsuji, Yuka Okuyama, Yosuke Asano, Kimitomo Yamaoka, Shinji Kitamura, Jun Wada

    Internal medicine (Tokyo, Japan)   62 ( 15 )   2215 - 2221   2023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)  

    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Sjögren's syndrome (SjS), and sarcoidosis are systemic diseases targeting multiple organs. While a careful differential diagnosis of these diseases is often required, their co-occurrence in the same patient has been previously reported. We herein report a 58-year-old Japanese man diagnosed with the co-occurrence of three systemic diseases (AAV, SjS, and sarcoidosis) in addition to monoclonal gammopathy of undetermined significance (MGUS), which emphasizes the importance of considering the possible co-occurrence of these diseases as well as their differentiation.

    DOI: 10.2169/internalmedicine.0966-22

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  • Immunosuppressive Treatment for an anti-U1 Ribonucleoprotein Antibody-positive Patient with Pulmonary Arterial Hypertension: A Case Report. 査読

    Kazuya Matsumoto, Yoshia Miyawaki, Takayuki Katsuyama, Takato Nakadoi, Kenta Shidahara, Kei Hirose, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Eri Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Atsushi Mori, Satoshi Akagi, Ken-Ei Sada, Jun Wada

    Internal medicine (Tokyo, Japan)   63 ( 5 )   671 - 676   2023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)  

    A 34-year-old woman with pulmonary arterial hypertension (PAH) was admitted to the hospital. She had been diagnosed with PAH three years earlier and treated with triple vasodilator therapy. She was positive for anti-U1 ribonucleoprotein antibodies but did not show any other symptoms associated with autoimmune diseases. Corticosteroid and cyclophosphamide therapy was administered, suspecting the involvement of immunological pathophysiology. After 3 weeks, the mean pulmonary artery pressure decreased from 50 to 38 mmHg without any change in the vasodilators. Immunosuppressive therapy was effective in this patient with PAH with an anti-U1 ribonucleoprotein-antibody-positive response and might be an option for patients with these specific features.

    DOI: 10.2169/internalmedicine.1407-22

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  • Retroperitoneal Solid Pseudopapillary Tumor Mimicking Adrenal Malignant Tumor in a 67-Year-Old Man. 査読 国際誌

    Takahiro Ishii, Tomohiro Terasaka, Kenji Nishida, Jun Wada

    JCEM case reports   1 ( 4 )   luad090   2023年7月

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    記述言語:英語  

    Solid pseudopapillary tumor (SPT) is a low-grade malignant tumor of the pancreas. SPT typically affects women and can occur in ectopic pancreatic region; however, it also occurs rarely in retroperitoneum. The tumor may be bulky at the time of diagnosis since there is no specific clinical manifestation. Here we present an older male case with retroperitoneal SPT. A 67-year-old man consulted for intermittent fever and lumbago. His basal hormonal profile screened out a functional tumor. Computed tomography (CT) showed a gigantic mass in his left adrenal region. A normal left adrenal gland was not identified, and the tumor's feeding artery was recognized as the left adrenal artery by the contrast-enhanced CT. Adrenal malignant tumor was suspected, and tumor resection was performed. The resected tumor size was 15 × 10 × 9 cm. Histologically, epithelial-like cells with round nuclei and a small amount of eosinophilic cytoplasm proliferated in papillary (around the blood vessels) or uniformly solid form. By immunostaining, tumor cells were vimentin, CD56, cytokeratin AE1/AE3, CD10, β-catenin in the nucleus, cyclin D1, and PgR positive. These findings led to the diagnosis of SPT. Although rare, SPT should be considered as a differential diagnosis in cases of a mass arising from the adrenal region.

    DOI: 10.1210/jcemcr/luad090

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  • NDUFS4 Regulates Cristae Remodeling in Diabetic Kidney Disease 査読 国際誌

    Farhad Danesh, Koki Mise, Jianyin Long, Daniel Galvan, Zengchun Ye, Guizhen Fan, Irina Serysheva, Travis Moore, Jun Wada, Paul Schumacker, Benny Chang

    Nature communications   15 ( 1 )   1965 - 1965   2023年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that conditional male mice with genetic overexpression of Ndufs4 exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify the role of cristae shaping protein STOML2 in linking NDUFS4 with improved cristae morphology. Together, we provide the evidence on the central role of NDUFS4 as a regulator of cristae remodeling and mitochondrial function in kidney podocytes. We propose that targeting NDUFS4 represents a promising approach to slow the progression of DKD.

    DOI: 10.21203/rs.3.rs-3070079/v1

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  • Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones. 査読

    Yusuke Shibata, Jun Eguchi, Jun Wada

    Acta medica Okayama   77 ( 3 )   243 - 254   2023年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BATselective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs.

    DOI: 10.18926/AMO/65489

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  • Effects of Agalsidase Alfa Enzyme Replacement Therapy on Left Ventricular Hypertrophy on Electrocardiogram in a Female Patient with Fabry Disease. 査読

    Kazufumi Nakamura, Hiroshi Morita, Yoichi Takaya, Yukihiro Saito, Toru Miyoshi, Hiroshi Morinaga, Hitoshi Sugiyama, Jun Wada, Hiroshi Ito

    International heart journal   64 ( 3 )   502 - 505   2023年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Fabry disease is an X-linked lysosomal storage disorder caused by defective enzyme activity of α-galactosidase A and treated with enzyme replacement therapy (ERT) with recombinant α-galactosidase. ERT reduces left ventricular mass assessed by echocardiography or magnetic resonance imaging. However, electrocardiogram changes during ERT have not been fully elucidated. In the present case, ERT with agalsidase alfa for 4 years decreased QRS voltage and negative T depth along with a reduction of left ventricular mass and wall thickness and improvement of symptoms in a female patient with Fabry disease. Long-term observation of electrocardiogram changes might be useful for determining the efficacy of ERT in this case.

    DOI: 10.1536/ihj.22-752

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  • Amelioration of nephritis in receptor for advanced glycation end-products (RAGE)-deficient lupus-prone mice through neutrophil extracellular traps. 査読 国際誌

    Haruki Watanabe, Masataka Kubo, Akihiko Taniguchi, Yosuke Asano, Sumie Hiramatsu-Asano, Keiji Ohashi, Sonia Zeggar, Eri Katsuyama, Takayuki Katsuyama, Katsue Sunahori-Watanabe, Ken-Ei Sada, Yoshinori Matsumoto, Yasuhiko Yamamoto, Hiroshi Yamamoto, Myoungsun Son, Jun Wada

    Clinical immunology (Orlando, Fla.)   250   109317 - 109317   2023年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor that regulates inflammation, cell migration, and cell fate. Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease. To understand the function of RAGE in SLE, we generated RAGE-deficient (Ager-/-) lupus-prone mice by backcrossing MRL/MpJ-Faslpr/J (MRL-lpr) mice with Ager-/- C57BL/6 mice. In 18-week-old Ager-/- MRL-lpr, the weights of the spleen and lymph nodes, as well as the frequency of CD3+CD4-CD8- cells, were significantly decreased. Ager-/- MRL-lpr mice had significantly reduced urine albumin/creatinine ratios and markedly improved renal pathological scores. Moreover, neutrophil infiltration and neutrophil extracellular trap formation in the glomerulus were significantly reduced in Ager-/- MRL-lpr. Our study is the first to reveal that RAGE can have a pathologic role in immune cells, particularly neutrophils and T cells, in inflammatory tissues and suggests that the inhibition of RAGE may be a potential therapeutic strategy for SLE.

    DOI: 10.1016/j.clim.2023.109317

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  • Association of alcohol consumption and fatigue in SLE: A cross-sectional study from Lupus Registry of Nationwide Institution (LUNA) cohort. 査読 国際誌

    Yu Katayama, Yoshia Miyawaki, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Keiji Ohashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Nobuyuki Yajima, Yasuhiro Shimojima, Ryusuke Yoshimi, Kunihiro Ichinose, Hiroshi Kajiyama, Michio Fujiwara, Shuzo Sato, Jun Wada

    Lupus   32 ( 4 )   531 - 537   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)  

    OBJECTIVE: Fatigue is one of the most common complaints and is a potentially modifiable issue in systemic lupus erythematosus (SLE). Studies suggest that alcohol consumption has a protective effect against the development of SLE; however, an association between alcohol consumption and fatigue in patients with SLE has not been studied. Here, we assessed whether alcohol consumption was associated with fatigue using lupus patient-reported outcomes (LupusPRO). METHODS: This cross-sectional study, conducted between 2018 and 2019, included 534 patients (median age, 45 years; 87.3% female) from 10 institutions in Japan. The main exposure was alcohol consumption, which was defined as the frequency of drinking [<1 day/month (none group), ≤1 day/week (moderate group), and ≥2 days/week (frequent group)]. The outcome measure was the Pain Vitality domain score in LupusPRO. Multiple regression analysis was performed as the primary analysis after adjusting for confounding factors, such as age, sex, and damage. Subsequently, the same analysis was performed as a sensitivity analysis after multiple imputations (MIs) for missing data (n = 580). RESULTS: In total, 326 (61.0%) patients were categorized into the none group, 121 (22.7%) into the moderate group, and 87 (16.3%) into the frequent group. The frequent group was independently associated with less fatigue compared with none group [β = 5.98 (95% CI 0.19-11.76), p = 0.04], and the results did not substantially deviate after MI. CONCLUSIONS: Frequent drinking was associated with less fatigue, which highlights the need for further longitudinal studies focusing on drinking habits in patients with SLE.

    DOI: 10.1177/09612033231159471

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  • The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study. 査読 国際誌

    Yasuhiro Onishi, Haruhito A Uchida, Yohei Maeshima, Yuka Okuyama, Nozomu Otaka, Haruyo Ujike, Keiko Tanaka, Hidemi Takeuchi, Kenji Tsuji, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Shinji Kitamura, Hitoshi Sugiyama, Kosuke Ota, Keisuke Maruyama, Makoto Hiramatsu, Yoshiyuki Oshiro, Shigeru Morioka, Keiichi Takiue, Kazuyoshi Omori, Masaki Fukushima, Naoyuki Gamou, Hiroshi Hirata, Ryosuke Sato, Hirofumi Makino, Jun Wada

    Journal of personalized medicine   13 ( 4 )   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. METHODS: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. RESULTS: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 ± 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). CONCLUSION: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.

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  • Serum sCD40L and IL-31 in Association with Early Phase of IgA Nephropathy. 査読 国際誌

    Keiko Tanaka, Hitoshi Sugiyama, Hiroshi Morinaga, Masashi Kitagawa, Yuzuki Kano, Yasuhiro Onishi, Koki Mise, Katsuyuki Tanabe, Haruhito A Uchida, Jun Wada

    Journal of clinical medicine   12 ( 5 )   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. RESULTS: Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. CONCLUSIONS: The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.

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  • Association between Urinary Creatinine Excretion and Hypothyroidism in Patients with Chronic Kidney Disease. 査読 国際誌

    Natsumi Matsuoka-Uchiyama, Kenji Tsuji, Kensaku Takahashi, Kazuhiko Fukushima, Hidemi Takeuchi, Shinji Kitamura, Kenichi Inagaki, Haruhito A Uchida, Jun Wada

    Diagnostics (Basel, Switzerland)   13 ( 4 )   2023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)  

    While hypothyroidism increases serum creatinine (Cr) levels, it is uncertain whether the elevation is mediated via a decline in the glomerular filtration rate (GFR) or the reflection of enhanced Cr production from the muscles or both. In the present study, we explored an association between urinary Cr excretion rate (CER) and hypothyroidism. A total of 553 patients with chronic kidney disease were enrolled in a cross-sectional study. Multiple linear regression analysis was performed to explore the association between hypothyroidism and urinary CER. The mean urinary CER was 1.01 ± 0.38 g/day and 121 patients (22%) had hypothyroidism. The multiple linear regression analysis revealed explanatory variables with urinary CER, including age, sex, body mass index, 24 h Cr clearance (24hrCcr), and albumin while hypothyroidism was not considered an independent explanatory variable. In addition, scatter plot analysis with regression fit line representing the association between estimated GFR calculated using s-Cr (eGFRcre) and 24hrCcr revealed that eGFRcre and 24hrCcr had strong correlations with each other in hypothyroid patients as well as euthyroid patients. Collectively, hypothyroidism was not considered an independent explanatory variable for urinary CER in the present study and eGFRcre is a useful marker to evaluate kidney function regardless of the presence of hypothyroidism.

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  • Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice. 査読

    Kaori Oda, Satoshi Miyamoto, Ryo Kodera, Jun Wada, Kenichi Shikata

    Journal of diabetes investigation   14 ( 2 )   205 - 220   2023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)  

    AIMS/INTRODUCTION: Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-Ay /TaJcl (KK-Ay) mice against DKD progression. MATERIALS AND METHODS: Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. RESULTS: Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. CONCLUSIONS: These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.

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  • Genome-wide association study of the risk of chronic kidney disease and kidney-related traits in the Japanese population: J-Kidney-Biobank. 査読 国際誌

    Yuka Sugawara, Yosuke Hirakawa, Hajime Nagasu, Akira Narita, Akihiro Katayama, Jun Wada, Miho Shimizu, Takashi Wada, Hiromasa Kitamura, Toshiaki Nakano, Hideki Yokoi, Motoko Yanagita, Shin Goto, Ichiei Narita, Seizo Koshiba, Gen Tamiya, Masaomi Nangaku, Masayuki Yamamoto, Naoki Kashihara

    Journal of human genetics   68 ( 2 )   55 - 64   2023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)  

    Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m2 or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.

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  • Metformin and Its Immune-Mediated Effects in Various Diseases. 査読 国際誌

    Ichiro Nojima, Jun Wada

    International journal of molecular sciences   24 ( 1 )   2023年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Metformin has been a long-standing prescribed drug for treatment of type 2 diabetes (T2D) and its beneficial effects on virus infection, autoimmune diseases, aging and cancers are also recognized. Metformin modulates the differentiation and activation of various immune-mediated cells such as CD4+ and CD+8 T cells. The activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) pathway may be involved in this process. Recent studies using Extracellular Flux Analyzer demonstrated that metformin alters the activities of glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and glutaminolysis, which tightly link to the modulation of cytokine production in CD4+ and CD+8 T cells in various disease states, such as virus infection, autoimmune diseases, aging and cancers.

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  • Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia. 査読 国際誌

    Akinori Hara, Takashi Wada, Eri Muso, Shoichi Maruyama, Sawako Kato, Kengo Furuichi, Kenichi Yoshimura, Tadashi Toyama, Norihiko Sakai, Hiroyuki Suzuki, Tatsuo Tsukamoto, Mariko Miyazaki, Eiichi Sato, Masanori Abe, Yugo Shibagaki, Ichiei Narita, Shin Goto, Yuichi Sakamaki, Hitoshi Yokoyama, Noriko Mori, Satoshi Tanaka, Yukio Yuzawa, Midori Hasegawa, Takeshi Matsubara, Jun Wada, Katsuyuki Tanabe, Kosuke Masutani, Yasuhiro Abe, Kazuhiko Tsuruya, Shouichi Fujimoto, Shuji Iwatsubo, Akihiro Tsuda, Hitoshi Suzuki, Kenji Kasuno, Yoshio Terada, Takeshi Nakata, Noriaki Iino, Tadashi Sofue, Hitomi Miyata, Toshiaki Nakano, Takayasu Ohtake, Shuzo Kobayashi

    Blood purification   52 ( 4 )   373 - 381   2023年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

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  • E3-ubiquitin ligases and recent progress in osteoimmunology. 査読 国際誌

    Yosuke Asano, Yoshinori Matsumoto, Jun Wada, Robert Rottapel

    Frontiers in immunology   14   1120710 - 1120710   2023年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ubiquitin-mediated proteasomal degradation is a post-transcriptional protein modification that is comprised of various components including the 76-amino acid protein ubiquitin (Ub), Ub-activating enzyme (E1), Ub-conjugating enzyme (E2), ubiquitin ligase (E3), deubiquitinating enzyme (DUB) and proteasome. We and others have recently provided genetic evidence showing that E3-ubiquitin ligases are associated with bone metabolism, the immune system and inflammation through ubiquitylation and subsequent degradation of their substrates. Dysregulation of the E3-ubiquitin ligase RNF146-mediated degradation of the adaptor protein 3BP2 (SH3 domain-binding protein 2) causes cherubism, an autosomal dominant disorder associated with severe inflammatory craniofacial dysmorphia syndrome in children. In this review, on the basis of our discoveries in cherubism, we summarize new insights into the roles of E3-ubiquitin ligases in the development of human disorders caused by an abnormal osteoimmune system by highlighting recent genetic evidence obtained in both human and animal model studies.

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  • Editorial: Myriad types of cell death in nephropathy and their veiled potential. 査読 国際誌

    Jun Wada, Rashmi S Tupe, Isha Sharma

    Frontiers in endocrinology   14   1251148 - 1251148   2023年

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  • A case of sitosterolaemia-caused systemic large-vessel stenosis mimicking Takayasu arteritis in which FDG-PET provided a clue for the differential diagnosis. 査読 国際誌

    Takato Nakadoi, Eri Katsuyama, Kazuya Matsumoto, Kenta Shidahara, Kei Hirose, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Hayato Tada, Jun Wada

    Rheumatology advances in practice   7 ( 3 )   rkad096   2023年

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    記述言語:英語  

    DOI: 10.1093/rap/rkad096

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  • Cover Image, Volume 24, Issue 12

    Takashi Kadowaki, Hiroshi Maegawa, Hirotaka Watada, Daisuke Yabe, Koichi Node, Toyoaki Murohara, Jun Wada

    Diabetes, Obesity and Metabolism   2022年12月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/dom.14114

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  • Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study 査読

    Haruhito A. Uchida, Hirofumi Nakajima, Masami Hashimoto, Akihiko Nakamura, Tomokazu Nunoue, Kazuharu Murakami, Takeshi Hosoya, Kiichi Komoto, Takashi Taguchi, Takaaki Akasaka, Kazuhito Shiosakai, Kotaro Sugimoto, Jun Wada

    ADVANCES IN THERAPY   39 ( 11 )   5158 - 5175   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12325-022-02294-z

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  • A case of recurrent IgG4-related disease successfully treated with belimumab after remission of systemic lupus erythematosus 査読

    Yu Katayama, Takayuki Katsuyama, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

    RHEUMATOLOGY   61 ( 10 )   E308 - E310   2022年10月

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  • Effects of Wnt-beta-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells 査読

    Eisaku Morimoto, Kenichi Inagaki, Motoshi Komatsubara, Tomohiro Terasaka, Yoshihiko Itoh, Satoshi Fujisawa, Erika Sasaki, Yuki Nishiyama, Takayuki Hara, Jun Wada

    JOURNAL OF THE ENDOCRINE SOCIETY   6 ( 10 )   2022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)  

    DOI: 10.1210/jendso/bvac121

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  • Simulation for ultrasound-guided renal biopsy using boiled egg 査読

    Kenji Tsuji, Shinji Kitamura, Haruhito A. Uchida, Jun Wada

    NEPHROLOGY   27 ( 9 )   753 - 757   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/nep.14079

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  • The association between hypothyroidism and proteinuria in patients with chronic kidney disease: a cross-sectional study 査読

    Natsumi Matsuoka-Uchiyama, Kenji Tsuji, Yizhen Sang, Kensaku Takahashi, Kazuhiko Fukushima, Hidemi Takeuchi, Kenichi Inagaki, Haruhito A. Uchida, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada

    SCIENTIFIC REPORTS   12 ( 1 )   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-022-19226-0

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  • Cilostazol Attenuates AngII-Induced Cardiac Fibrosis in apoE Deficient Mice 査読

    Yoshiko Hada, Haruhito A. Uchida, Ryoko Umebayashi, Masashi Yoshida, Jun Wada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   23 ( 16 )   2022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)  

    DOI: 10.3390/ijms23169065

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  • Interconnection between cardiovascular, renal and metabolic disorders: A narrative review with a focus on Japan 査読

    Takashi Kadowaki, Hiroshi Maegawa, Hirotaka Watada, Daisuke Yabe, Koichi Node, Toyoaki Murohara, Jun Wada

    DIABETES OBESITY & METABOLISM   2022年8月

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  • Edaravone Attenuated Angiotensin II-Induced Atherosclerosis and Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice 査読

    Haruhito A. Uchida, Tetsuharu Takatsuka, Yoshiko Hada, Ryoko Umebayashi, Hidemi Takeuchi, Kenichi Shikata, Venkateswaran Subramanian, Alan Daugherty, Jun Wada

    BIOMOLECULES   12 ( 8 )   2022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)  

    DOI: 10.3390/biom12081117

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  • Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus. 査読

    Sumie Hiramatsu-Asano, Jun Wada

    Acta medica Okayama   76 ( 4 )   359 - 371   2022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)  

    Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE.

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  • Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study 査読

    Yuka Sugawara, Yosuke Hirakawa, Koki Mise, Kosuke Kashiwabara, Ko Hanai, Satoshi Yamaguchi, Akihiro Katayama, Yasuhiro Onishi, Yui Yoshida, Naoki Kashihara, Yutaka Matsuyama, Tetsuya Babazono, Masaomi Nangaku, Jun Wada

    BIOMARKERS IN MEDICINE   16 ( 10 )   759 - 770   2022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)  

    DOI: 10.2217/bmm-2021-1104

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  • Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle. 査読

    Masafumi Tenta, Jun Eguchi, Jun Wada

    Acta medica Okayama   76 ( 3 )   235 - 245   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The combination of sarcopenia and obesity (sarcopenic obesity) is associated with the development of metabolic syndrome and cardiovascular events. The molecular pathways that develop sarcopenic obesity have studied intensively. Transmembrane protein 97 (TMEM97) is 176 amino acids conserved integral membrane protein with four transmembrane domains that is expressed in several types of cancer. Its physiological significance in adipose tissue and skeletal muscle has been unclear. We studied TMEM97-transgenic mice and mice lacking TMEM97, and our findings indicate that TMEM97 expression is regulated in adipose tissue and skeletal muscle from obesity. TMEM97 represses adipogenesis and promotes myogenesis in vitro. Fat-specific TMEM97 transgenic mice showed systemic insulin resistance. Mice overexpressing TMEM97 in skeletal muscle exhibited systemic insulin resistance. Mice lacking TMEM97 were protected against diet-induced obesity and insulin resistance. These phenotypes are associated with the effects of TMEM97 on inflammation genes in adipose tissue and skeletal muscle. Our findings indicates that there is a link between TMEM97 and chronic inflammation in obesity.

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  • Potential Strategies for Kidney Regeneration With Stem Cells: An Overview 査読

    Kenji Tsuji, Shinji Kitamura, Jun Wada

    FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY   10   2022年5月

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  • Vasohibin-1 has α-tubulin detyrosinating activity in glomerular podocytes. 査読 国際誌

    Tomoyo Mifune, Katsuyuki Tanabe, Yuri Nakashima, Satoshi Tanimura, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

    Biochemical and biophysical research communications   599   93 - 99   2022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)  

    Podocytes are highly specialized epithelial cells in glomeruli, with a complex morphology composed of a cell body, primary processes, and foot processes, which maintain barrier function in glomerular filtration. The microtubule-based cytoskeleton is necessary for podocyte morphology. Microtubule structure and function can be affected by post-translational modification of tubulin, including detyrosination. Recent studies have shown that vasohibin-1 (VASH1), an antiangiogenic factor, has tubulin carboxypeptidase activity that causes detyrosination of α-tubulin. We aimed to examine the role of VASH1 in regulating α-tubulin detyrosination in podocytes and the potential involvement of VASH1 deficiency in renal morphology. In normal mouse kidneys, detyrosinated α-tubulin was mainly identified in glomeruli, especially in podocytes; meanwhile, in cultured immortalized podocytes, α-tubulin detyrosination was promoted with cell differentiation. Notably, α-tubulin detyrosination in glomeruli was diminished in Vash1 homozygous knockout (Vash1-/-) mice, and knockdown of VASH1 in cultured podocytes prevented α-tubulin detyrosination. Although VASH1 deficiency-induced downregulation of detyrosination caused no remarkable glomerular lesions, urinary albuminuria excretion and glomerular volume were significantly higher in Vash1-/- mice than in wild-type mice. Furthermore, decreased glomerular nephrin expression and narrower slit diaphragms width were observed in Vash1-/- mice. Taken together, we demonstrated that α-tubulin detyrosination in podocytes was mainly regulated by VASH1 and that VASH1 deficiency-mediated decreases in α-tubulin detyrosination led to minor alterations in podocyte morphology and predisposition to albuminuria. VASH1 expression and α-tubulin detyrosination may be novel targets for maintaining glomerular filtration barrier integrity.

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  • Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells 査読

    Masayoshi Suda, Ippei Shimizu, Goro Katsuumi, Chieh Lun Hsiao, Yohko Yoshida, Naomi Matsumoto, Yutaka Yoshida, Akihiro Katayama, Jun Wada, Masahide Seki, Yutaka Suzuki, Shujiro Okuda, Kazuyuki Ozaki, Mayumi Nakanishi-Matsui, Tohru Minamino

    SCIENTIFIC REPORTS   12 ( 1 )   2022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)  

    DOI: 10.1038/s41598-022-10522-3

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  • Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation 査読

    Kenta Ikeda, Shin Morizane, Takahiko Akagi, Sumie Hiramatsu-Asano, Kota Tachibana, Ayano Yahagi, Masanori Iseki, Hideaki Kaneto, Jun Wada, Katsuhiko Ishihara, Yoshitaka Morita, Tomoyuki Mukai

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   23 ( 8 )   2022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)  

    DOI: 10.3390/ijms23084312

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  • Tankyrase represses autoinflammation through the attenuation of TLR2 signaling 査読

    Yoshinori Matsumoto, Ioannis D. Dimitriou, Jose La Rose, Melissa Lim, Susan Camilleri, Napoleon Law, Hibret A. Adissu, Jiefei Tong, Michael F. Moran, Andrzej Chruscinski, Fang He, Yosuke Asano, Takayuki Katsuyama, Ken-Ei Sada, Jun Wada, Robert Rottapel

    JOURNAL OF CLINICAL INVESTIGATION   132 ( 7 )   2022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)  

    DOI: 10.1172/JCI140869

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  • Kidney cyst infection through a fistula between bladder and retroperitoneal abscess in a polycystic kidney disease patient 査読

    Takato Nakadoi, Kenji Tsuji, Takehiro Iwata, Eriko Eto, Hisashi Masuyama, Koji Tomita, Takao Hiraki, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada

    NEPHROLOGY   27 ( 4 )   383 - 384   2022年4月

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  • Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study 査読

    Naoko Kurooka, Jun Eguchi, Kazutoshi Murakami, Shinji Kamei, Toru Kikutsuji, Sakiko Sasaki, Akiho Seki, Satoshi Yamaguchi, Ichiro Nojima, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Haruhito A. Uchida, Atsuko Nakatsuka, Kenichi Shikata, Jun Wada

    JOURNAL OF CLINICAL LIPIDOLOGY   16 ( 2 )   237 - 245   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jacl.2022.01.006

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  • Silica-associated systemic lupus erythematosus with lupus nephritis and lupus pneumonitis A case report and a systematic review of the literature 査読

    Kazuhiko Fukushima, Haruhito A. Uchida, Yasuko Fuchimoto, Tomoyo Mifune, Mayu Watanabe, Kenji Tsuji, Katsuyuki Tanabe, Masaru Kinomura, Shinji Kitamura, Yosuke Miyamoto, Sae Wada, Taisaku Koyanagi, Hitoshi Sugiyama, Takumi Kishimoto, Jun Wada

    MEDICINE   101 ( 7 )   2022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)  

    DOI: 10.1097/MD.0000000000028872

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  • Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray 査読

    Yasuhiro Onishi, Koki Mise, Chieko Kawakita, Haruhito A. Uchida, Hitoshi Sugiyama, Ryosuke Sugawara, Satoshi Yamaguchi, Michihiro Yoshida, Toshiharu Mitsuhashi, Masao Yamada, Jun Hirabayashi, Jun Wada

    AMERICAN JOURNAL OF NEPHROLOGY   53 ( 1 )   10 - 20   2022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)  

    DOI: 10.1159/000520998

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  • Prevalence of Chronic Kidney Disease and Variation of Its Risk Factors by the Regions in Okayama Prefecture 査読

    Ryoko Umebayashi, Haruhito Adam Uchida, Natsumi Matsuoka-Uchiyama, Hitoshi Sugiyama, Jun Wada

    JOURNAL OF PERSONALIZED MEDICINE   12 ( 1 )   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/jpm12010097

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  • The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study 査読

    Natsumi Matsuoka-Uchiyama, Haruhito A. Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenichi Shikata, Jun Wada

    JOURNAL OF DIABETES RESEARCH   2022   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2022/3157841

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  • Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4 査読

    Satoshi Yamaguchi, Dongxiao Zhang, Akihiro Katayama, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Jun Wada

    FRONTIERS IN ENDOCRINOLOGY   12   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fendo.2021.750261

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  • Real-world data on vitamin D supplementation and its impacts in systemic lupus erythematosus: Cross-sectional analysis of a lupus registry of nationwide institutions (LUNA). 査読 国際誌

    Keigo Hayashi, Ken-Ei Sada, Yosuke Asano, Yu Katayama, Keiji Ohashi, Michiko Morishita, Yoshia Miyawaki, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Nobuyuki Yajima, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Jun Wada

    PloS one   17 ( 6 )   e0270569   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE. METHODS: A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control. RESULTS: Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups. CONCLUSIONS: Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.

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  • Mesenchymal stem cells-derived extracellular vesicles as 'natural' drug delivery system for tissue regeneration 査読

    Kenji Tsuji, Shinji Kitamura, Jun Wada

    BIOCELL   46 ( 4 )   899 - 902   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.32604/biocell.2022.018594

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  • Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism. 査読 国際誌

    Natsumi Uchiyama-Matsuoka, Kenji Tsuji, Haruhito A Uchida, Shinji Kitamura, Yoshihiko Itoh, Yuki Nishiyama, Eisaku Morimoto, Satoshi Fujisawa, Tomohiro Terasaka, Takayuki Hara, Kanako Ogura-Ochi, Kenichi Inagaki, Jun Wada

    Frontiers in endocrinology   13   1048863 - 1048863   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism. METHODS: Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. RESULTS: Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 m2) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m2). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. CONCLUSIONS: We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.

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  • THE MINIMALLY IMPORTANT DIFFERENCE AS THE INTERPRETABILITY OF EMOTIONAL HEALTH DOMAIN IN JAPANESE VERSION OF LUPUSPRO FOR SLE PATIENTS; PRELIMINARY RESULTS OF A PROSPECTIVE COHORT STUDY

    Jun Wada

    Annals of the Rheumatic Diseases   2022年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/ANNRHEUMDIS-2022-EULAR.1406

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  • First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency

    Jun Wada

    Heliyon   2022年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/J.HELIYON.2022.E11271

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  • The Beneficial Effect of Personalized Lifestyle Intervention in Chronic Kidney Disease Follow-Up Project for National Health Insurance Specific Health Checkup: A Five-Year Community-Based Cohort Study

    Jun Wada

    Medicina   2022年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/MEDICINA58111529

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  • Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice 査読

    Jun Wada

    Nature Aging   1 ( 12 )   1117 - 1126   2021年12月

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  • Commentary on Intraglumerular dysfunction predicts kidney failure in the type 2 diabetes 査読

    Jun Wada

    JOURNAL OF DIABETES INVESTIGATION   12 ( 12 )   2124 - 2125   2021年12月

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  • Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling 査読

    Yizhen Sang, Kenji Tsuji, Kazuhiko Fukushima, Kensaku Takahashi, Shinji Kitamura, Jun Wada

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   321 ( 6 )   F740 - F756   2021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)  

    DOI: 10.1152/ajprenal.00234.2021

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  • Presence of decoy cells for 6 months on urine cytology efficiently predicts BK virus nephropathy in renal transplant recipients 査読

    Takanori Sekito, Motoo Araki, Kasumi Yoshinaga, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Tanabe, Hidemi Takeuchi, Hiroshi Morinaga, Masashi Kitagawa, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Hiroyuki Yanai, Yasutomo Nasu

    INTERNATIONAL JOURNAL OF UROLOGY   28 ( 12 )   1240 - 1246   2021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)  

    DOI: 10.1111/iju.14679

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  • Management of corticosteroid-dependent eosinophilic interstitial nephritis A case report 査読

    Katsuyuki Tanabe, Natsumi Matsuoka-Uchiyama, Tomoyo Mifune, Chieko Kawakita, Hitoshi Sugiyama, Jun Wada

    MEDICINE   100 ( 50 )   2021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)  

    DOI: 10.1097/MD.0000000000028252

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  • Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database 査読

    Hajime Nagasu, Yuichiro Yano, Hiroshi Kanegae, Hiddo J. L. Heerspink, Masaomi Nangaku, Yosuke Hirakawa, Yuka Sugawara, Naoki Nakagawa, Yuji Tani, Jun Wada, Hitoshi Sugiyama, Kazuhiko Tsuruya, Toshiaki Nakano, Shoichi Maruyama, Takashi Wada, Kunihiro Yamagata, Ichiei Narita, Kouichi Tamura, Motoko Yanagita, Yoshio Terada, Takashi Shigematsu, Tadashi Sofue, Takafumi Ito, Hirokazu Okada, Naoki Nakashima, Hiromi Kataoka, Kazuhiko Ohe, Mihoko Okada, Seiji Itano, Akira Nishiyama, Eiichiro Kanda, Kohjiro Ueki, Naoki Kashihara

    DIABETES CARE   44 ( 11 )   2542 - 2551   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/dc21-1081

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  • Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control (vol 12, 727915, 2021) 査読

    Dongxiao Zhang, Satoshi Yamaguchi, Xinhao Zhang, Boxuan Yang, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Takeshi Y. Hiyama, Atsunori Kamiya, Jun Wada

    FRONTIERS IN ENDOCRINOLOGY   12   2021年11月

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  • Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms 査読

    Shogo Watari, Motoo Araki, Jun Matsumoto, Kasumi Yoshinaga, Takanori Sekito, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Koichiro Wada, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Noritaka Ariyoshi, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    DRUG METABOLISM AND PHARMACOKINETICS   40   2021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)  

    DOI: 10.1016/j.dmpk.2021.100407

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  • Sodium-Glucose Cotransporter 2 Inhibitors Work as a "Regulator" of Autophagic Activity in Overnutrition Diseases 査読

    Kazuhiko Fukushima, Shinji Kitamura, Kenji Tsuji, Jun Wada

    FRONTIERS IN PHARMACOLOGY   12   2021年10月

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  • Feasible kidney donation with living marginal donors, including diabetes mellitus 査読

    Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Takanori Sekito, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Katsuyuki Tanabe, Hidemi Takeuchi, Masashi Kitagawa, Shinji Kitamura, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    IMMUNITY INFLAMMATION AND DISEASE   9 ( 3 )   1061 - 1068   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/iid3.470

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  • Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases 査読

    Noriko Fujiwara, Mayu Watanabe, Akihiro Katayama, Yohei Noda, Jun Eguchi, Hitomi Kataoka, Shunsuke Kagawa, Jun Wada

    CLINICAL CASE REPORTS   9 ( 9 )   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/ccr3.4574

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  • Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 (vol 11, 5991, 2021) 査読

    Tomokazu Nunoue, Satoshi Yamaguchi, Sanae Teshigawara, Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Toshiro Niki, Jun Wada

    SCIENTIFIC REPORTS   11 ( 1 )   2021年9月

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  • Total vascular resistance, augmentation index, and augmentation pressure increase in patients with peripheral artery disease. 査読 国際誌

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

    Medicine   100 ( 32 )   e26931   2021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)  

    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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  • GENOME-WIDE ASSOCIATION STUDY FOR THE ONSET OF CHRONIC KIDNEY DISEASE IN JAPANESE POPULATION 査読

    Yuka Sugawara, Yosuke Hirakawa, Hajime Nagasu, Akira Narita, Jun Wada, Takashi Wada, Toshiaki Nakano, Motoko Yanagita, Ichiei Narita, Seizo Koshiba, Gen Tamiya, Masaomi Nangaku, Masayuki Yamamoto, Naoki Kashihara

    NEPHROLOGY   26   7 - 8   2021年8月

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    記述言語:英語  

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  • Successful deceased donor kidney transplantation to a recipient with a history of COVID-19 treatment 査読

    Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Kou Hasegawa, Takanori Sekito, Shuji Miyake, Shogo Watari, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Katsuyuki Tanabe, Hidemi Takeuchi, Yuri Nakashima, Masaru Kinomura, Herik Acosta, Yosuke Mitsui, Risa Kubota, Hirochika Nakajima, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Fumio Otsuka, Jun Wada, Yasutomo Nasu

    JOURNAL OF INFECTION AND CHEMOTHERAPY   27 ( 7 )   1097 - 1101   2021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)  

    DOI: 10.1016/j.jiac.2021.03.018

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  • RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion (vol 11, 665273, 2021) 査読

    Fang He, Yoshinori Matsumoto, Yosuke Asano, Yuriko Yamamura, Takayuki Katsuyama, Jose La Rose, Nahoko Tomonobu, Ni Luh Gede Yoni Komalasari, Masakiyo Sakaguchi, Robert Rottapel, Jun Wada

    FRONTIERS IN ONCOLOGY   11   2021年7月

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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 査読

    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 )   2021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)  

    DOI: 10.1038/s41598-021-94467-z

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  • The effect of Humanitude care methodology on improving empathy: a six-year longitudinal study of medical students in Japan 査読

    Yusuke Fukuyasu, Hitomi U. Kataoka, Miwako Honda, Toshihide Iwase, Hiroko Ogawa, Masaru Sato, Mayu Watanabe, Chikako Fujii, Jun Wada, Jennifer DeSantis, Mohammadreza Hojat, Joseph S. Gonnella

    BMC MEDICAL EDUCATION   21 ( 1 )   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12909-021-02773-x

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  • ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study 査読

    Shogo Watari, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    TRANSPLANTATION PROCEEDINGS   53 ( 5 )   1494 - 1500   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.transproceed.2021.03.043

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  • 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) 査読

    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   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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 査読

    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年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/ajh/hpaa181

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  • Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells 査読

    Satoshi Fujisawa, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Takahiro Nada, Jun Wada, Fumio Otsuka

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   22 ( 9 )   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms22094553

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  • Endonuclease increases efficiency of osteoblast isolation from murine calvariae. 査読 国際誌

    Yosuke Asano, Yoshinori Matsumoto, Jose La Rose, Fang He, Takayuki Katsuyama, Wang Ziyi, Shigetomo Tsuji, Hiroshi Kamioka, Robert Rottapel, Jun Wada

    Scientific reports   11 ( 1 )   8502 - 8502   2021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)  

    DOI: 10.1038/s41598-021-87716-8

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  • THE IMPACT OF BLOOD PRESSURE MANAGEMENT IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A MULTICENTER PROSPECTIVE COHORT STUDY IN JAPAN 査読

    Mariko Nishiwaki, Haruhito A. Uchida, Nozomu Otaka, Yoshiko Hada, Yasuhiro Onishi, Natsumi Uchiyama, Shugo Okamoto, Rika Takemoto, Masashi Kitagawa, Hitoshi Sugiyama, Chie Saito, Kunihiro Yamagata, Jun Wada

    JOURNAL OF HYPERTENSION   39   E122 - E123   2021年4月

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    記述言語:英語  

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  • Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Macrophage 査読

    Yoshiko Hada, Haruhito A. Uchida, Jun Wada

    BIOMED RESEARCH INTERNATIONAL   2021   2021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)  

    DOI: 10.1155/2021/5570885

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  • Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study. 査読 国際誌

    Yoshia Miyawaki, Sayaka Shimizu, Yusuke Ogawa, Ken-Ei Sada, Yu Katayama, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu-Asano, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nobuyuki Yajima, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Hajime Yamazaki, Yosuke Yamamoto, Jun Wada, Shunichi Fukuhara

    Arthritis research & therapy   23 ( 1 )   79 - 79   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS). METHODS: This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of ≥ 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use. RESULTS: Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (β coefficient = - 2.54 [95% confidence interval - 4.48 to - 0.60], P = 0.01). CONCLUSIONS: Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health.

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  • A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease 査読

    Atsuko Nakatsuka, Satoshi Yamaguchi, Jun Eguchi, Shigeru Kakuta, Yoichiro Iwakura, Hitoshi Sugiyama, Jun Wada

    COMMUNICATIONS BIOLOGY   4 ( 1 )   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s42003-021-01902-y

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  • Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy 査読

    Chieko Kawakita, Koki Mise, Yasuhiro Onishi, Hitoshi Sugiyama, Michihiro Yoshida, Masao Yamada, Jun Wada

    SCIENTIFIC REPORTS   11 ( 1 )   2021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)  

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  • Granulomatosis with polyangiitis with obstructive pneumonia progressing to hypertrophic pachymeningitis: A case report. 査読 国際誌

    Keigo Hayashi, Haruki Watanabe, Yuriko Yamamura, Yosuke Asano, Yu Katayama, Sumie Hiramatsu-Asano, Keiji Ohashi, Michiko Morishita, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

    Medicine   100 ( 3 )   e24028   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    RATIONALE: Bronchial involvement alone is a rare initial manifestation of granulomatosis with polyangiitis (GPA). Herein, we report a case of refractory GPA with obstructive pneumonia caused by bronchial involvement. PATIENT CONCERNS: A 65-year-old man complained of a 2-week cough and fever. DIAGNOSES: Considering the presence of opacities and multiple consolidations in both lungs due to obstruction or stenosis on the bronchus, which did not respond to antibiotics, and proteinase-3-antineutrophil cytoplasmic autoantibody positivity, he was diagnosed with GPA. Positron emission tomography- computed tomography scan revealed no abnormal findings in the upper respiratory tract. INTERVENTIONS: He was treated with prednisolone (PSL, 50 mg/d) and intravenous cyclophosphamide. OUTCOMES: His general and respiratory symptoms improved. However, 8 weeks after PSL treatment at 20 mg/d, he developed a relapse of vasculitis along with sinusitis and hypertrophic pachymeningitis. Hence, PSL treatment was resumed to 50 mg/d, and weekly administration of rituximab was initiated. Consequently, the symptoms gradually mitigated. LESSONS: GPA with bronchial involvement is often intractable and requires careful follow-up, which should include upper respiratory tract and hypertrophic pachymeningitis assessment.

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  • Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia 査読

    Takashi Wada, Akinori Hara, Eri Muso, Shoichi Maruyama, Sawako Kato, Kengo Furuichi, Kenichi Yoshimura, Tadashi Toyama, Norihiko Sakai, Hiroyuki Suzuki, Tatsuo Tsukamoto, Mariko Miyazaki, Eiichi Sato, Masanori Abe, Yugo Shibagaki, Ichiei Narita, Shin Goto, Yuichi Sakamaki, Hitoshi Yokoyama, Noriko Mori, Yukio Yuzawa, Midori Hasegawa, Takeshi Matsubara, Jun Wada, Katsuyuki Tanabe, Kosuke Masutani, Yasuhiro Abe, Kazuhiko Tsuruya, Shouichi Fujimoto, Shuji Iwatsubo, Akihiro Tsuda, Hitoshi Suzuki, Kenji Kasuno, Yoshio Terada, Takeshi Nakata, Noriaki Iino, Tadashi Sofue, Hitomi Miyata, Toshiaki Nakano, Takayasu Ohtake, Shuzo Kobayashi

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   25 ( 1 )   1 - 8   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10157-020-01959-9

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  • MicroRNAs as Biomarkers for Nephrotic Syndrome 査読

    Kenji Tsuji, Shinji Kitamura, Jun Wada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   22 ( 1 )   2021年1月

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  • The resolution of immunofluorescent pathological images affects diagnosis for not only artificial intelligence but also human 査読

    Kensaku Takahashi, Shinji Kitamura, Kazuhiko Fukushima, Yizhen Sang, Kenji Tsuji, Jun Wada

    Journal of Nephropathology   10 ( 3 )   2021年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.34172/jnp.2021.26

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  • Current Status of Familial LCAT Deficiency in Japan 査読

    Masayuki Kuroda, Hideaki Bujo, Koutaro Yokote, Takeyoshi Murano, Takashi Yamaguchi, Masatsune Ogura, Katsunori Ikewaki, Masahiro Koseki, Yasuo Takeuchi, Atsuko Nakatsuka, Mika Hori, Kota Matsuki, Takashi Miida, Shinji Yokoyama, Jun Wada, Mariko Harada-Shiba

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   28 ( 7 )   679 - 691   2021年

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  • Acute Kidney Injury Caused by Evans Syndrome with Systemic Lupus Erythematosus and Systemic Sclerosis 査読

    Natsumi Matsuoka, Haruki Watanabe, Naoko Kurooka, Sumari Kato, Chika Higashi, Katsuyuki Tanabe, Masaru Kinomura, Nobuharu Fujii, Ken-Ei Sada, Hitoshi Sugiyama, Jun Wada

    INTERNAL MEDICINE   60 ( 7 )   1055 - 1060   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.5976-20

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  • Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes 査読

    The Mon La, Hiromi Tachibana, Shun-Ai Li, Tadashi Abe, Sayaka Seiriki, Hikaru Nagaoka, Eizo Takashima, Tetsuya Takeda, Daisuke Ogawa, Shin-ichi Makino, Katsuhiko Asanuma, Masami Watanabe, Xuefei Tian, Shuta Ishibe, Ayuko Sakane, Takuya Sasaki, Jun Wada, Kohji Takei, Hiroshi Yamada

    FASEB JOURNAL   34 ( 12 )   16449 - 16463   2020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)  

    DOI: 10.1096/fj.202001240RR

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  • Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection 査読

    Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Haruhito Adam Uchida, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    INTERNATIONAL JOURNAL OF UROLOGY   27 ( 12 )   1136 - 1142   2020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)  

    DOI: 10.1111/iju.14382

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  • Takayasu phlebitis 査読

    Yu Katayama, Yoshinori Matsumoto, Yuriko Yamamura, Yosuke Asano, Keigo Hayashi, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Narazaki, Ken-Ei Sada, Jun Wada

    RHEUMATOLOGY   59 ( 12 )   E131 - E133   2020年12月

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  • Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis. 査読 国際誌

    Keigo Hayashi, Ken-Ei Sada, Yosuke Asano, Sumie Hiramatsu Asano, Yuriko Yamamura, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Narazaki, Yoshinori Matsumoto, Jun Wada

    Scientific reports   10 ( 1 )   18715 - 18715   2020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)  

    Renal impairment is a major concern in patients taking high-dose methotrexate (MTX) for malignancy, but it has not been fully explored in rheumatoid arthritis (RA) patients taking low-dose MTX. This study aimed to elucidate the dose-dependent effects of MTX on the renal function of patients with RA. We retrospectively reviewed 502 consecutive RA patients who were prescribed MTX for ≥ 1 year at Okayama University Hospital between 2006 and 2018. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over 1 year. The association between MTX dosage (< 8, 8-12, and ≥ 12 mg/week) and the change in eGFR was evaluated using multiple linear regression analysis with adjustment for possible confounding factors including age, sex, disease duration, body weight, comorbidity, baseline eGFR, concomitant treatment, and disease activity. Mean patient age was 63 years; 394 (78%) were female. Median disease duration was 77 months, while mean MTX dosage was 8.6 mg/week. The last 1-year change of eGFR (mean ± SD) in patients treated with MTX < 8 (n = 186), 8-12 (n = 219), ≥ 12 mg/week (n = 97) decreased by 0.2 ± 7.3, 0.6 ± 8.6, and 4.5 ± 7.9 mL/min/1.73 m2/year, respectively (p < 0.0001). After adjustment for the confounding factors, MTX ≥ 12 mg/week was still correlated with a decrease in 1-year eGFR (beta-coefficient: - 2.5; 95% confidence interval, - 4.3 to - 0.6; p = 0.0089) in contrast to MTX 8-12 mg/week. Careful monitoring of renal function is required in patients with MTX ≥ 12 mg/week over the course of RA treatment regardless of disease duration.

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  • Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice 査読

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

    CLINICAL SCIENCE   134 ( 20 )   2771 - 2787   2020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)  

    DOI: 10.1042/CS20201036

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  • Multicentric Reticulohistiocytosis in a Patient with Hand Contracture. 査読

    Tomoko Kawabata, Ken-Ei Sada, Haruki Watanabe, Jun Wada

    Internal medicine (Tokyo, Japan)   59 ( 18 )   2337 - 2338   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.4934-20

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  • Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis 査読

    Ichiro Nojima, Shingo Eikawa, Nahoko Tomonobu, Yoshiko Hada, Nobuo Kajitani, Sanae Teshigawara, Satoshi Miyamoto, Atsuhito Tone, Haruhito A. Uchida, Atsuko Nakatsuka, Jun Eguchi, Kenichi Shikata, Heiichiro Udono, Jun Wada

    SCIENTIFIC REPORTS   10 ( 1 )   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells 査読

    Natsumi Matsuoka-Uchiyama, Kenji Tsuji, Kazuhiko Fukushima, Shinji Kitamura, Haruhito A. Uchida, Hitoshi Sugiyama, Naoki Takahashi, Masayuki Iwano, Jun Wada

    KIDNEY INTERNATIONAL REPORTS   5 ( 9 )   1576 - 1580   2020年9月

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  • Podocytopathy as 'stand-alone' involvement in systemic lupus erythematosus: a case report. 査読 国際誌

    Kenji Tsuji, Yoko Takatsu, Yu Katayama, Kazuhiko Fukushima, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada

    Lupus   29 ( 9 )   1148 - 1150   2020年8月

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  • Tubulointerstitial Nephritis and Uveitis Caused by Sjögren Syndrome Without Dryness. 査読 国際誌

    Soichiro Sugitani, Kenji Tsuji, Toshio Yamanari, Yoichi Hasegawa, Kentaro Inoue, Yuka Sogabe, Yukari Nakano, Shinji Kitamura, Tsutomu Ishizu, Jun Wada

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases   2020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)  

    DOI: 10.1097/RHU.0000000000001505

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  • Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors. 査読 国際誌

    Kenji Tsuji, Shinji Kitamura, Yizhen Sang, Kazuhiko Fukushima, Jun Wada

    Stem cell research   46   101865 - 101865   2020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)  

    Adult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.

    DOI: 10.1016/j.scr.2020.101865

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  • Deep Learning Could Diagnose Diabetic Nephropathy with Renal Pathological Immunofluorescent Images 査読

    Shinji Kitamura, Kensaku Takahashi, Yizhen Sang, Kazuhiko Fukushima, Kenji Tsuji, Jun Wada

    DIAGNOSTICS   10 ( 7 )   2020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)  

    DOI: 10.3390/diagnostics10070466

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  • The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway. 査読 国際誌

    Yoshiko Hada, Haruhito A Uchida, Nozomu Otaka, Yasuhiro Onishi, Shugo Okamoto, Mariko Nishiwaki, Rika Takemoto, Hidemi Takeuchi, Jun Wada

    International journal of molecular sciences   21 ( 12 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-β-galactosidase (SA-β-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H2O2 for an hour, then cultured in the absence or presence of 0.5-5.0 μM CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H2O2 treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway.

    DOI: 10.3390/ijms21124527

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  • Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury. 査読 国際誌

    Yizhen Sang, Kenji Tsuji, Akiko Inoue-Torii, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

    International journal of molecular sciences   21 ( 11 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury.

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  • Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study. 査読 国際誌

    Eri Katsuyama, Yoshia Miyawaki, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu-Asano, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Jun Wada

    BMC nephrology   21 ( 1 )   208 - 208   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). METHODS: In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. RESULTS: The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). CONCLUSION: As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

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  • Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury 査読

    Hiromasa Miyake, Katsuyuki Tanabe, Satoshi Tanimura, Yuri Nakashima, Tomoyo Morioka, Kana Masuda, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 ( 12 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms21124545

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  • The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway 査読

    Yoshiko Hada, Haruhito A. Uchida, Nozomu Otaka, Yasuhiro Onishi, Shugo Okamoto, Mariko Nishiwaki, Rika Takemoto, Hidemi Takeuchi, Jun Wada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 ( 12 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms21124527

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  • Risk Factors for Chronic Damage Accumulation Across Different Onset Eras in Systemic Lupus Erythematosus: A Cross-sectional Analysis of a Lupus Registry of Nationwide Institutions (LUNA) 査読

    Keiji Ohashi, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu Asano, Yoshia Miyawaki, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori-Watanabe, Tomoko Kawabata, Nobuyuki Yajima, Jun Wada

    ACTA MEDICA OKAYAMA   74 ( 3 )   191 - 198   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report 査読

    Yuriko Yamamura, Yoshinori Matsumoto, Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Toru Yamashita, Masahiro Yamamura, Ken-Ei Sada, Koji Abe, Jun Wada

    BMC PULMONARY MEDICINE   20 ( 1 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12890-020-01195-7

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  • Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury 査読

    Yizhen Sang, Kenji Tsuji, Akiko Inoue-Torii, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 ( 11 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms21114099

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  • Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice 査読

    Kazuhiko Fukushima, Shinji Kitamura, Kenji Tsuji, Yizhen Sang, Jun Wada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 ( 11 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms21114054

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  • Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials 査読

    Kaethe Goossen, Monika Becker, Mark R. Marshall, Stefanie Buehn, Jessica Breuing, Catherine A. Firanek, Simone Hess, Hisanori Nariai, James A. Sloand, Qiang Yao, Tae Ik Chang, JinBor Chen, Ramon Paniagua, Yuji Takatori, Jun Wada, Dawid Pieper

    AMERICAN JOURNAL OF KIDNEY DISEASES   75 ( 6 )   830 - 846   2020年6月

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  • Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case report 査読

    Katsuyuki Tanabe, Hiromitsu Kanzaki, Takahira Wada, Yuri Nakashima, Hitoshi Sugiyama, Hiroyuki Okada, Jun Wada

    MEDICINE   99 ( 21 )   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/MD.0000000000020464

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  • Targeting angiogenesis and lymphangiogenesis in kidney disease 査読

    Katsuyuki Tanabe, Jun Wada, Yasufumi Sato

    NATURE REVIEWS NEPHROLOGY   16 ( 5 )   289 - 303   2020年5月

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  • The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study 査読

    Akihiro Katayama, Atsuhito Tone, Mayu Watanabe, Sanae Teshigawara, Satoshi Miyamoto, Jun Eguchi, Atsuko Nakatsuka, Kenichi Shikata, Jun Wada

    DIABETOLOGY INTERNATIONAL   11 ( 2 )   97 - 104   2020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)  

    DOI: 10.1007/s13340-019-00408-7

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  • Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report 査読

    Natsumi Matsuoka, Kenji Tsuji, Eiki Ichihara, Takayuki Hara, Kazuhiko Fukushima, Kishio Toma, Shinji Kitamura, Kenichi Inagaki, Hitoshi Sugiyama, Jun Wada

    BMC NEPHROLOGY   21 ( 1 )   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12882-020-01775-z

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  • A novel homoplasmic mitochondrial DNA mutation (m.13376T>C, p.I347T) of MELAS presenting characteristic medial temporal lobe atrophy. 査読 国際誌

    Ryo Sasaki, Yasuyuki Ohta, Noriko Hatanaka, Koh Tadokoro, Emi Nomura, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yoshio Omote, Eisaku Morimoto, Sanae Teshigawara, Jun Wada, Yu-Ichi Goto, Koji Abe

    Journal of the neurological sciences   408   116460 - 116460   2020年1月

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  • Simultaneous development of IgA vasculitis and eosinophilic granulomatosis with polyangiitis. 査読 国際誌

    Yosuke Asano, Yoshinori Matsumoto, Tatsuhiko Miyazaki, Akihiro Ishizu, Shin Morizane, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken-Ei Sada, Hirofumi Makino, Jun Wada

    Modern rheumatology case reports   4 ( 1 )   63 - 69   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immunoglobulin A (IgA) vasculitis (IgAV) is a small vessel vasculitis presenting cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis caused by deposition of the IgA1-mediated immune complex. Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by eosinophil-rich and granulomatous inflammation in small to medium-sized vessels. Both IgAV and EGPA are classified as autoimmune systemic vasculitis, but the pathogenesis of immune complex-mediated IgAV and that of pauci-immune EGPA are different. Here we report a rare case of simultaneous development of IgAV and EGPA presenting palpable purpura and numbness in a patient with a history of asthma. Histological examination revealed leukocytoclastic vasculitis with deposition of IgA, IgM and C3 in the upper dermis and necrotising vasculitis with eosinophilic infiltration and granulomatous formation in the lower dermis and subcutaneous fat, indicating the existence of IgAV and EGPA. Our case provides evidence of concurrent development of two different types of vasculitis, which may affect disease-associated complications, therapeutic strategy and prognosis.

    DOI: 10.1080/24725625.2019.1673528

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  • Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome 査読

    Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Masashi Kitagawa, Keiko Tanaka, Yuzuki Kano, Koki Mise, Nozomu Otaka, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A. Uchida, Jun Wada

    PLOS ONE   15 ( 1 )   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0228337

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  • Conditions, pathogenesis, and progression of diabetic kidney disease and early decliner in Japan 査読

    Yui Yoshida, Kosuke Kashiwabara, Yosuke Hirakawa, Tetsuhiro Tanaka, Shinsuke Noso, Hiroshi Ikegami, Mitsuru Ohsugi, Kohjiro Ueki, Tomoya Mita, Hirotaka Watada, Daisuke Koya, Koki Mise, Jun Wada, Miho Shimizu, Takashi Wada, Yumi Ito, Ichiei Narita, Naoki Kashihara, Masaomi Nangaku, Yutaka Matsuyama

    BMJ OPEN DIABETES RESEARCH & CARE   8 ( 1 )   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/bmjdrc-2019-000902

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  • Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome. 査読 国際誌

    Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Masashi Kitagawa, Keiko Tanaka, Yuzuki Kano, Koki Mise, Nozomu Otaka, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A Uchida, Jun Wada

    PloS one   15 ( 1 )   e0228337   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS.

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  • Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr/lpr Mice. 査読 国際誌

    Sumie Hiramatsu-Asano, Katsue Sunahori-Watanabe, Sonia Zeggar, Eri Katsuyama, Tomoyuki Mukai, Yoshitaka Morita, Jun Wada

    Frontiers in immunology   11   616141 - 616141   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. Methods: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223 -/- Faslpr/lpr mice and the lupus phenotypes were analyzed. Results: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr /J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3' UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223 -/- Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8- cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223 +/+ Faslpr/lpr mice by flow cytometry. B6-Mir223 -/- Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. Conclusion: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.

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  • Damage accrual related to pregnancies before and after diagnosis of systemic lupus erythematosus: a cross-sectional and nested case-control analysis from a lupus registry 査読

    Morishita, M., Sada, K.-E., Ohashi, K., Miyawaki, Y., Asano, Y., Hayashi, K., Asano, S.H., Yamamura, Y., Watanabe, H., Narazaki, M., Matsumoto, Y., Kawabata, T., Yajima, N., Wada, J.

    Lupus   29 ( 2 )   2020年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/0961203319898766

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  • Robotic Renal Autotransplantation: A Feasibility Study in a Porcine Model 査読

    Risa Kubota, Motoo Araki, Koichiro Wada, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Yuichi Ariyoshi, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Yuzuki Kano, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    ACTA MEDICA OKAYAMA   74 ( 1 )   53 - 58   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Letter to the Editor (Case report) 査読

    Yuriko Yamamura, Yoshinori Matsumoto, Yosuke Asano, Yu Katayama, Keigo Hayashi, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Takano-Narazaki, Ken-Ei Sada, Jun Wada

    RHEUMATOLOGY ADVANCES IN PRACTICE   4 ( 1 )   2020年

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  • Immunomodulatory and regenerative effects of mesenchymal stem cell-derived extracellular vesicles in renal diseases

    Tsuji, K., Kitamura, S., Wada, J.

    International Journal of Molecular Sciences   21 ( 3 )   2020年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms21030756

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  • TREATMENT STATUS FOR OSTEOPOROSIS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: CROSS-SECTIONAL ANALYSIS FROM A LUPUS REGISTRY OF NATIONWIDE INSTITUTIONS (LUNA)

    Jun Wada

    Annals of the Rheumatic Diseases   2020年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/ANNRHEUMDIS-2020-EULAR.1202

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  • The Aging Population and Research into Treatments for Abdominal Aortic Aneurysms. 査読

    Ryoko Umebayashi, Haruhito Adam Uchida, Jun Wada

    Acta medica Okayama   73 ( 6 )   475 - 477   2019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)  

    Abdominal aortic aneurysms (AAAs) usually expand asymptomatically until the occurrence of a life-threatening event such as aortic rupture, which is closely associated with high mortality. AAA and aortic dissection are ranked among the top 10 causes of death in Japan. The major risk factors for AAA are age over 65 years, male gender, family history, and smoking. Thus, for prevention, smoking cessation is the most important lifestyle-intervention. For treatment, since AAA generally affects elderly people, less invasive treatment is preferable. However, the only established treatment for AAA is open repair and endovascular repair. This review describes potential medical treatments to slow aneurysm growth or prevent AAA rupture.

    DOI: 10.18926/AMO/57710

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  • HIV-associated Immune Complex Kidney Disease with C3-dominant Deposition Induced by HIV Infection after Treatment of IgA Nephropathy. 査読

    Chieko Kawakita, Masaru Kinomura, Nozomu Otaka, Masashi Kitagawa, Hitoshi Sugiyama, Nobuchika Kusano, Masashi Mizuno, Jun Wada

    Internal medicine (Tokyo, Japan)   58 ( 20 )   3001 - 3007   2019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)  

    A 57-year-old man was diagnosed with IgA nephropathy. Hematuria and proteinuria were improved by tonsillectomy plus methylprednisolone pulse therapy. Lymphadenopathy, hypocomplementemia and pancytopenia were observed six years later, and urinalysis abnormalities recurred. A biopsy revealed mesangial proliferative glomerulonephritis with C3-dominant deposition. Human immunodeficiency virus (HIV) antibody demonstrated positive conversion. He was diagnosed with HIV-associated immune complex kidney disease (HIVICK). The hematuria, proteinuria and hypocomplementemia were improved by reducing the HIV viral load through antiretroviral therapy. When C3-dominant deposition is observed on a renal biopsy, HIVICK must be differentiated.

    DOI: 10.2169/internalmedicine.2439-18

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  • Cluster Analysis Using Anti-Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis. 査読 国際誌

    Keiji Ohashi, Ken-Ei Sada, Yu Nakai, Shun Matsushima, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori Watanabe, Tomoko Kawabata, Jun Wada

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases   25 ( 6 )   246 - 251   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated. METHODS: Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters. RESULTS: Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2. CONCLUSIONS: Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.

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  • Impaired mental health status in patients with chronic kidney disease is associated with estimated glomerular filtration rate decline. 査読 国際誌

    Yasuhiro Onishi, Haruhito A Uchida, Hidemi Takeuchi, Yuki Kakio, Hitoshi Sugiyama, Jun Wada, Noriaki Shimada, Hironobu Tokumasu, Masaki Fukushima, Kenichiro Asano

    Nephrology (Carlton, Vic.)   24 ( 9 )   926 - 932   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Deteriorated health-related quality of life (HRQOL) is associated with increased risk for death in both chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients; however, the impact of HRQOL on CKD progression is not well investigated. METHODS: We aimed to evaluate the association between HRQOL and CKD progression in Japanese patients with CKD. One hundred and three outpatients who visited the department of nephrology at our hospital (mean estimated glomerular filtration rate (eGFR); 32.1 ± 11.2 mL/min per 1.73 m2 ) between April 2007 and March 2012 were enrolled in this study. The primary outcome was 30% decline of eGFR or ESRD. We assessed HRQOL of all participants at baseline, including the physical component summary (PCS), the mental component summary (MCS) and the role/social component summary (RCS), using SF-36. Based on the baseline score of PCS, MCS and RCS, we divided all subjects into two groups by median. RESULTS: We studied 66 men (64.1%) and 37 women aged 61.7 ± 10.0 years old. During approximately 2.5 years of follow-up period, 59 patients (57.3%) reached 30% eGFR decline or ESRD. Cox regression analyses demonstrated that lower MCS score was significantly associated with CKD progression (hazard ratio (HR) = 1.83, 95% CI = 1.04-3.21, P = 0.035), but that lower PCS score and RCS score were not (HR = 0.70, 95% CI = 0.39-1.25, P = 0.223; HR = 0.95, 95% CI = 0.54-1.67, P = 0.854, respectively). CONCLUSION: We found that impaired mental health was associated with CKD progression. The evaluation of the mental health should be performed in the patients with CKD.

    DOI: 10.1111/nep.13515

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  • Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model. 査読 国際誌

    Satoshi Tanimura, Katsuyuki Tanabe, Hiromasa Miyake, Kana Masuda, Keigo Tsushida, Tomoyo Morioka, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

    American journal of physiology. Renal physiology   317 ( 2 )   F264-F274 - F274   2019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)  

    Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/-) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/- mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/- mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

    DOI: 10.1152/ajprenal.00045.2019

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  • Development of Hypertrophic Pachymeningitis in a Patient With Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis With Polyangiitis. 査読 国際誌

    Yasuhiro Nakano, Yoshia Miyawaki, Ken-Ei Sada, Yuriko Yamamura, Yuzuki Kano, Keigo Hayashi, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Jun Wada

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases   25 ( 5 )   e61   2019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)  

    DOI: 10.1097/RHU.0000000000000694

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  • A Patient with Type 3 Autoimmune Polyglandular Syndrome who Developed Systemic Lupus Erythematosus 8 years after the Diagnosis of Autoimmune Hepatitis. 査読

    Tomoyo Mifune-Morioka, Haruhito A Uchida, Kazuhiko Fukushima, Mayu Watanabe, Chihiro Ouchi, Koki Mise, Chieko Kawakita, Yuzuki Kano, Akifumi Onishi, Kishio Toma, Jun Eguchi, Nozomu Wada, Fusao Ikeda, Erika Sasaki, Yu Suganami, Masayuki Kishida, Hitoshi Sugiyama, Hiroyuki Okada, Jun Wada

    Acta medica Okayama   73 ( 4 )   367 - 372   2019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)  

    Eight years prior to her present admission, a 61-year-old Japanese woman was diagnosed with autoimmune hepatitis, slowly progressive insulin-dependent diabetes mellitus, and chronic thyroiditis; she had been treated with oral prednisolone (PSL). After she suddenly discontinued PSL, she newly developed systemic lupus erythematosus. A combination therapy of oral PSL and intravenous cyclophosphamide resulted in remission. She was finally diagnosed with autoimmune polyglandular syndrome (APS) type 3 (3A ,3B, 3D), complicated with four different autoimmune diseases. Since patients with type 3 APS may present many manifestations over a long period of time, they should be carefully monitored.

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  • Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease. 査読

    Hironobu Toda, Haruhito Uchida, Kazufumi Nakamura, Hidemi Takeuchi, Masaru Kinomura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Jun Wada, Hiroshi Ito

    Internal medicine (Tokyo, Japan)   58 ( 13 )   1917 - 1922   2019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)  

    Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

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  • Capnocytophaga canimorsus peritonitis diagnosed by mass spectrometry in a diabetic patient undergoing peritoneal dialysis: a case report. 査読 国際誌

    Katsuyuki Tanabe, Shugo Okamoto, Sumie Hiramatsu Asano, Jun Wada

    BMC nephrology   20 ( 1 )   219 - 219   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Bacterial peritonitis is a serious complication of patients undergoing peritoneal dialysis (PD). Although the identification of causative organisms and use of appropriate antibiotics are essential for treatment, rare and fastidious bacteria are sometimes difficult to detect by conventional biochemical assays. Capnocytophaga canimorsus is a fastidious and slow-growing bacterium that forms a part of the normal oral flora of dogs and cats and is extremely rare as a peritonitis-causing organism. This report demonstrates the usefulness of a mass spectrometry-based technique in identifying such a rare organism in PD-related peritonitis and discusses the diagnosis and treatment of C. canimorsus peritonitis. CASE PRESENTATION: A 49-year-old woman with type 2 diabetes mellitus underwent PD for two years. Repeated exit-site infections led to subcutaneous pathway diversion two months ago. She was hospitalized with fever and abdominal pain as well as cloudy dialysis effluent. Laboratory data revealed increased serum C-reactive protein level and white blood cell (WBC) count in the effluent. Her exit site had no sign of infection, leading to the diagnosis of PD-related peritonitis. Initial therapy with intraperitoneal ceftazidime immediately ameliorated her symptoms, and the WBC count in the effluent normalized in five days. Culture test results of the dialysis effluent on admission were negative with no information regarding the infection route. However, mass spectrometry (MALDI Biotyper, Bruker Daltonics) successfully obtained the specific spectral pattern for C. canimorsus. She had four cats in her house and was advised not to allow the cats in the room where the bag exchange took place. CONCLUSIONS: C. canimorsus is a rare cause of peritonitis in PD patients and is usually susceptible to intraperitoneal third-generation cephalosporins. This mass spectrometry-based bacterial identification method could provide more opportunities to identify uncommon causes and promote appropriate antibiotics therapy in PD-related peritonitis.

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  • Cavernous Transformation and Granulomatous Epididymis in Behçet Disease 査読 国際誌

    Motokura Y, Watanabe H, Yamamura Y, Kano Y, Matsumoto Y, Kawabata T, Sada K. E, Wada J

    J Clin Rheumatol   25 ( 4 )   45 - 47   2019年6月

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  • Contrast-enhanced Computed Tomography-Guided Percutaneous Cryoablation of Renal Cell Carcinoma in a Renal Allograft: First Case in Asia. 査読

    Ichiro Tsuboi, Motoo Araki, Hiroyasu Fujiwara, Toshihiro Iguchi, Takao Hiraki, Naoko Arichi, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Tomoko Sako, Atsushi Takamoto, Koichiro Wada, Yasuyuki Kobayashi, Toyohiko Watanabe, Hiroyuki Yanai, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Hiroaki Shiina, Susumu Kanazawa, Yasutomo Nasu

    Acta medica Okayama   73 ( 3 )   269 - 272   2019年6月

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    記述言語:英語  

    Nephron-sparing treatment should be offered whenever possible to avoid dialysis in allograph cases. Cryoablation is a new treatment option for treating small-sized renal cell cancer (RCCs). We report a case of RCC arising in a kidney allograft treated by cryoablation. To our knowledge, this is the first case in Asia of RCC in a renal allograft treated using cryoablation. Contrast-enhanced CT-guided percutaneous renal needle biopsy and cryoablation were used to identify the RCC, which could not be identified by other techniques. The postoperative course was uneventful. Contrast-enhanced CT also showed no recurrence or metastases at the 6-month follow-up.

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  • Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet. 査読

    Tomonari Kimura, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Kaoru Akazawa, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Daiji Miura, Jun Wada, Hiroshi Ito

    International heart journal   60 ( 3 )   728 - 735   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-β1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of β-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

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  • The clinical efficacy of angiotensin II type1 receptor blockers on inflammatory markers in patients with hypertension: a multicenter randomized-controlled trial; MUSCAT-3 study. 査読 国際誌

    Ryoko Umebayashi, Haruhito A Uchida, Yuka Okuyama, Yuki Kakio, Yoshihisa Hanayama, Kenichi Shikata, Jun Wada

    Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals   24 ( 3 )   255 - 261   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Purpose: The purpose of present study was to evaluate the clinical efficacy of irbesartan on the anti-inflammatory and anti-oxidative stress effect in patients with hypertension compared to other ARBs. Further, we assessed the effect of the ARBs on kidney function and urinary albumin excretion. Methods: Eighty-five outpatients with hypertension who took an ARB except irbesartan more than 3 months were assigned into two groups, one continued the same ARB and the other switched the ARB to irbesartan for 6 months. Results: Although blood pressures were equally controlled (continue group: 148 ± 2/79 ± 2 mmHg to 131 ± 2/74 ± 2 mmHg; switch group: 152 ± 2/81 ± 2 mmHg to 132 ± 2/74 ± 2 mmHg; p < 0.001 each), the inflammatory markers (hsCRP, PTX3, MCP-1) and oxidative stress marker (MDA-LDL) did not change after 6 months in both groups. Urinary albumin excretion was significantly reduced only in the switch group without renal function deterioration (switch group 292.4 ± 857.9 mg/gCr to 250.6 ± 906.5 mg/gCr, p = 0.012). Conclusion: These results provide knowledge of the characteristics of irbesartan, suggesting appropriate choice of ARBs in the treatment for hypertension should be considered.

    DOI: 10.1080/1354750X.2018.1548033

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  • Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. 査読 国際誌

    Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Fumika Nanto-Hara, Jiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching-Chin Yang, Chitose Suzuki, Matthew C Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

    Nature communications   10 ( 1 )   1835 - 1835   2019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)   出版者・発行元:Nature Communications  

    Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

    DOI: 10.1038/s41467-019-09735-4

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  • Parathyroid Lipoadenoma: A Pitfall in Preoperative Localization. 査読

    Satoshi Fujisawa, Kenichi Inagaki, Jun Wada

    Internal medicine (Tokyo, Japan)   58 ( 8 )   1183 - 1184   2019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)  

    DOI: 10.2169/internalmedicine.1249-18

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  • Exogenous Vasohibin-2 Exacerbates Angiotensin II-Induced Ascending Aortic Dilation in Mice. 査読

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

    Circulation reports   1 ( 4 )   155 - 161   2019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)  

    Background: Chronic angiotensin II (AngII) infusion promotes ascending aortic dilation in C57BL/6J mice. Meanwhile, vasohibin-2 (VASH2) is an angiogenesis promoter in neovascularization under various pathologic conditions. The aim of this study was to investigate whether exogenous VASH2 influences chronic AngII-induced ascending aortic dilation. Methods and Results: Eight-ten-week-old male C57BL/6J mice were injected with adenovirus (Ad) expressing either VASH2 or LacZ. One week after the injection, mice were infused with either AngII or saline s.c. for 3 weeks. Mice were divided into 4 groups: AngII+VASH2, AngII+LacZ, saline+VASH2, and saline+LacZ. Overexpression of VASH2 significantly increased AngII-induced intimal areas as well as the external diameter of the ascending aorta. In addition, VASH2 overexpression promoted ascending aortic medial elastin fragmentation in AngII-infused mice, which was associated with increased matrix metalloproteinase activity and medial smooth muscle cell (SMC) apoptosis. On western blot analysis, accumulation of apoptotic signaling proteins, p21 and p53 was increased in the AngII+VASH2 group. Furthermore, transfection of human aortic SMC with Ad VASH2 increased p21 and p53 protein abundance upon AngII stimulation. Positive TUNEL staining was also detected in the same group of the human aortic SMC. Conclusions: Exogenous VASH2 exacerbates AngII-induced ascending aortic dilation in vivo, which is associated with increased medial apoptosis and elastin fragmentation.

    DOI: 10.1253/circrep.CR-19-0008

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  • The relationship between repeated measurement of casual and 24-h urinary sodium-to-potassium ratio in patients with chronic kidney disease. 査読 国際誌

    Yuka Okuyama, Haruhito A Uchida, Toshiyuki Iwahori, Hiroyoshi Segawa, Ayako Kato, Hidemi Takeuchi, Yuki Kakio, Ryoko Umebayashi, Masashi Kitagawa, Hitoshi Sugiyama, Katsuyuki Miura, Hirotsugu Ueshima, Jun Wada

    Journal of human hypertension   33 ( 4 )   286 - 297   2019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)  

    This study aimed to clarify the relationship between repeated measurements of casual (spot) and 24-h urinary sodium-to-potassium (Na/K) ratios in patients with chronic kidney disease (CKD). A total of 61 inpatients with CKD, 31 in stage 1-3 (eGFR [estimated glomerular filtration rate] ≥ 30 ml/min/1.73 m2) and 30 in stage 4-5 (eGFR < 30 ml/min/1.73 m2), aged 20-85 consuming a low-sodium diet (NaCl [sodium chloride] 6 g/day) were recruited. Urinary Na, K, and Na/K ratios were measured in both casual urine samples and 2-day, 24 h urine samples, and then analyzed by correlation and Bland-Altman analyses. Mean 24-h urine Na/K ratio was higher in participants in stage 4-5 (5.1) than in participants in stage 1-3 (4.1) CKD. Casual urine Na/K ratio was strongly correlated with 2-day, 24-h urine Na/K ratio by sampling 4 casual urine specimens every morning and evening in participants in stage 1-3 (r = 0.69-0.78), but not in stage 4-5 (r = 0.12-0.19). The bias for mean Na/K ratio between 2-day, 24-h urine, and the 4 casual urine sampling ranged from -0.86 to 0.16 in participants in stage 1-3, and the quality of agreement for the mean of this casual urine sampling was similar to that of sampling 8 casual urine samples for estimating 2-day, 24-h values. Methods using repeated casual urine Na/K ratios may provide a reasonable estimation of 24-h urine Na/K ratio in normotensive and hypertensive as well as individuals with stage 1-3, but not stage 4-5 CKD.

    DOI: 10.1038/s41371-018-0127-1

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  • Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells. 査読 国際誌

    Satoshi Fujisawa, Motoshi Komatsubara, Kanako Ogura-Ochi, Naoko Tsukamoto-Yamauchi, Kishio Toma, Kenichi Inagaki, Jun Wada, Fumio Otsuka

    Peptides   113   35 - 40   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The impact of orexins on anterior pituitary function has yet to be clarified. We studied the effects of orexin A and its interaction with the bone morphogenetic protein (BMP) system on the regulatory role of prolactin synthesis using rat lactotrope GH3 cells expressing BMP-4. Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells. Orexin A suppressed forskolin-induced, but not basal, prolactin mRNA expression without reducing cAMP levels. Of note, orexin A suppressed BMP-4-induced prolactin mRNA and cAMP synthesis. Impairment of the effects of orexin by chemical inhibitors suggested involvement of the P38 pathway in the OX1R activity that suppresses BMP-4-induced PRL expression. Given that inhibition of BMP-receptor signaling reduced prolactin mRNA levels, endogenous BMP action is likely to be linked to the activation of prolactin synthesis by GH3 cells. Orexin A was revealed to suppress Smad1/5/9 phosphorylation and Id-1 transcription induced by BMP-4, which was restored in the presence of orexin-receptor antagonists, suggesting that the inhibitory effect of orexin A occurred via OX1R. Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression. These results indicated that orexin A plays an inhibitory role in prolactin production through suppression of endogenous BMP activity in GH3 cells, suggesting that a new functional role of the interaction between orexin and BMP-4 is modulation of prolactin levels in lactotrope cells.

    DOI: 10.1016/j.peptides.2019.01.002

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  • Regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice derived CD4+ T cells. 査読 国際誌

    Sumie Hiramatsu, Katsue S Watanabe, Sonia Zeggar, Yosuke Asano, Yoshia Miyawaki, Yuriko Yamamura, Eri Katsuyama, Takayuki Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

    Scientific reports   9 ( 1 )   3054 - 3054   2019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)   出版者・発行元:Springer Nature  

    Global DNA hypomethylation in CD4+ cells in systemic lupus erythematosus (SLE) was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and Ctse mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was 93.3 ± 2.05% methylated in B6 mice, while 80.0 ± 6.2% methylated and mutated to CGGG in MRL mice. Kaiso is known to bind to mCGCG and we hypothesized that it represses expression of Ctse in B6 mice. The binding of Kaiso to mCGCG site in B6 mice was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or Trichostatin A showed the suppression of binding of Kaiso to mCGCG motif by ChIP-PCR and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.

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  • Effect of an enhanced recovery after surgery protocol in patients undergoing pancreaticoduodenectomy: A randomized controlled trial. 査読 国際誌

    Kosei Takagi, Ryuichi Yoshida, Takahito Yagi, Yuzo Umeda, Daisuke Nobuoka, Takashi Kuise, Shiro Hinotsu, Takashi Matsusaki, Hiroshi Morimatsu, Jun Eguchi, Jun Wada, Masuo Senda, Toshiyoshi Fujiwara

    Clinical nutrition (Edinburgh, Scotland)   38 ( 1 )   174 - 181   2019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 & AIMS: Evidence of the advantages of enhanced recovery after surgery (ERAS) protocols following pancreaticoduodenectomy (PD) is limited. The aim of this study was to examine the efficiency of ERAS protocols in patients following PD. METHODS: Between June 2014 and October 2016, patients undergoing PD were randomly assigned to receive ERAS protocols or standard care. The primary endpoint was the postoperative length of stay. Secondary endpoints included postoperative complications, postoperative quality-of-life (QoR-40J), readmission, and medical cost. RESULTS: Of 80 eligible patients, 74 were analyzed in intention-to-treat principles: 37 in the control group and 37 in the ERAS group. The mean length of stay in the ERAS group was significantly shorter than that in the control group (20.1 ± 5.4 vs 26.9 ± 13.5 days, P < 0.001). The ERAS group had a significantly lower percentage of postoperative complications (32.4% vs 56.8%, P = 0.034) and readmissions (0% vs 8.1%, P = 0.038). Quality-of-life was also significantly better in the ERAS group (184 ± 12.4 vs 177 ± 14.5, P = 0.022). The total medical cost was lower in the ERAS group, but not significantly ($25,445 ± 5065 vs $28,384 ± 9999, P = 0.085). CONCLUSIONS: The optimization of ERAS protocols in patients undergoing PD is safe and accelerates perioperative recovery and quality-of-life, thereby reducing the length of stay. Morbidity was significantly decreased in the ERAS group without compromising surgical outcome. REGISTRATION NUMBER: UMIN000014068.

    DOI: 10.1016/j.clnu.2018.01.002

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  • Risk factors for cytomegalovirus infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis. 査読 国際誌

    Michiko Morishita, Ken-Ei Sada, Yoshinori Matsumoto, Keigo Hayashi, Yosuke Asano, Sumie Hiramatsu Asano, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Haruki Watanabe, Tomoko Kawabata, Jun Wada

    PloS one   14 ( 7 )   e0218705   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Cytomegalovirus (CMV) infection under immunosuppression sometimes causes death. This study aimed to elucidate risk factors for CMV infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Patients with AAV who underwent remission induction treatment at Okayama University Hospital between 2006 and 2016 were retrospectively analyzed. The primary outcome was the development of CMV infection within 3 months. RESULTS: Of the 111 patients, 13 (11.7%) patients developed CMV infection. Patients with CMV infection were older (p = 0.030) and had a higher body mass index (p = 0.029) in comparison to those without CMV infection. A higher proportion had a severe form (p = 0.001) and granulomatosis with polyangiitis (GPA) (p = 0.001), as well as a higher Birmingham Vasculitis Activity Score (p = 0.018) and C-reactive protein (p = 0.018) levels at baseline. Using logistic regression analysis, severe form and GPA were independent risk factors (odds ratio [OR] = 9.68, 95% confidence interval [CI] = 1.92-60.23, and OR = 7.46, 95% CI = 1.46-47.60, respectively). In addition, patients with CMV infection were more likely than those without infection to be glucocorticoid-related diabetes mellitus (p = 0.025). CONCLUSION: Our study highlights disease severity and subgroups of AAV as risk factors for CMV infection.

    DOI: 10.1371/journal.pone.0218705

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  • Report of health checkup system for chronic kidney disease in general population in Okayama city: effect of health guidance intervention on chronic kidney disease outcome. 査読 国際誌

    Yuki Kakio, Haruhito A Uchida, Hidemi Takeuchi, Yuka Okuyama, Ryoko Umebayashi, Hiroyuki Watatani, Yohei Maeshima, Hitoshi Sugiyama, Jun Wada

    International journal of nephrology and renovascular disease   12   143 - 152   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: From 2011, Okayama municipal government started the health checkup follow-up project to find those who were unaware of suffering chronic kidney disease and to prevent from aggravation of CKD stage. In this study, we aimed to evaluate the effect of 2 years' CKD-follow-up project regarding renal function and CKD risks. Patients and methods: Those who received a health checkup by the national health insurance in Okayama city in 2011 were recruited. The patients with lifestyle-related diseases or metabolic syndrome were excluded. Subjects who had an estimated glomerular filtration rate<50 mL/min/1.73 m2 or urinary protein positive by dipstick test were defined as compromised renal function group. They were recommended to visit a medical institution. Non-compromised renal function participants with two or more risks for CKD (hyperglycemia, higher blood pressure, dyslipidemia, hyperuricemia) were recommended to receive a health guidance (risk group). The change of renal function and CKD risks between 2011 and 2013 in each group was examined. Results: A total of 28,309 people received a health checkup in 2011. In compromised renal function group, 39.5% (96/243) of the subjects improved their CKD stages in 2013 regardless of the visit of medical institutions or the frequency of receiving health checkup. In risk group, 63.4% (260/410) of the subjects decreased their CKD risks in 2013 independent of the reception of health guidance. Conclusion: In both compromised renal function group and risk group, more than half of subjects kept their kidney function (217/243) and decreased the number of CKD risks (260/410) in 2 years' follow-up. Receiving a health checkup itself and notification of one's own health condition could exert a protective effect on kidney function.

    DOI: 10.2147/IJNRD.S198781

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  • Thrombocytosis as a prognostic factor in polymyalgia rheumatica: characteristics determined from cluster analysis. 査読 国際誌

    Keigo Hayashi, Keiji Ohashi, Haruki Watanabe, Ken-Ei Sada, Kenta Shidahara, Yosuke Asano, Sumie Hiramatsu Asano, Yuriko Yamamura, Yoshia Miyawaki, Michiko Morishita, Yoshinori Matsumoto, Tomoko Kawabata, Jun Wada

    Therapeutic advances in musculoskeletal disease   11   1759720X19864822   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: This study aimed to identify the clinical subgroups of polymyalgia rheumatica (PMR) using cluster analysis and compare the outcomes among the identified subgroups. Methods: We enrolled patients with PMR who were diagnosed at Okayama University Hospital, Japan between 2006 and 2017, met the 2012 European League Against Rheumatism/American College of Rheumatology provisional classification criteria for PMR, and were treated with glucocorticoids. Hierarchical cluster analysis using variables selected by principal component analysis was performed to identify the clusters. Subsequently, the outcomes among the identified clusters were compared in the study. The primary outcome was treatment response at 1 month after commencement of treatment. The secondary outcome was refractory clinical course, which was defined as the requirement of additional treatments or relapse during a 2-year observational period. Results: A total of 61 consecutive patients with PMR were enrolled in the study. Their mean age was 71 years, and 67% were female. Hierarchical cluster analysis revealed three distinct subgroups: cluster 1 (n = 14) was characterized by patients with thrombocytosis (all patients showed a platelet count of >45 × 10⁴/µl), cluster 2 (n = 38), by patients without peripheral arthritis, and cluster 3 (n = 9), by patients with peripheral arthritis. The patients in cluster 1 achieved treatment response less frequently than those in cluster 2 (14% versus 47%, p = 0.030). Refractory cases were more frequent in cluster 1 than in cluster 2; however, no significant difference was noted (71% versus 42%, p = 0.06). Conclusions: Thrombocytosis could predict the clinical course in patients with PMR.

    DOI: 10.1177/1759720X19864822

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  • Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease. 査読 国際誌

    Akifumi Onishi, Hitoshi Sugiyama, Masashi Kitagawa, Toshio Yamanari, Keiko Tanaka, Ayu Ogawa-Akiyama, Yuzuki Kano, Koki Mise, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A Uchida, Jun Wada

    Disease markers   2019   5432453 - 5432453   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: Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2'-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD. Method: We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 years, male: 53.2%, and glomerulonephritis: 51.0%) using a competitive enzyme-linked immunosorbent assay and investigated the relationships among urine 5MedC, urine albumin, urine α1-microglobulin (α1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner. Results: The urine 5MedC level was significantly increased in the later stages of CKD compared to the early to middle stages of CKD. In multiple logistic regression models, urine 5MedC was significantly associated with the prediction of later CKD stages. Urine 5MedC (median value, 65.9 μmol/gCr) was significantly able to predict a 30% decline in the estimated GFR or a development of end-stage renal disease when combined with macroalbuminuria or an increased level of urine α1MG (median value, 5.7 mg/gCr). Conclusion: The present data demonstrate that the urine 5MedC level is associated with a reduced renal function and can serve as a novel and potent biomarker for predicting the renal outcome in CKD patients. Further studies will be necessary to elucidate the role of urine DNA methylation in the progression of CKD.

    DOI: 10.1155/2019/5432453

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  • Hemoptysis Originating from the Bronchial Artery in Takayasu Arteritis with Ulcerative Colitis

    Jun Wada

    Internal Medicine   2019年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/INTERNALMEDICINE.1463-18

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  • OPTIMAL INITIAL DOSE OF GLUCOCORTICOID FOR ELDERLY-ONSET ANCA ASSOCIATED VASCULITIS: SAFTY OUTOCOME ANALYSIS OF TWO NATIONWIDE, PROSPECTIVE, INCEPTION COHORT STUDIES

    Jun Wada

    Annals of the Rheumatic Diseases   2019年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/ANNRHEUMDIS-2019-EULAR.3420

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  • Exogenous Vasohibin-2 Influences Development of Angiotensin II-induced Ascending Aortic Aneurysms but Not Abdominal Aortic Aneurysms in Either Normolipidemic or Apolipoprotein E-Deficient Mice

    Jun Wada

    Arteriosclerosis, Thrombosis, and Vascular Biology   2019年

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    掲載種別:研究論文(学術雑誌)  

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  • DOSE-DEPENDENT RISK OF METHOTREXATE FOR RENAL IMPAIRMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Jun Wada

    Annals of the Rheumatic Diseases   2019年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/ANNRHEUMDIS-2019-EULAR.3422

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  • Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. 査読 国際誌

    Yusuke Shibata, Atsuko Nakatsuka, Jun Eguchi, Satoshi Miyamoto, Yukari Masuda, Motoharu Awazawa, Akinobu Takaki, Ryuichi Yoshida, Takahito Yagi, Jun Wada

    Journal of medical case reports   12 ( 1 )   368 - 368   2018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)  

    INTRODUCTION: Acquired partial lipoatrophy has been reported after bone marrow transplantation during childhood; however, no adult cases have previously been reported. We herein report two adult cases of acquired partial lipoatrophy after transplantation. CASE PRESENTATION: A 28-year-old Japanese woman developed diabetic ketoacidosis and received insulin therapy after bone marrow transplantation. She manifested partial lipoatrophy of the extremities, prominent insulin resistance, hyperglycemia, hypertriglyceridemia, and fatty liver. A 40-year-old Japanese woman underwent liver transplantation from a living donor for alcoholic liver disease after abstinence from alcohol. She newly developed non-alcoholic steatohepatitis and diabetes. Non-alcoholic steatohepatitis progressed to liver failure, and a second liver transplantation from a brain-dead donor was performed at 42 years of age. She demonstrated loss of subdermal fat of the upper and lower extremities, prominent insulin resistance, hyperglycemia, and hypertriglyceridemia. In both cases, the injection of recombinant methionyl human leptin reversed all of the metabolic abnormalities. CONCLUSIONS: Acquired partial lipoatrophy after transplantation is a manifestation of chronic graft-versus-host disease in adults. This entity is associated with diabetes with prominent insulin resistance and severe hypertriglycemia and can be successfully treated with metreleptin for the long term.

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  • Antineutrophil cytoplasmic antibody-positive familial Mediterranean fever and hyperthyroidism: A case report. 国際誌

    Sorato Segoe, Ken-Ei Sada, Keigo Hayashi, Yuriko Yamamura, Michiko Morishita, Haruki Watanabe, Yoshinori Matsumoto, Jun Wada

    Medicine   97 ( 51 )   e13805   2018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)  

    RATIONALE: Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder characterized by serositis and recurrent fever. Previous reports identified patients with antineutrophil cytoplasmic antibody (ANCA)-positive FMF, but vasculitis symptoms were not reported. PATIENT CONCERNS: We report the case of a 44-year-old man with numbness. He had a history of 3 episodes of pleurisy and was being treated with propylthiouracil for hyperthyroidism. Because he was ANCA-positive, we suspected drug-induced ANCA-associated vasculitis and propylthiouracil was discontinued. However, his numbness was not ameliorated, and he again developed high fever with pleurisy. DIAGNOSIS: Diagnosis of FMF was finally made, and genetic analysis revealed compound heterozygous mutations in exon 2 of the familial Mediterranean fever gene (L110P/E148Q). INTERVENTIONS: The patient was treated with 0.5 mg/day of colchicine. OUTCOMES: His numbness improved, and fever has not recurred. LESSONS: Appearance of ANCA and development of vasculitis should be considered in a clinical course of FMF with hyperthyroidism.

    DOI: 10.1097/MD.0000000000013805

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  • Diabetic nephropathy is associated with frailty in patients with chronic hemodialysis. 査読

    Yuki Kakio, Haruhito A Uchida, Hidemi Takeuchi, Yuka Okuyama, Michihiro Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Shingo Kasahara, Jun Wada

    Geriatrics & gerontology international   18 ( 12 )   1597 - 1602   2018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)  

    AIM: Since 1998, the leading cause of chronic hemodialysis in Japan has been diabetic nephropathy. Diabetes mellitus is known to be a risk factor for frailty, but it still remains unknown whether diabetic nephropathy is associated with frailty in chronic dialysis patients. The authors carried out the present study to reveal the association between frailty and diabetic nephropathy in chronic hemodialysis patients. METHODS: A total of 355 patients who were on hemodialysis were recruited. Participants were divided into two groups of either patients who suffered diabetic nephropathy with end-stage renal disease (DN group, n = 150) or not (Non-DN group, n = 205). The authors investigated the difference of the prevalence of frailty between the two groups. Furthermore, the authors examined the risk factors for frailty. RESULTS: The prevalence of frailty in the DN group was significantly higher than that in the Non-DN group (28.0% vs 16.5%, P = 0.0161). To evaluate the association between frailty and its risk factors, we compared frail patients (n = 71) and non-frail patients (n = 262). After adjusting their interrelationships by using multivariate logistic regression analysis, diabetic nephropathy was determined as a significant risk factor for frailty. CONCLUSIONS: The authors found the close association between frailty and diabetic nephropathy in chronic hemodialysis patients. Geriatr Gerontol Int 2018; 18: 1597-1602.

    DOI: 10.1111/ggi.13534

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    その他リンク: http://orcid.org/0000-0001-6508-4338

  • Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus 査読

    Miyawaki, Y., Sada, K., Asano, Y., Hayashi, K., Yamamura, Y., Hiramatsu, S., Ohashi, K., Morishita, M., Watanabe, H., Matsumoto, Y., Kawabata, T., Wada, J.

    Lupus   27 ( 13 )   2093   2018年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:{SAGE} Publications  

    DOI: 10.1177/0961203318804892

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  • An open-label pilot study on preventing glucocorticoid-induced diabetes mellitus with linagliptin. 査読 国際誌

    Yoshia Miyawaki, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Yoshinori Matsumoto, Katsue Sunahori-Watanabe, Tomoko Kawabata, Jun Wada

    Journal of medical case reports   12 ( 1 )   288 - 288   2018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)  

    BACKGROUND: Numerous patients develop diabetes in response to glucocorticoid therapy. This study explored the efficacy, safety, and preventive potential of the dipeptidyl peptidase-4 inhibitor, linagliptin (TRADJENTA®), in the development of glucocorticoid-induced diabetes mellitus. METHODS: From December 2014 to November 2015, we recruited non-diabetic Japanese patients scheduled for treatment with daily prednisolone ≥20 mg. Enrolled patients had at least one of following risk factors for glucocorticoid-induced diabetes mellitus: estimated glomerular filtration rate ≤ 60 mL/minute/1.73 m2; age ≥ 65 years; hemoglobin A1c > 6.0%. A daily dose of 5 mg of linagliptin was administered simultaneously with glucocorticoid therapy. The primary outcome was the development of glucocorticoid-induced diabetes mellitus. Additional orally administered hypoglycemic medications and/or insulin injection therapy was initiated according to the blood glucose level. RESULTS: Four of five patients developed glucocorticoid-induced diabetes mellitus within 1 week of glucocorticoid treatment. For 12 weeks, two of the four patients with glucocorticoid-induced diabetes mellitus required orally administered medications, but no patients required insulin. Blood glucose levels before breakfast and lunch tended to decrease with time; the median glucose levels before breakfast were 93 and 79.5 mg/dL at 1 and 3 weeks, respectively. Two patients experienced mild hypoglycemia around 2 weeks. Glucose levels after lunch remained high throughout all 4 weeks despite decreasing the glucocorticoid dosage. CONCLUSIONS: Linagliptin may be insufficient to prevent the development of glucocorticoid-induced diabetes mellitus but has the potential to reduce the requirement for insulin injection therapy. Treatment of glucocorticoid-induced diabetes mellitus was continued for at least 1 month and fasting hypoglycemia in early morning should be monitored after 2 weeks. TRIAL REGISTRATION: This trial was registered 02 November 2014 with UMIN Clinical Trials Registry (no. 000015588 ).

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  • Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy. 査読 国際誌

    Keiko Tanaka, Hitoshi Sugiyama, Toshio Yamanari, Koki Mise, Hiroshi Morinaga, Masashi Kitagawa, Akifumi Onishi, Ayu Ogawa-Akiyama, Katsuyuki Tanabe, Jun Eguchi, Yasukazu Ohmoto, Kenichi Shikata, Jun Wada

    Nephrology (Carlton, Vic.)   23 ( 9 )   855 - 862   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Trefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN). METHODS: We investigated the renal mRNA expression of TFF3 by real-time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively. RESULTS: The renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients. CONCLUSION: Renal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.

    DOI: 10.1111/nep.13444

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  • Chronic kidney disease is associated with carotid atherosclerosis and symptomatic ischaemic stroke. 査読 国際誌

    Nobuo Kajitani, Haruhito A Uchida, Isao Suminoe, Yuki Kakio, Masashi Kitagawa, Hajime Sato, Jun Wada

    The Journal of international medical research   46 ( 9 )   3873 - 3883   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective We aimed to investigate the relationships among chronic kidney disease (CKD), symptomatic ischaemic stroke, and carotid atherosclerosis. Methods We enrolled 455 patients who underwent carotid ultrasonography in our hospital, including 311 patients with symptomatic ischaemic stroke and 144 patients without symptomatic ischaemic stroke. Carotid intima-media thickness (IMT), the rate of internal carotid artery stenosis, and maximal plaque size were evaluated. Results The mean age of the patients was 68.5 ± 11.0 years and the mean estimated glomerular filtration rate (eGFR) was 68.8 ± 18.2 mL/min/1.73 m2. After adjustment for cardiovascular risk factors, the mean IMT was significantly higher in patients with CKD than in those without CKD. The IMT and eGFR were negatively correlated in patients with stroke (r = -0.169). Multiple logistic regression analyses showed that mean IMT, plaque size, and internal carotid artery stenosis were significant determinants of symptomatic ischaemic stroke after adjustment of multivariate risk factors. Furthermore, the eGFR was a negative determinant of symptomatic ischaemic stroke after adjusting for classical risk factors (odds ratio [95% confidence interval] = 0.868 [0.769-0.979]). Conclusion CKD might be associated with the carotid atherosclerosis and symptomatic ischaemic stroke.

    DOI: 10.1177/0300060518781619

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  • Peripheral artery disease is associated with frailty in chronic hemodialysis patients. 査読 国際誌

    Michihiro Okuyama, Hidemi Takeuchi, Haruhito A Uchida, Yuki Kakio, Yuka Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Shingo Kasahara, Jun Wada

    Vascular   26 ( 4 )   425 - 431   2018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)  

    Objectives The clinical condition of frailty is a common problem in the elderly population. However, the relationship between peripheral artery disease and frailty in hemodialysis patients remains unknown. The aim of this study was to identify the relationships between peripheral artery disease and frailty in Japanese chronic hemodialysis patients. Methods A total of 362 chronic hemodialysis patients who regularly visited six institutions were enrolled. To evaluate frailty, the modified Fried's frailty phenotype adjusted for Japanese were used. Peripheral artery disease was defined as ankle-brachial index <0.9. Results Of 362 patients, 62 patients (17.1%) were categorized as peripheral artery disease group and 300 patients (82.9%) as Non-peripheral artery disease group. The prevalence of frailty in the peripheral artery disease group was significantly higher than in the Non-peripheral artery disease group (34% vs. 18%, P = 0.0103). Non-shunt side grip strength was significantly stronger in the Non-peripheral artery disease group (23.6 kg vs. 17.0 kg, P < 0.0001). Thigh circumferences were also significantly larger in the Non-peripheral artery disease group (41.7 cm vs. 39.7 cm, P = 0.0054). A multivariate logistic regression analysis demonstrated that the factors independently associated with peripheral artery disease were as follows: frailty (odds ratio = 2.06, 95% confidence interval 1.09-3.89) and myocardial infarction (odds ratio = 3.74, 95% confidence interval 2.05-6.83). Conclusions It is concluded that peripheral artery disease is closely associated with frailty in hemodialysis patients.

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  • Identification of Novel Urinary Biomarkers for Predicting Renal Prognosis in Patients With Type 2 Diabetes by Glycan Profiling in a Multicenter Prospective Cohort Study: U-CARE Study 1. 査読 国際誌

    Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Sanae Teshigawara, Atsuhito Tone, Haruhito A Uchida, Jun Eguchi, Atsuko Nakatsuka, Daisuke Ogawa, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

    Diabetes care   41 ( 8 )   1765 - 1775   2018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)  

    OBJECTIVE: Because quantifying glycans with complex structures is technically challenging, little is known about the association of glycosylation profiles with the renal prognosis in diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: In 675 patients with type 2 diabetes, we assessed the baseline urinary glycan signals binding to 45 lectins with different specificities. The end point was a decrease of estimated glomerular filtration rate (eGFR) by ≥30% from baseline or dialysis for end-stage renal disease. RESULTS: During a median follow-up of 4.0 years, 63 patients reached the end point. Cox proportional hazards analysis revealed that urinary levels of glycans binding to six lectins were significantly associated with the outcome after adjustment for known indicators of DKD, although these urinary glycans, except that for DBA, were highly correlated with baseline albuminuria and eGFR. Hazard ratios for these lectins were (+1 SD for the glycan index) as follows: SNA (recognizing glycan Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 1.32 (1.04-1.67). Adding these glycan indexes to a model containing known indicators of progression improved prediction of the outcome (net reclassification improvement increased by 0.51 [0.22-0.80], relative integrated discrimination improvement increased by 0.18 [0.01-0.35], and the Akaike information criterion decreased from 296 to 287). CONCLUSIONS: The urinary glycan profile identified in this study may be useful for predicting renal prognosis in patients with type 2 diabetes. Additional investigation of glycosylation changes and urinary glycan excretion in DKD is needed.

    DOI: 10.2337/dc18-0030

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  • Refractory neuromyelitis optica spectrum disorder in systemic lupus erythematosus successfully treated with rituximab 査読

    K. Shidahara, K. Hayashi, K. E. Sada, S. Hiramatsu, M. Morishita, H. Watanabe, Y. Matsumoto, T. Kawabata, J. Wada

    Lupus   27 ( 8 )   1374 - 1377   2018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)   出版者・発行元:SAGE Publications Ltd  

    DOI: 10.1177/0961203318760994

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  • Role of Lgals9 Deficiency in Attenuating Nephritis and Arthritis in BALB/c Mice in a Pristane-Induced Lupus Model. 査読 国際誌

    Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada

    Arthritis & rheumatology (Hoboken, N.J.)   70 ( 7 )   1089 - 1101   2018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)  

    OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvement, the development of lupus nephritis determines prognosis, and arthritis impairs quality of life. Galectin 9 (Gal-9, Lgals9) is a β-galactoside-binding lectin that has been used for clinical application in autoimmune diseases, since recombinant Gal-9, as a ligand for T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), induces apoptosis of activated CD4+TIM-3+ Th1 cells. This study was undertaken to investigate whether deficiency of Lgals9 has beneficial or deleterious effects on lupus in a murine model. METHODS: Gal-9+/+ and Gal-9-/- female BALB/c mice were injected with pristane, and the severity of arthritis, proteinuria, and levels of autoantibody production were assessed at several time points immediately following injection. At 7 months after pristane injection, renal pathologic features, the severity of joint inflammation, and formation of lipogranulomas were evaluated. Subsets of inflammatory cells in the spleen and peritoneal lavage were characterized, and expression levels of cytokines from peritoneal macrophages were analyzed. RESULTS: Lgals9 deficiency protected against the development of immune complex glomerulonephritis, arthritis, and peritoneal lipogranuloma formation in BALB/c mice in this murine model of pristane-induced lupus. The populations of T cell subsets and B cells in the spleen and peritoneum were not altered by Lgals9 deficiency in pristane-injected BALB/c mice. Furthermore, Lgals9 deficiency protected against pristane-induced lupus without altering the Toll-like receptor 7-type I interferon pathway. CONCLUSION: Gal-9 is required for the induction and development of lupus nephritis and arthritis in this murine model of SLE. The results of the current investigation provide a potential new strategy in which antagonism of Gal-9 may be beneficial for the treatment of nephritis and arthritis in patients with SLE through targeting of activated macrophages.

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  • Development of a novel estimation method for hemoglobin A1c using glycated albumin in type 2 diabetes mellitus patients with end-stage renal disease. 査読

    Akihiko Nakamura, Ryo Kodera, Noriko Sakamoto, Haruyo Ujike, Jun Wada, Kenichi Shikata, Hirofumi Makino

    Diabetology international   9 ( 3 )   179 - 188   2018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)  

    Aim: We developed a novel estimation method for hemoglobin A1c (HbA1c) in type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). This method is based on the glycated albumin (GA) level. Methods: Of the 788 Japanese patients with T2D included in this study, 545 had normal renal function (NRF group) and 243 had ESRD. Oral glucose tolerance tests (OGTTs) were performed in 80 subjects. The variables GA, body mass index (BMI), hemoglobin (Hb), and estimated glomerular filtration rate (eGFR) were significantly associated with the GA-to-HbA1c ratio and were used to determine the estimated HbA1c (eHbA1c). One method of estimating HbA1c involved dividing GA by the GA-to-HbA1c ratio predicted from the estimated regression equation; the estimated HbA1c obtained in this manner was denoted eHbA1c-1. Results: eHbA1c-1 (%) = GA × [4.688 - 18.833 × GA-1 - 0.015 × BMI - 0.037 × Hb (- 0.002 × eGFR for patients without ESRD)]-1; adjusted R 2 = 0.676 for actual HbA1c. The sensitivity of eHbA1c-1 was better than that of GA for diabetes diagnosis using the 75-g OGTT. There were no differences in the slope of eHbA1c-1 versus GA and the variance of eHbA1c-1 between the ESRD and NRF groups. eHbA1c-1 was not associated with Hb, erythropoiesis-stimulating agent use, or ESRD concomitance. Conclusions: eHbA1c-1 may be a useful parameter for estimating HbA1c in T2D patients with ESRD.

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  • Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression. 査読 国際誌

    Katsuyuki Tanabe, Yasufumi Sato, Jun Wada

    International journal of molecular sciences   19 ( 7 )   1859   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chronic kidney disease (CKD) is a major global health problem. Unless intensive intervention is initiated, some patients can rapidly progress to end-stage kidney disease. However, it is often difficult to predict renal outcomes using conventional laboratory tests in individuals with CKD. Therefore, many researchers have been searching for novel biomarkers to predict the progression of CKD. Angiogenesis is involved in physiological and pathological processes in the kidney and is regulated by the balance between a proangiogenic factor, vascular endothelial growth factor (VEGF)-A, and various endogenous antiangiogenic factors. In recent reports using genetically engineered mice, the roles of these antiangiogenic factors in the pathogenesis of kidney disease have become increasingly clear. In addition, recent clinical studies have demonstrated associations between circulating levels of antiangiogenic factors and renal dysfunction in CKD patients. In this review, we summarize recent advances in the study of representative endogenous antiangiogenic factors, including soluble fms-related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor, VEGF-A165b, endostatin, and vasohibin-1, in associations with kidney diseases and discuss their predictive potentials as biomarkers of progression of CKD.

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  • Rationale and study design of a clinical trial to assess the effects of LDL apheresis on proteinuria in diabetic patients with severe proteinuria and dyslipidemia 査読

    Takashi Wada, Eri Muso, Shoichi Maruyama, Akinori Hara, Kengo Furuichi, Kenichi Yoshimura, Mariko Miyazaki, Eiichi Sato, Masanori Abe, Yugo Shibagaki, Ichiei Narita, Hitoshi Yokoyama, Noriko Mori, Yukio Yuzawa, Takeshi Matsubara, Tatsuo Tsukamoto, Jun Wada, Takafumi Ito, Kosuke Masutani, Kazuhiko Tsuruya, Shoichi Fujimoto, Akihiro Tsuda, Hitoshi Suzuki, Kenji Kasuno, Yoshio Terada, Takeshi Nakata, Noriaki Iino, Shuzo Kobayashi

    Clinical and Experimental Nephrology   22 ( 3 )   591 - 596   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    DOI: 10.1007/s10157-017-1488-4

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  • IgA Nephropathy Complicated with X-linked Thrombocytopenia. 査読

    Yuki Kakio, Haruhito Adam Uchida, Masashi Kitagawa, Yuka Arata, Ayako Kato, Akiko Inoue-Torii, Norikazu Hinamoto, Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Jun Wada

    Acta medica Okayama   72 ( 3 )   301 - 307   2018年6月

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    記述言語:英語  

    Renal involvement is occasionally observed in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). It has been reported that galactose-deficient IgA is a closely linked to IgA nephropathy (IgAN), suggesting that patients with XLT/WAS associated with reduced galactosylation on serum IgA are susceptible to IgAN. It is necessary to pay more attention to patients with IgAN due to the potential complication with XLT/WAS. We here present a patient of XLT complicated with mild IgAN who underwent tonsillectomy combined with steroid pulse therapy to achieve complete clinical remission.

    DOI: 10.18926/AMO/56077

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  • Estrogen-related receptor α is essential for maintaining mitochondrial integrity in cisplatin-induced acute kidney injury 査読 国際誌

    Tsushida K, Tanabe K, Masuda K, Tanimura S, Miyake H, Arata Y, Sugiyama H, Wada J

    Biochem Biophys Res Commun   498 ( 4 )   918 - 924   2018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)  

    DOI: 10.1016/j.bbrc.2018.03.080

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  • Incretins modulate progesterone biosynthesis by regulating bone morphogenetic protein activity in rat granulosa cells 査読

    Yuki Nishiyama, Toru Hasegawa, Shiho Fujita, Nahoko Iwata, Satoko Nagao, Takeshi Hosoya, Kenichi Inagaki, Jun Wada, Fumio Otsuka

    Journal of Steroid Biochemistry and Molecular Biology   178   82 - 88   2018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)   出版者・発行元:Elsevier Ltd  

    DOI: 10.1016/j.jsbmb.2017.11.004

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  • Cilostazol Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysms but Not Atherosclerosis in Apolipoprotein E-Deficient Mice. 査読 国際誌

    Ryoko Umebayashi, Haruhito A Uchida, Yuki Kakio, Venkateswaran Subramanian, Alan Daugherty, Jun Wada

    Arteriosclerosis, thrombosis, and vascular biology   38 ( 4 )   903 - 912   2018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)   出版者・発行元:Lippincott Williams and Wilkins  

    DOI: 10.1161/ATVBAHA.117.309707

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  • The Prevalence of Frailty and its Associated Factors in Japanese Hemodialysis Patients. 査読 国際誌

    Hidemi Takeuchi, Haruhito A Uchida, Yuki Kakio, Yuka Okuyama, Michihiro Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Jun Wada

    Aging and disease   9 ( 2 )   192 - 207   2018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)  

    The population undergoing dialysis is aging worldwide, particularly in Japan. The clinical condition of frailty is the most problematic expression in the elderly population. Potential pathophysiological factors of frailty present in patients with CKD and are accentuated in patients with ESRD. The aim of this study was to identify the prevalence and predictors of frailty in Japanese HD patients. This study was a multicenter, cross-sectional and observational investigation conducted at 6 institutions. To evaluate frailty, the modified Fried's frailty phenotype adjusted for Japanese as the self-reported questionnaire was used. Of the 542 patients visiting each institution, 388 were enrolled in this study. In total, 26.0% of participants were categorized as not-frailty, 52.6% as pre-frailty and 21.4% as frailty. The prevalence of frailty increased steadily with age and was more prevalent in females than in males and the subjects with frailty received polypharmacy. A multivariate logistic regression analysis revealed that the factors independently associated with frailty were the following: female gender (odds ratio [OR] = 3.661, 95% confidence interval [CI] 1.398-9.588), age (OR = 1.065, 95% CI 1.014-1.119), age ≥ 75 years old (OR = 4.892, 95% CI 1.715-13.955), body mass index (BMI) < 18.5 (OR = 0.110, 95% CI 0.0293-0.416), number of medications being taken (OR = 1.351, 95% CI 1.163-1.570), diabetes mellitus (DM) (OR = 2.765, 95% CI 1.081-7.071) and MNA-SF ≤ 11 (OR = 7.405, 95% CI 2.732-20.072). Frailty was associated with the accumulation of risk factors. The prevalence of frailty in Japanese patients with HD was relatively lower than that previously reported in Western developed countries; however, it was extremely high compared to the general population regardless of age. Our findings suggest that frailty might be associated with an increase in the prevalence of adverse health outcomes in patients with HD.

    DOI: 10.14336/AD.2017.0429

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  • The KCNQ1 gene polymorphism as a shared genetic risk for rheumatoid arthritis and chronic periodontitis in Japanese adults: A pilot case-control study. 査読 国際誌

    Tetsuo Kobayashi, Jun-Ichi Kido, Yuichi Ishihara, Kazuhiro Omori, Satoshi Ito, Takato Matsuura, Takashi Bando, Jun Wada, Akira Murasawa, Kiyoshi Nakazono, Akio Mitani, Shogo Takashiba, Toshihiko Nagata, Hiromasa Yoshie

    Journal of periodontology   89 ( 3 )   315 - 324   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: A number of studies have suggested a bidirectional relationship of periodontitis with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). However, the genetic factors that underlie these relationships have not been elucidated. METHODS: We conducted a multicenter case-control study that included 185 patients with RA and chronic periodontitis (CP), 149 patients with T2DM and CP, 251 patients with CP, and 130 systemically and periodontally healthy controls from a cohort of Japanese adults to assess the shared genetic risk factors for RA and CP as well as for T2DM and CP. A total of 17 candidate single nucleotide polymorphisms (SNPs) associated with RA, T2DM, and CP were genotyped. RESULTS: Multiple logistic regression analyses revealed that the KCNQ1 rs2237892 was significantly associated with comorbidity of RA and CP (P = 0.005) after adjustment for age, sex, and smoking status. The carriers of the T allele among patients with RA and CP showed significantly higher disease activity scores including 28 joints using C-reactive protein values than the non-carriers (P = 0.02), although the age, female percentage, and smoking status were comparable. Other SNPs were not associated with comorbidity of RA and CP, T2DM and CP, or susceptibility to CP. CONCLUSION: The results of the present pilot study suggest for the first time that the KCNQ1 rs2237892 may constitute a shared genetic risk factor for RA and CP, but not for T2DM and CP in Japanese adults.

    DOI: 10.1002/JPER.17-0412

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  • High calcium enhances the expression of double-stranded RNA sensors and antiviral activity in epidermal keratinocytes 査読

    Yuriko Yamamura, Shin Morizane, Takenobu Yamamoto, Jun Wada, Keiji Iwatsuki

    Experimental Dermatology   27 ( 2 )   129 - 134   2018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)   出版者・発行元:Blackwell Publishing Ltd  

    DOI: 10.1111/exd.13456

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    その他リンク: http://orcid.org/0000-0003-1468-5170

  • Anti-SS-A/Ro antibody positivity as a risk factor for relapse in patients with polymyositis/dermatomyositis. 査読 国際誌

    Noriko Tatebe, Ken-Ei Sada, Yosuke Asano, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Mariko Narazaki, Katsue Watanabe, Tomoko Kawabata, Jun Wada

    Modern rheumatology   28 ( 1 )   141 - 146   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The objective of this study is to elucidate predictors of relapse in patients with polymyositis and dermatomyositis (PM/DM). METHODS: Fifty PM/DM patients who achieved disease stabilization at Okayama University Hospital in 2004-2014 were enrolled retrospectively. Candidate predictors such as demographic factors, clinical symptoms, laboratory data, and treatment status were compared. RESULTS: The mean age of enrolled patients was 58 years; 34 were female. The patient groupings were as follows: 21 with PM, 27 with DM, and two with clinically amyopathic DM. During a mean observation period of 685 d, 5 patients (10%) died and 20 (40%) relapsed. The relapsed patients displayed baseline muscle weakness less frequently (85% versus 100%, p = .03) and anti-SS-A/Ro antibody more frequently (65% versus 27%, p = .007). Anti-SS-A/Ro-positive patients exhibited a higher relapse rate than anti-SS-A/Ro-negative patients (log-rank test, p = .03). Anti-SS-A/Ro-positive patients also exhibited higher anti-Jo-1 antibody positivity and lower levels of serum complement. After adjusting anti-Jo-1 antibody positivity, age, sex, CK <500 IU/L, and lung involvement, anti-SS-A/Ro positivity was still an independent risk factor for higher relapse-rate (odds ratio, 5.5; 95% confidence interval, 1.4-25.1). CONCLUSIONS: Anti-SS-A/Ro antibody positivity may be a useful biomarker for prediction of relapse.

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  • Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease. 査読 国際誌

    Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Masashi Kitagawa, Keiko Tanaka, Akifumi Onishi, Toshio Yamanari, Hiroshi Morinaga, Haruhito Adam Uchida, Kazufumi Nakamura, Hiroshi Ito, Jun Wada

    PloS one   13 ( 3 )   e0193695   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science  

    DOI: 10.1371/journal.pone.0193695

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  • Impact of nocturnal blood pressure variability on renal arterioles 査読 国際誌

    Uchida H. A, Kitagawa M, Wada J

    Hypertens Res   41 ( 1 )   6 - 7   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/hr.2017.88

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  • Deletion of pro-angiogenic factor vasohibin-2 ameliorates glomerular alterations in a mouse diabetic nephropathy model. 査読 国際誌

    Kana Masuda, Katsuyuki Tanabe, Haruyo Ujike, Norikazu Hinamoto, Hiromasa Miyake, Satoshi Tanimura, Hitoshi Sugiyama, Yasufumi Sato, Yohei Maeshima, Jun Wada

    PloS one   13 ( 4 )   e0195779   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Angiogenesis has been implicated in glomerular alterations in the early stage of diabetic nephropathy. We previously reported the renoprotective effects of vasohibin-1 (VASH1), which is a novel angiogenesis inhibitor derived from endothelial cells, on diabetic nephropathy progression. Vasohibin-2 (VASH2) was originally identified as a VASH1 homolog and possesses pro-angiogenic activity in contrast to VASH1. In addition, VASH2 was recently shown to promote epithelial-to-mesenchymal transition via enhanced transforming growth factor (TGF)-β signaling in cancer cells. Herein, we investigated the pathogenic roles of VASH2 in diabetic nephropathy using VAHS2-deficient mice. The type 1 diabetes model was induced by intraperitoneal injections of streptozotocin in VASH2 homozygous knockout (VASH2LacZ/LacZ) or wild-type mice. These mice were euthanized 16 weeks after inducing hyperglycemia. Increased urine albumin excretion and creatinine clearance observed in diabetic wild-type mice were significantly prevented in diabetic VASH2-deficient mice. Accordingly, diabetes-induced increase in glomerular volume and reduction in glomerular slit-diaphragm density were significantly improved in VASH2 knockout mice. Increased glomerular endothelial area was also suppressed in VASH2-deficient mice, in association with inhibition of enhanced vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), but not VEGF level. Furthermore, glomerular accumulation of mesangial matrix, including type IV collagen, and increased expression of TGF-β were improved in diabetic VASH2 knockout mice compared with diabetic wild-type mice. Based on the immunofluorescence findings, endogenous VASH2 localization in glomeruli was consistent with mesangial cells. Human mesangial cells (HMCs) were cultured under high glucose condition in in vitro experiments. Transfection of VASH2 small interfering RNA (siRNA) into the HMCs resulted in the suppression of type IV collagen production induced by high glucose compared with control siRNA. These results indicate that VASH2 may be involved in diabetes-induced glomerular alterations, particularly impaired filtration barrier and mesangial expansion. Therefore, VASH2 is likely to represent a promising therapeutic target for diabetic nephropathy.

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  • Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease. 査読 国際誌

    Toshio Yamanari, Hitoshi Sugiyama, Keiko Tanaka, Hiroshi Morinaga, Masashi Kitagawa, Akifumi Onishi, Ayu Ogawa-Akiyama, Yuzuki Kano, Koki Mise, Yasukazu Ohmoto, Kenichi Shikata, Jun Wada

    BioMed research international   2018   3024698 - 3024698   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Introduction: Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods: We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m2). Results: The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion: The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

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  • Olmesartan ameliorates hepatic insufficiency and serum TGF-β1 level in hypertensive patients with non-alcoholic fatty liver disease 査読

    Nozomu Otaka, Haruhito A. Uchida, Ryoko Umebayashi, Yasuhiro Onishi, Yuka Okuyama, Hidemi Takeuchi, Yuki Kakio, Hitoshi Sugiyama, Fumio Kondo, Kazushi Harada, Hisanao Norii, Yuko Okazaki, Taro Sugimoto, Hiroo Hashimoto, Jun Wada

    Therapeutic Research   39 ( 2 )   159 - 166   2018年

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    掲載種別:研究論文(学術雑誌)  

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  • Correction: Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus−Derived T Cells (Journal of Immunology (2017) 198 (4268-4276) DOI: 10.4049/jimmunol.1601705)

    Katsuyama, E., Yan, M., Watanabe, K.S., Narazaki, M., Matsushima, S., Yamamura, Y., Hiramatsu, S., Ohashi, K., Watanabe, H., Katsuyama, T., Zeggar, S., Yoshida, N., Moulton, V.R., Tsokos, G.C., Sada, K.-E., Wada, J.

    Journal of Immunology   201 ( 3 )   1104 - 1104   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.4049/jimmunol.1800810

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  • Cardiovocal syndrome (Ortner syndrome) associated with secondary pulmonary arterial hypertension in a patient with mixed connective tissue disease

    Jun Wada

    Modern Rheumatology Case Reports   2 ( 1 )   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/24725625.2017.1368436

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  • Secretomes from Mesenchymal Stem Cells against Acute Kidney Injury: Possible Heterogeneity

    Jun Wada

    Stem Cells International   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2018/8693137

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  • Perplexing role of galectin 9 in experimental lupus models: comment on the article by Zeggar et al Reply

    Jun Wada

    Arthritis & Rheumatology   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/ART.40563

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  • TREATMENT RESPONSE AS A PREDICTOR FOR REFRACTORY DISEASE AND/OR TRANSITION TO RHEUMATOID ARTHRITIS IN PATIENTS WITH POLYMYALGIA RHEUMATICA

    Jun Wada

    Annals of the Rheumatic Diseases   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/ANNRHEUMDIS-2018-EULAR.1895

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  • Primary peritoneal carcinosarcoma in a dialysis patient 査読

    Keiko Tanaka, Katsuyuki Tanabe, Naoko Nishii, Kana Masuda, Yuka Arata, Akifumi Ohnishi, Masaru Kinomura, Hitoshi Sugiyama, Jun Wada

    NEPHROLOGY   22 ( 11 )   925 - 925   2017年11月

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  • The effects of non-surgical periodontal treatment on glycemic control, oxidative stress balance and quality of life in patients with type 2 diabetes: A randomized clinical trial 査読

    Hirofumi Mizuno, Daisuke Ekuni, Takayuki Maruyama, Kota Kataoka, Toshiki Yoneda, Daiki Fukuhara, Yoshio Sugiura, Takaaki Tomofuji, Jun Wada, Manabu Morita

    PLOS ONE   12 ( 11 )   e0188171   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0188171

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  • Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who Was Unable to Continue Anti-TNF Therapy 査読

    Eri Katsuyama, Hiroshi Wakabayashi, Ken-ei Sada, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Mariko Narazaki, Noriko Tatebe, Katsue S. Watanabe, Tomoko Kawabata, Jun Wada

    ACTA MEDICA OKAYAMA   71 ( 5 )   445 - 448   2017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)  

    DOI: 10.18926/AMO/55444

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  • Immunohistochemistry of Vasohibin-2 in Human Kidney Disease: Implications in Impaired Glucose Tolerance and Reduced Renal Function 査読

    Yuka Arata, Katsuyuki Tanabe, Norikazu Hinamoto, Hiroko Yamasaki, Hitoshi Sugiyama, Yohei Maeshima, Naoki Kanomata, Yasufumi Sato, Jun Wada

    ACTA MEDICA OKAYAMA   71 ( 5 )   369 - 380   2017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)  

    DOI: 10.18926/AMO/55434

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  • Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice 査読

    Haruki Watanabe, Katsue S. Watanabe, Keyue Liu, Sumie Hiramatsu, Sonia Zeggar, Eri Katsuyama, Noriko Tatebe, Akiya Akahoshi, Fumiaki Takenaka, Takahisa Hanada, Masaru Akehi, Takanori Sasaki, Ken-ei Sada, Eiji Matsuura, Masahiro Nishibori, Jun Wada

    MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT   6   31 - 39   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.omtm.2017.05.006

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  • Reprogramming of metabolism in immune-mediated cells 査読

    Jun Wada

    Diabetology International   8 ( 3 )   244 - 247   2017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)   出版者・発行元:Springer Tokyo  

    DOI: 10.1007/s13340-017-0321-3

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  • Paratubular basement membrane insudative lesions predict renal prognosis in patients with type 2 diabetes and biopsy-proven diabetic nephropathy 査読

    Koki Mise, Yutaka Yamaguchi, Junichi Hoshino, Toshiharu Ueno, Akinari Sekine, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Takeshi Fujii, Shigeko Hara, Hitoshi Sugiyama, Hirofumi Makino, Jun Wada, Kenichi Ohashi, Kenmei Takaichi, Yoshifumi Ubara

    PLOS ONE   12 ( 8 )   e0183190   2017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)  

    DOI: 10.1371/journal.pone.0183190

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  • Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells 査読

    Kanako Ogura-Ochi, Satoshi Fujisawa, Nahoko Iwata, Motoshi Komatsubara, Yuki Nishiyama, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Jun Wada, Fumio Otsuka

    PEPTIDES   94   19 - 24   2017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)  

    DOI: 10.1016/j.peptides.2017.06.001

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  • Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells 査読

    Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R. Moulton, George C. Tsokos, Ken-Ei Sada, Jun Wada

    JOURNAL OF IMMUNOLOGY   198 ( 11 )   4268 - 4276   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4049/jimmunol.1601705

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    その他リンク: http://orcid.org/0000-0003-1468-5170

  • Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis 査読

    Koki Mise, Toshiharu Ueno, Junichi Hoshino, Ryo Hazue, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Takeshi Fujii, Shigeko Hara, Jun Wada, Hirofumi Makino, Kenmei Takaichi, Kenichi Ohashi, Yoshifumi Ubara

    DIABETES RESEARCH AND CLINICAL PRACTICE   127   187 - 197   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.diabres.2017.03.006

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    その他リンク: http://orcid.org/0000-0003-1468-5170

  • A retrospective observational study of glucocorticoid-induced diabetes mellitus with IgA nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy 査読

    Yoshia Miyawaki, Takayuki Katsuyama, Ken-Ei Sada, Sumie Hiramatsu, Keiji Ohashi, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Tatsuyuki Inoue, Masaru Kinomura, Hitoshi Sugiyama, Jun Wada

    PLOS ONE   12 ( 5 )   e0178018   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0178018

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  • Practical efficacy of olmesartan versus azilsartan in patients with hypertension: a multicenter randomized-controlled trial (MUSCAT-4 study) 査読

    Yuki Kakio, Haruhito A. Uchida, Ryoko Umebayashi, Hidemi Takeuchi, Yuka Okuyama, Yoshihisa Hanayama, Jun Wada

    BLOOD PRESSURE MONITORING   22 ( 2 )   59 - 67   2017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)  

    DOI: 10.1097/MBP.0000000000000229

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  • Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions 査読

    Motoshi Komatsubara, Takayuki Hara, Takeshi Hosoya, Kishio Toma, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Kenichi Inagaki, Jun Wada, Fumio Otsuka

    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY   165 ( Pt B )   182 - 189   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jsbmb.2016.06.002

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  • Salt and sugar: Bad company 査読

    Jun Wada

    JOURNAL OF DIABETES INVESTIGATION   8 ( 1 )   32 - 33   2017年1月

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  • Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease 査読

    Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuhiro Nouso, Atsuko Nakatsuka, Jun Wada, Kazuko Koike, Koji Miyahara, Hidenori Shiraha, Kazuhide Yamamoto, Hiroyuki Okada

    HEPATOLOGY INTERNATIONAL   11 ( 1 )   115 - 124   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12072-016-9773-y

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  • The level of urinary semaphorin3A is associated with disease activity in patients with minimal change nephrotic syndrome. 査読 国際誌

    Akiko Inoue-Torii, Shinji Kitamura, Jun Wada, Kenji Tsuji, Hirofumi Makino

    International journal of nephrology and renovascular disease   10   167 - 174   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Semaphorin3A is a secreted protein known to be involved in organogenesis, immune responses and cancer. In the kidney, semaphorin3A is expressed in the glomerular podocytes, distal tubules and collecting tubules, and believed to play a role in the regulation of the kidney development and function. We examined the serum and urinary semaphorin3A levels in 72 patients with renal disease and 5 healthy volunteers. The patients had been diagnosed with thin basement membrane disease (n=4), minimal change nephrotic syndrome (MCNS; n=22), IgA nephritis (n=21), membranous nephropathy (n=16) and focal segmental glomerular sclerosis (n=9). The level of urinary semaphorin3A in MCNS patients tended to be relatively high among all disease groups. We also investigated the urinary semaphorin3A level in 7 patients with MCNS from disease onset to remission during the drug therapy. MCNS patients in pre-remission states had higher urinary semaphorin3A levels than those in post-remission states receiving immunosuppressive therapies. These results suggested that the urinary semaphorin3A level correlates with the MCNS activity. Semaphorin3A has the potential as a biomarker for MCNS to clarify the reactivity for therapy and may be useful in examining other glomerular diseases with proteinuria as well.

    DOI: 10.2147/IJNRD.S132980

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  • Sustained Tubulointerstitial Inflammation in Kidney with Severe Leptospirosis 査読

    Keiko Tanaka, Katsuyuki Tanabe, Naoko Nishii, Keiichi Takiue, Hitoshi Sugiyama, Jun Wada

    INTERNAL MEDICINE   56 ( 10 )   1179 - 1184   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.56.8084

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  • The Successful Treatment of Refractory Polyarteritis Nodosa Using Infliximab 査読

    Satoko Matsuo, Keigo Hayashi, Eisaku Morimoto, Ayako Kato, Ken-Ei Sada, Haruki Watanabe, Mariko Takano-Narazaki, Katsue Sunahori-Watanabe, Tomoko Kawabata, Jun Wada

    INTERNAL MEDICINE   56 ( 11 )   1435 - 1438   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.56.8235

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  • Occurrence of Dermatomyositis Immediately after Mastectomy Subsequent to Severe Chemotherapeutic Drug Eruption 査読

    Yuki Otsuka, Haruki Watanabe, Yuzuki Kano, Noriko Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Ken-ei Sada, Jun Wada

    INTERNAL MEDICINE   56 ( 24 )   3379 - 3383   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.9194-17

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  • Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents 査読

    Takayuki Katsuyama, Ken-Ei Sada, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Eri Katsuyama, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Kohei Miyake, Toru Kiguchi, Jun Wada

    MODERN RHEUMATOLOGY   27 ( 5 )   773 - 777   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/14397595.2016.1259714

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  • Antiangiogenic Therapy for Diabetic Nephropathy 査読

    Katsuyuki Tanabe, Yohei Maeshima, Yasufumi Sato, Jun Wada

    BIOMED RESEARCH INTERNATIONAL   2017   5724069   2017年

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  • Arterial Stiffness is an Independent Risk Factor for Anemia After Percutaneous Native Kidney Biopsy 査読

    Keiko Tanaka, Masashi Kitagawa, Akifumi Onishi, Toshio Yamanari, Ayu Ogawa-Akiyama, Koki Mise, Tatsuyuki Inoue, Hiroshi Morinaga, Haruhito A. Uchida, Hitoshi Sugiyama, Jun Wada

    KIDNEY & BLOOD PRESSURE RESEARCH   42 ( 2 )   284 - 293   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000477453

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  • Azathioprine Intolerance in Japanese Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis 査読

    Michiko Morishita, Haruki Watanabe, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano Narazaki, Noriko Toyota Tatebe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

    INTERNAL MEDICINE   56 ( 13 )   1645 - 1650   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.56.8287

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  • Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis 査読

    Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Ken-Ei Sada, Takayuki Katsuyama, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki, Noriko Tatebe, Katsue Watanabe, Tomoko Kawabata, Jun Wada

    INTERNAL MEDICINE   56 ( 21 )   2943 - 2948   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.8683-16

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  • Development of intracerebral hemorrhage in the short-term clinical course of a patient with microscopic polyangiitis without neurological symptoms at diagnosis: an autopsy case. 査読

    Yoshia Miyawaki, Takayuki Katsuyama, Ken-Ei Sada, Kohei Taniguchi, Yuki Kakio, Jun Wada

    CEN case reports   5 ( 2 )   173 - 178   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 77-year-old man with high-grade fever, progressive renal dysfunction, high serum level of C-reactive protein and positive serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was diagnosed with microscopic polyangiitis with rapidly progressive glomerulonephritis, and remission induction treatment with glucocorticoids and intravenous cyclophosphamide was initiated. Although his general condition improved in a short time, intracerebral hemorrhage occurred 12 days after the initiation of treatment and emergent hematoma evacuation was performed. However, he passed away on day 14. Surprisingly, even though no clinical findings for any organs except for renal involvement was detected before his death, autopsy revealed necrotizing vasculitis affecting various systemic organs including kidney, pancreas, liver, myocardium in ventricle, adipose tissue of the left adrenal gland, small intestine, gallbladder, bronchus, prostate, testis and spleen. It is difficult to detect widespread vasculitis without clinical symptoms and signs in patients with ANCA-associated vasculitis. A whole body assessment tool is necessary to detect unexpected vital organ damage, including cerebral vessels.

    DOI: 10.1007/s13730-016-0219-0

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  • Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm 査読

    Hidemi Takeuchi, Michihiro Okuyama, Haruhito A. Uchida, Yuki Kakio, Ryoko Umebayashi, Yuka Okuyama, Yasuhiro Fujii, Susumu Ozawa, Masashi Yoshida, Yu Oshima, Shunji Sano, Jun Wada

    PLOS ONE   11 ( 10 )   e0164015   2016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)  

    DOI: 10.1371/journal.pone.0164015

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  • ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism 査読

    Zhe Tian, Keishi Miyata, Tsuyoshi Kadomatsu, Haruki Horiguchi, Hiroyuki Fukushima, Shugo Tohyama, Yoshihiro Ujihara, Takahiro Okumura, Satoshi Yamaguchi, Jiabin Zhao, Motoyoshi Endo, Jun Morinaga, Michio Sato, Taichi Sugizaki, Shunshun Zhu, Kazutoyo Terada, Hisashi Sakaguchi, Yoshihiro Komohara, Motohiro Takeya, Naoki Takeda, Kimi Araki, Ichiro Manabe, Keiichi Fukuda, Kinya Otsu, Jun Wada, Toyoaki Murohara, Satoshi Mohri, Jun K. Yamashita, Motoaki Sano, Yuichi Oike

    NATURE COMMUNICATIONS   7   13016   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/ncomms13016

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  • The possible involvement of intestine-derived IgA(1): a case of IgA nephropathy associated with Crohn's disease 査読

    Tomohiro Terasaka, Haruhito A. Uchida, Ryoko Umebayashi, Keiko Tsukamoto, Keiko Tanaka, Masashi Kitagawa, Hitoshi Sugiyama, Hiroaki Tanioka, Jun Wada

    BMC NEPHROLOGY   17 ( 1 )   122   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12882-016-0344-1

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  • Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice 査読

    Takashi Hatanaka, Daisuke Ogawa, Hiromi Tachibana, Jun Eguchi, Tatsuyuki Inoue, Hiroshi Yamada, Kohji Takei, Hirofumi Makino, Jun Wada

    Pharmacology Research and Perspectives   4 ( 4 )   e00239   2016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)   出版者・発行元:Wiley-Blackwell Publishing Ltd  

    DOI: 10.1002/prp2.239

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  • Study about the Efficacy of Metformin to Immune Function in Cancer Patients 査読

    Mototsugu Watanabe, Hiromasa Yamamoto, Shingo Eikawa, Kazuhiko Shien, Tadahiko Shien, Junichi Soh, Katsuyuki Hotta, Jun Wada, Shiro Hinotsu, Toshiyoshi Fujiwara, Katsuyuki Kiura, Hiroyoshi Doihara, Shinichiro Miyoshi, Heiichiro Udono, Shinichi Toyooka

    ACTA MEDICA OKAYAMA   70 ( 4 )   327 - 330   2016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)  

    DOI: 10.18926/AMO/54514

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  • The Efficacy of Rituximab in High-risk Renal Transplant Recipients 査読

    Motoo Araki, Koichiro Wada, Yosuke Mitsui, Risa Kubota, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

    ACTA MEDICA OKAYAMA   70 ( 4 )   295 - 297   2016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)  

    DOI: 10.18926/AMO/54507

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  • Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes 査読

    Jun Wada, Atsuko Nakatsuka

    ACTA MEDICA OKAYAMA   70 ( 3 )   151 - 158   2016年6月

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    記述言語:英語  

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  • Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes 査読

    Kazutoshi Murakami, Jun Eguchi, Kazuyuki Hida, Atsuko Nakatsuka, Akihiro Katayama, Miwa Sakurai, Haruki Choshi, Masumi Furutani, Daisuke Ogawa, Kohji Takei, Fumio Otsuka, Jun Wada

    DIABETES   65 ( 5 )   1255 - 1267   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/db15-1304

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  • Acute idiopathic blue fingers: A young man with Achenbach's syndrome 査読

    Hidemi Takeuchi, Haruhito Adam Uchida, Yuka Okuyama, Jun Wada

    BMJ Case Reports   2016   10.1136/bcr - 2016   2016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)   出版者・発行元:BMJ Publishing Group  

    DOI: 10.1136/bcr-2016-214491

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  • Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis 査読

    Atsuko Nakatsuka, Makoto Matsuyama, Satoshi Yamaguchi, Akihiro Katayama, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Daisuke Ogawa, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Eijiro Watanabe, Jun Wada

    SCIENTIFIC REPORTS   6   21721   2016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)  

    DOI: 10.1038/srep21721

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  • The efficacy of add-on tacrolimus for minor flare in patients with systemic lupus erythematosus: a retrospective study 査読

    H. Watanabe, R. Yamanaka, K-E Sada, S. Zeggar, E. Katsuyama, T. Katsuyama, M. T. Narazaki, N. T. Tatebe, K. Sugiyama, K. S. Watanabe, H. Wakabayashi, T. Kawabata, J. Wada, H. Makino

    LUPUS   25 ( 1 )   54 - 60   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/0961203315600538

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  • Innate immunity in diabetes and diabetic nephropathy 査読

    Jun Wada, Hirofumi Makino

    NATURE REVIEWS NEPHROLOGY   12 ( 1 )   13 - 26   2016年1月

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  • Risk Factors for the Requirement of Antenatal Insulin Treatment in Gestational Diabetes Mellitus 査読

    Mayu Watanabe, Akihiro Katayama, Hidetoshi Kagawa, Daisuke Ogawa, Jun Wada

    Journal of Diabetes Research   2016   9648798   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2016/9648798

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  • Bilateral Abducens Nerve Palsy due to Idiopathic Intracranial Hypertension as an Initial Manifestation of Systemic Lupus Erythematosus 査読

    Eri Katsuyama, Ken-ei Sada, Noriko Tatebe, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Koichi Sugiyama, Katsue S. Watanabe, Hiroshi Wakabayashi, Tomoko Kawabata, Jun Wada, Hirofumi Makino

    INTERNAL MEDICINE   55 ( 8 )   991 - 994   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.55.5990

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  • CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass 査読

    Kitamoto, Aya, Kitamoto, Takuya, Nakamura, Takahiro, Matsuo, Tomoaki, Nakata, Yoshio, Hyogo, Hideyuki, Ochi, Hidenori, Kamohara, Seika, Miyatake, Nobuyuki, Kotani, Kazuaki, Mineo, Ikuo, Wada, Jun, Ogawa, Yuji, Yoneda, Masato, Nakajima, Atsushi, Funahashi, Tohru, Miyazaki, Shigeru, Tokunaga, Katsuto, Masuzaki, Hiroaki, Ueno, Takato, Chayama, Kazuaki, Hamaguchi, Kazuyuki, Yamada, Kentaro, Hanafusa, Toshiaki, Oikawa, Shinichi, Sakata, Toshiie, Tanaka, Kiyoji, Matsuzawa, Yuji, Hotta, Kikuko

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   23 ( 3 )   309 - 319   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN ATHEROSCLEROSIS SOC  

    Aim: Visceral fat accumulation contributes to the development of metabolic syndrome. As visceral fat accumulation increases, adiponectin levels decrease; therefore, adiponectin provides a link between visceral fat accumulation and metabolic disorders. Genome-wide association studies (GWASs) have identified genetic variations in the cadherin 13 (CDH13) gene that are associated with adiponectin levels. Methods: We investigated whether single nucleotide polymorphisms (SNPs) in CDH13 was associated with adiponectin levels and metabolic syndrome traits independent of the visceral fat area (VFA), as measured using computed tomography (CT) in 945 Japanese individuals. Results: We found that three CDH13 SNPs reported by recent GWASs (i.e., rs3865188, rs4783244, and rs12051272) were significantly associated with higher adiponectin levels (P &lt; 1 x 10(-14)), even after adjustment for VFA. However, these adiponectin-inducing alleles of CDH13 SNPs were significantly associated with traits consistent with deteriorating metabolic symptoms, such as higher fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) scores, and triglycerides and lower highdensity lipoprotein (HDL)-cho

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  • Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial 査読

    Sawako Kato, Shoichi Maruyama, Hirofumi Makino, Jun Wada, Daisuke Ogawa, Takashi Uzu, Hisazumi Araki, Daisuke Koya, Keizo Kanasaki, Yutaka Oiso, Motomitsu Goto, Akira Nishiyama, Hiroyuki Kobori, Enyu Imai, Masahiko Ando, Seiichi Matsuo

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   19 ( 6 )   1098 - 1106   2015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)  

    DOI: 10.1007/s10157-015-1106-2

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  • Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis 査読

    Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Motoko Kanzaki, Tomokazu Nunoue, Kazuyuki Hida, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhide Yamamoto, Hiroshi Kiyonari, Hirofumi Makino, Jun Wada

    SCIENTIFIC REPORTS   5   16920   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/srep16920

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  • Successful treatment by mycophenolate mofetil in a patient with focal segmental glomerulosclerosis associated with posterior reversible encephalopathy syndrome. 査読

    Tenta M, Uchida HA, Nunoue T, Umebayashi R, Okuyama Y, Kitagawa M, Maeshima Y, Sugiyama H, Wada J

    CEN case reports   4 ( 2 )   190 - 195   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s13730-014-0165-7

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  • Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes 査読

    Yu Wang, Akihiro Katayama, Takahiro Terami, Xiaoying Han, Tomokazu Nunoue, Dongxiao Zhang, Sanae Teshigawara, Jun Eguchi, Atsuko Nakatsuka, Kazutoshi Murakami, Daisuke Ogawa, Yasuhide Furuta, Hirofumi Makino, Jun Wada

    METABOLISM-CLINICAL AND EXPERIMENTAL   64 ( 6 )   677 - 688   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.metabol.2015.02.004

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  • Risk factors for the development of glucocorticoid-induced diabetes mellitus 査読

    Takayuki Katsuyama, Ken-Ei Sada, Sayaka Namba, Haruki Watanabe, Eri Katsuyama, Toshio Yamanari, Jun Wada, Hirofumi Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   108 ( 2 )   273 - 279   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.diabres.2015.02.010

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  • Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes 査読

    Chigusa Higuchi, Atsuko Nakatsuka, Jun Eguchi, Sanae Teshigawara, Motoko Kanzaki, Akihiro Katayama, Satoshi Yamaguchi, Naoto Takahashi, Kazutoshi Murakami, Daisuke Ogawa, Sakiko Sasaki, Hirofumi Makino, Jun Wada

    METABOLISM-CLINICAL AND EXPERIMENTAL   64 ( 4 )   489 - 497   2015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)  

    DOI: 10.1016/j.metabol.2014.12.003

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  • AUTOIMMUNE PANCREATITIS AND MINIMAL CHANGE NEPHROTIC SYNDROME: AN UNUSUAL ASSOCIATION? 査読

    Yuka Okuyama, Haruhito Adam Uchida, Masafumi Tenta, Tomokazu Nunoue, Ryoko Umebayashi, Hiroshi Morinaga, Shinji Kitamura, Yohei Maeshima, Hitoshi Sugiyama, Jun Wada

    NEPHROLOGY   20 ( 3 )   225 - 226   2015年3月

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  • Cognitive and affective functions in diabetic patients associated with diabetes-related factors, white matter abnormality and aging 査読

    N. Hishikawa, T. Yamashita, K. Deguchi, J. Wada, K. Shikata, H. Makino, K. Abe

    EUROPEAN JOURNAL OF NEUROLOGY   22 ( 2 )   313 - 321   2015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)  

    DOI: 10.1111/ene.12568

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  • Structural design and synthesis of arylalkynyl amide-type peroxisome proliferator-activated receptor γ (PPARγ)-selective antagonists based on the helix12-folding inhibition hypothesis 査読

    Ohashi M, Gamo K, Tanaka Y, Waki M, Beniyama Y, Matsuno K, Wada J, Tenta M, Eguchi J, Makishima M, Matsuura N, Oyama T, Miyachi H

    Eur J Med Chem   90   53 - 67   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ejmech.2014.11.017

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  • ADIPOQ polymorphisms are associated with insulin resistance in Japanese women

    Kitamoto, Aya, Kitamoto, Takuya, So, Rina, Matsuo, Tomoaki, Nakata, Yoshio, Hyogo, Hideyuki, Ochi, Hidenori, Nakamura, Takahiro, Kamohara, Seika, Miyatake, Nobuyuki, Kotani, Kazuaki, Mineo, Ikuo, Wada, Jun, Ogawa, Yuji, Yoneda, Masato, Nakajima, Atsushi, Funahashi, Tohru, Miyazaki, Shigeru, Tokunaga, Katsuto, Masuzaki, Hiroaki, Ueno, Takato, Chayama, Kazuaki, Hamaguchi, Kazayuki, Yamada, Kentaro, Hanafusa, Toshiaki, Oikawa, Shinichi, Sakata, Toshiie, Tanaka, Kiyoji, Matsuzawa, Yuji, Hotta, Kikuko

    ENDOCRINE JOURNAL   62 ( 6 )   513 - 521   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1507/endocrj.EJ14-0574

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  • Factors Associated with Remission and/or Regression of Microalbuminuria in Type 2 Diabetes Mellitus 査読

    Tetsuichiro Ono, Kenichi Shikata, Mikako Obika, Nobuyuki Miyatake, Ryo Kodera, Daisyo Hirota, Jun Wada, Hitomi Kataoka, Daisuke Ogawa, Hirofumi Makino

    ACTA MEDICA OKAYAMA   68 ( 4 )   235 - 241   2014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)  

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  • Long-Term Treatment with the Sodium Glucose Cotransporter 2 Inhibitor, Dapagliflozin, Ameliorates Glucose Homeostasis and Diabetic Nephropathy in db/db Mice 査読

    Naoto Terami, Daisuke Ogawa, Hiromi Tachibana, Takashi Hatanaka, Jun Wada, Atsuko Nakatsuka, Jun Eguchi, Chikage Sato Horiguchi, Naoko Nishii, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

    PLOS ONE   9 ( 6 )   e100777   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0100777

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  • Serum vaspin levels are associated with physical activity or physical fitness in Japanese: a pilot study

    Nobuyuki Miyatake, Jun Wada, Atsuko Nakatsuka, Noriko Sakano, Sanae Teshigawara, Motohiko Miyachi, Izumi Tabata, Takeyuki Numata

    ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE   19 ( 3 )   200 - 206   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12199-013-0375-1

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  • Pemt Deficiency Ameliorates Endoplasmic Reticulum Stress in Diabetic Nephropathy 査読

    Mayu Watanabe, Atsuko Nakatsuka, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Chigusa Higuchi, Akihiro Katayama, Sanae Teshigawara, Jun Eguchi, Daisuke Ogawa, Eijiro Watanabe, Jun Wada, Hirofumi Makino

    PLOS ONE   9 ( 3 )   e92647   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0092647

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  • Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats 査読

    Toru Miyoshi, Kazufumi Nakamura, Masashi Yoshida, Daiji Miura, Hiroki Oe, Satoshi Akagi, Hiroki Sugiyama, Kaoru Akazawa, Tomoko Yonezawa, Jun Wada, Hiroshi Ito

    CARDIOVASCULAR DIABETOLOGY   13   43   2014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)  

    DOI: 10.1186/1475-2840-13-43

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  • Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice 査読

    Hiromi Tachibana, Daisuke Ogawa, Norio Sogawa, Masato Asanuma, Ikuko Miyazaki, Naoto Terami, Takashi Hatanaka, Chikage Sato Horiguchi, Atsuko Nakatsuka, Jun Eguchi, Jun Wada, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

    American Journal of Physiology - Renal Physiology   306 ( 1 )   F105 - F115   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajprenal.00034.2013

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  • Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice 査読

    Hiromi Tachibana, Daisuke Ogawa, Norio Sogawa, Masato Asanuma, Ikuko Miyazaki, Naoto Terami, Takashi Hatanaka, Chikage Sato Horiguchi, Atsuko Nakatsuka, Jun Eguchi, Jun Wada, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   306 ( 1 )   F105 - F115   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajprenal.00034.2013

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  • Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines 査読

    Daisuke Ogawa, Jun Eguchi, Jun Wada, Naoto Terami, Takashi Hatanaka, Hiromi Tachibana, Atsuko Nakatsuka, Chikage Sato Horiguchi, Naoko Nishii, Hirofumi Makino

    PLOS ONE   9 ( 1 )   e85594   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0085594

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  • Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl peptidase-4 inhibitor 査読

    Ken-Ei Sada, Jun Wada, Hiroshi Morinaga, Shigeyuki Tuchimochi, Mayu Uka, Hirofumi Makino

    Clinical Kidney Journal   7 ( 2 )   182 - 185   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press  

    DOI: 10.1093/ckj/sft172

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  • The chemiexcitation of the chemiluminescence of lophine peroxide anions via a partially cyclic transition state

    Lu, G., Wada, J., Kimoto, T., Iga, H., Nishigawa, H., Kimura, M., Hu, Z.

    European Journal of Organic Chemistry   2014 ( 6 )   2014年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/ejoc.201300976

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  • Comparison of New Preservation Solutions, HN-1 and University of Wisconsin Solution, in Pancreas Preservation for Porcine Islet Isolation. 査読

    Katayama A, Noguchi H, Kuise T, Nakatsuka A, Hirota D, Kataoka HU, Kawai T, Inoue K, Imagawa N, Saitoh I, Noguchi Y, Watanabe M, Wada J, Fujiwara T

    Cell medicine   6 ( 1-2 )   3 - 8   2013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)  

    DOI: 10.3727/215517913X674171

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  • Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism 査読

    Kazunori Nakayama, Kazushi Nakao, Yuji Takatori, Junko Inoue, Shoichirou Kojo, Shigeru Akagi, Masaki Fukushima, Jun Wada, Hirofumi Makino

    International Journal of Nephrology and Renovascular Disease   7   25 - 33   2013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)  

    DOI: 10.2147/IJNRD.S54731

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  • Urinary angiotensinogen is a marker for tubular injuries in patients with type 2 diabetes 査読

    Takahiro Terami, Jun Wada, Kentaro Inoue, Atsuko Nakatsuka, Daisuke Ogawa, Sanae Teshigawara, Kazutoshi Murakami, Akihiro Katayama, Jun Eguchi, Hirofumi Makino

    International Journal of Nephrology and Renovascular Disease   6   233 - 240   2013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)  

    DOI: 10.2147/IJNRD.S51829

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  • Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray 査読

    Kentaro Inoue, Jun Wada, Jun Eguchi, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Daisuke Ogawa, Takahiro Terami, Akihiro Katayama, Atsuhito Tone, Izumi Iseda, Kazuyuki Hida, Masao Yamada, Tomohisa Ogawa, Hirofumi Makino

    PLoS ONE   8 ( 10 )   e77118   2013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)  

    DOI: 10.1371/journal.pone.0077118

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  • NUDT3 rs206936 is associated with body mass index in obese Japanese women 査読

    Kitamoto, A., Kitamoto, T., Mizusawa, S., Teranishi, H., So, R., Matsuo, T., Nakata, Y., Hyogo, H., Ochi, H., Nakamura, T., Kamohara, S., Miyatake, N., Kotani, K., Komatsu, R., Itoh, N., Mineo, I., Wada, J., Yoneda, M., Nakajima, A., Funahashi, T., Miyazaki, S., Tokunaga, K., Masuzaki, H., Ueno, T., Chayama, K., Hamaguchi, K., Yamada, K., Hanafusa, T., Oikawa, S., Sakata, T., Tanaka, K., Matsuzawa, Y., Nakao, K., Sekine, A., Hotta, K.

    Endocrine Journal   60 ( 8 )   991 - 1000   2013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)  

    DOI: 10.1507/endocrj.EJ13-0100

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  • Cell Cycle Abnormality in Metabolic Syndrome and Nuclear Receptors as an Emerging Therapeutic Target 査読

    Atsuko Nakatsuka, Jun Wada, Hirofumi Makino

    ACTA MEDICA OKAYAMA   67 ( 3 )   129 - 134   2013年6月

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  • Visceral Adipose Tissue-derived Serine Proteinase Inhibitor Inhibits Apoptosis of Endothelial Cells as a Ligand for the Cell-Surface GRP78/Voltage-dependent Anion Channel Complex 査読

    Atsuko Nakatsuka, Jun Wada, Izumi Iseda, Sanae Teshigawara, Kanji Higashio, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Kazuyuki Hida, Jun Eguchi, Daisuke Ogawa, Yasushi Matsuki, Ryuji Hiramatsu, Hideo Yagita, Shigeru Kakuta, Yoichiro Iwakura, Hirofumi Makino

    CIRCULATION RESEARCH   112 ( 5 )   771 - +   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1161/CIRCRESAHA.111.300049

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  • Current status of the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in Japan 査読

    Koichi Sugiyama, Ken-Ei Sada, Michiko Kurosawa, Jun Wada, Hirofumi Makino

    Clinical and Experimental Nephrology   17 ( 1 )   51 - 58   2013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)  

    DOI: 10.1007/s10157-012-0651-1

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  • Inflammation and the pathogenesis of diabetic nephropathy 査読

    Jun Wada, Hirofumi Makino

    CLINICAL SCIENCE   124 ( 3-4 )   139 - 152   2013年2月

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  • The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO) 査読

    Kazutoshi Murakami, Jun Wada, Daisuke Ogawa, Chikage Sato Horiguchi, Tomoko Miyoshi, Motofumi Sasaki, Haruhito A. Uchida, Yoshio Nakamura, Hirofumi Makino

    DIABETES & VASCULAR DISEASE RESEARCH   10 ( 1 )   93 - 96   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/1479164112444640

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  • Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease 査読

    Yuko Kurose, Jun Wada, Motoko Kanzaki, Sanae Teshigawara, Atsuko Nakatsuka, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Mayu Watanabe, Chigusa Higuchi, Jun Eguchi, Nobuyuki Miyatake, Hirofumi Makino

    BMC NEPHROLOGY   14   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/1471-2369-14-23

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  • Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population 査読

    Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Rina So, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   20 ( 4 )   336 - 350   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.5551/jat.14589

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  • The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO) (vol 10, pg 93, 2013)

    Jun Wada

    Diabetes and Vascular Disease Research   10 ( 6 )   554 - 554   2013年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/1479164113507658

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  • Erratum: Telmisartan attenutes diabetic nephropathy by suppressing oxisative stress in db/db mice (Nephron - Experimental Nephrology (2012) 121 (e97-e108) DOI: 10.1159/00343102)

    Sato-Horiguchi, C., Ogawa, D., Wada, J., Tachibana, H., Kodera, R., Eguchi, J., Nakatsuka, A., Terami, N., Shikata, K., Makino, H.

    Nephron - Experimental Nephrology   123 ( 3-4 )   46 - 46   2013年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000355989

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  • Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines

    Jun Wada

    Diabetes   2013年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/JOURNAL.PONE.0085594

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  • The serum vaspin levels are reduced in Japanese chronic hemodialysis patients 査読

    Junko Inoue, Jun Wada, Sanae Teshigawara, Kazuyuki Hida, Atsuko Nakatsuka, Yuji Takatori, Shoichirou Kojo, Shigeru Akagi, Kazushi Nakao, Nobuyuki Miyatake, John F. McDonald, Hirofumi Makino

    BMC NEPHROLOGY   13   2012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)  

    DOI: 10.1186/1471-2369-13-163

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  • Case of emphysematous cholecystitis in a patient with type 2 diabetes mellitus associated with schizophrenia 査読

    Ayu Ogawa, Kenichi Shikata, Haruhito Adam Uchida, Susumu Shinoura, Naosuke Yokomichi, Daisuke Ogawa, Chicage Sato-Horiguchi, Takahito Yagi, Jun Wada, Hirofumi Makino

    JOURNAL OF DIABETES INVESTIGATION   3 ( 6 )   534 - 535   2012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)  

    DOI: 10.1111/j.2040-1124.2012.00232.x

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  • Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex 査読

    Atsuko Nakatsuka, Jun Wada, Izumi Iseda, Sanae Teshigawara, Kanji Higashio, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Kazuyuki Hida, Jun Eguchi, Chikage Sato Horiguchi, Daisuke Ogawa, Yasushi Matsuki, Ryuji Hiramatsu, Hideo Yagita, Shigeru Kakuta, Yoichiro Iwakura, Hirofumi Makino

    DIABETES   61 ( 11 )   2823 - 2832   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/db12-0232

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  • Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy 査読

    Hiromi Tachibana, Daisuke Ogawa, Yuichi Matsushita, Dennis Bruemmer, Jun Wada, Sanae Teshigawara, Jun Eguchi, Chikage Sato-Horiguchi, Haruhito Adam Uchida, Kenichi Shikata, Hirofumi Makino

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   23 ( 11 )   1835 - 1846   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1681/ASN.2012010022

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  • Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice 査読

    Daisuke Kawai, Akinobu Takaki, Atsuko Nakatsuka, Jun Wada, Naofumi Tamaki, Tetsuya Yasunaka, Kazuko Koike, Ryuichiro Tsuzaki, Kazuyuki Matsumoto, Yasuhiro Miyake, Hidenori Shiraha, Manabu Morita, Hirofumi Makino, Kazuhide Yamamoto

    HEPATOLOGY   56 ( 3 )   912 - 921   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/hep.25782

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  • Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 at SERPINA12 Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population 査読

    Sanae Teshigawara, Jun Wada, Kazuyuki Hida, Atsuko Nakatsuka, Jun Eguchi, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Izumi Iseda, Yuichi Matsushita, Nobuyuki Miyatake, John F. McDonald, Kikuko Hotta, Hirofumi Makino

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   97 ( 7 )   E1202 - E1207   2012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)  

    DOI: 10.1210/jc.2011-3297

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  • Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography 査読

    Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Rina So, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

    JOURNAL OF HUMAN GENETICS   57 ( 5 )   305 - 310   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/jhg.2012.21

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  • RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21(Cip1) pathway in adipocytes 査読

    Atsuko Nakatsuka, Jun Wada, Kazuyuki Hida, Aya Hida, Jun Eguchi, Sanae Teshigawara, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Daisuke Ogawa, Hiroyuki Kagechika, Hirofumi Makino

    JOURNAL OF PATHOLOGY   226 ( 5 )   784 - 795   2012年4月

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    DOI: 10.1002/path.3001

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  • Impact of circulating vaspin levels on metabolic variables in elderly twins 査読

    K. Hida, P. Poulsen, S. Teshigawara, E. Nilsson, M. Friedrichsen, R. Ribel-Madsen, L. Grunnet, S. S. Lund, J. Wada, A. Vaag

    DIABETOLOGIA   55 ( 2 )   530 - 532   2012年2月

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  • Galectin-9 and T Cell Immunoglobulin Mucin-3 Pathway Is a Therapeutic Target for Type 1 Diabetes 査読

    Motoko Kanzaki, Jun Wada, Koichi Sugiyama, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Jun Eguchi, Hisaya Akiba, Hideo Yagita, Hirofumi Makino

    ENDOCRINOLOGY   153 ( 2 )   612 - 620   2012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)  

    DOI: 10.1210/en.2011-1579

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  • Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women 査読

    Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

    JOURNAL OF HUMAN GENETICS   57 ( 1 )   46 - 51   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/jhg.2011.127

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  • The therapeutic potential of synthetic human atrial natriuretic peptide in nephrotic syndrome: a randomized controlled trial 査読

    Jun Wada

    International Journal of Nephrology and Renovascular Disease   5   91 - 6   2012年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2147/IJNRD.S32191

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  • A Case of Type 2 Diabetes and Metastatic Liver Cancer Exhibiting Hypercholesterolemia with Abnormal Lipoproteins 査読

    Motoko Kanzaki, Jun Wada, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Junichiro Nasu, Kazuhide Yamamoto, Hirofumi Makino

    INTERNAL MEDICINE   51 ( 6 )   619 - 623   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.51.6486

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  • Telmisartan Attenuates Diabetic Nephropathy by Suppressing Oxidative Stress in db/db Mice 査読

    Chikage Sato-Horiguchi, Daisuke Ogawa, Jun Wada, Hiromi Tachibana, Ryo Kodera, Jun Eguchi, Atsuko Nakatsuka, Naoto Terami, Kenichi Shikata, Hirofumi Makino

    NEPHRON EXPERIMENTAL NEPHROLOGY   121 ( 3-4 )   E97 - E108   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000343102

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  • Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area 査読

    Kikuko Hotta, Takuya Kitamoto, Aya Kitamoto, Seiho Mizusawa, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

    JOURNAL OF HUMAN GENETICS   56 ( 10 )   716 - 719   2011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)  

    DOI: 10.1038/jhg.2011.86

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  • Two novel mutations of lecithin:cholesterol acyltransferase (LCAT) gene and the influence of APOE genotypes on clinical manifestations 査読

    Katayama, A., Wada, J., Kataoka, H.U., Yamasaki, H., Teshigawara, S., Terami, T., Inoue, K., Kanzaki, M., Murakami, K., Nakatsuka, A., Sugiyama, H., Koide, N., Bujo, H., Makino, H.

    NDT Plus   4 ( 5 )   299 - 302   2011年10月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/ndtplus/sfr091

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  • Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population 査読

    Kikuko Hotta, Takuya Kitamoto, Aya Kitamoto, Seiho Mizusawa, Tomoaki Matsuo, Yoshio Nakata, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

    JOURNAL OF HUMAN GENETICS   56 ( 9 )   647 - 651   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/jhg.2011.74

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  • Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy 査読

    Naomi Watanabe, Kenichi Shikata, Yasushi Shikata, Kei Sarai, Kazuyoshi Omori, Ryo Kodera, Chikage Sato, Jun Wada, Hirofumi Makino

    ACTA MEDICA OKAYAMA   65 ( 4 )   247 - 257   2011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)  

    DOI: 10.18926/AMO/46850

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  • Icodextrin Increases Technique Survival Rate in Peritoneal Dialysis Patients with Diabetic Nephropathy by Improving Body Fluid Management: A Randomized Controlled Trial 査読

    Yuji Takatori, Shigeru Akagi, Hitoshi Sugiyama, Junko Inoue, Shoichiro Kojo, Hiroshi Morinaga, Kazushi Nakao, Jun Wada, Hirofumi Makino

    CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   6 ( 6 )   1337 - 1344   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2215/CJN.10041110

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  • Emphysematous Cystitis in a Patient with Type 2 Diabetes Mellitus 査読

    Noriko Toyota, Daisuke Ogawa, Keita Ishii, Kyoji Hirata, Jun Wada, Kenichi Shikata, Hirofumi Makino

    ACTA MEDICA OKAYAMA   65 ( 2 )   129 - 133   2011年4月

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  • Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis after subtotal nephrectomy 査読

    Yuichi Kido, Daisuke Ogawa, Kenichi Shikata, Motofumi Sasaki, Ryo Nagase, Shinichi Okada, Hitomi Usui Kataoka, Jun Wada, Hirofumi Makino

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   15 ( 2 )   212 - 219   2011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)  

    DOI: 10.1007/s10157-010-0388-7

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  • The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration 査読

    Motofumi Sasaki, Kenichi Shikata, Shinichi Okada, Satoshi Miyamoto, Shingo Nishishita, Hitomi Usui Kataoka, Chikage Sato, Jun Wada, Daisuke Ogawa, Hirofumi Makino

    ACTA MEDICA OKAYAMA   65 ( 2 )   81 - 89   2011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)  

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  • Activation of Peroxisome Proliferator-Activated Receptor delta Inhibits Streptozotocin-Induced Diabetic Nephropathy Through Anti-Inflammatory Mechanisms in Mice 査読

    Yuichi Matsushita, Daisuke Ogawa, Jun Wada, Noriko Yamamoto, Kenichi Shikata, Chikage Sato, Hiromi Tachibana, Noriko Toyota, Hirofumi Makino

    DIABETES   60 ( 3 )   960 - 968   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/db10-1361

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  • P-Selectin Glycoprotein Ligand-1 Deficiency Is Protective Against Obesity-Related Insulin Resistance 査読

    Chikage Sato, Kenichi Shikata, Daisho Hirota, Motofumi Sasaki, Shingo Nishishita, Satoshi Miyamoto, Ryo Kodera, Daisuke Ogawa, Atsuhito Tone, Hitomi Usui Kataoka, Jun Wada, Nobuo Kajitani, Hirofumi Makino

    DIABETES   60 ( 1 )   189 - 199   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/db09-1894

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  • High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells 査読

    Daisuke Ogawa, Masato Asanuma, Ikuko Miyazaki, Hiromi Tachibana, Jun Wada, Norio Sogawa, Takeshi Sugaya, Shinji Kitamura, Yohei Maeshima, Kenichi Shikata, Hirofumi Makino

    EXPERIMENTAL DIABETES RESEARCH   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2011/534872

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  • Discovery of Genes Related to Diabetic Nephropathy in Various Animal Models by Current Techniques 査読

    Jun Wada, Lin Sun, Yashpal S. Kanwar

    EXPERIMENTAL MODELS FOR RENAL DISEASES: PATHOGENESIS AND DIAGNOSIS   169   161 - 174   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000313951

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  • [Obesity: Progress in diagnosis and treatment; Topics, IV. Recent topics: 3. Obesity and new secretory factors; 1) Vaspin].

    Wada, J., Teshigawara, S., Nakatsuka, A., Makino, H.

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   100 ( 4 )   2011年

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    DOI: 10.2169/naika.100.996

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  • Regulation of human serum vaspin levels and metabolic syndrome

    Wada, J.

    Therapeutic Research   32 ( 6 )   2011年

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  • [Chronic kidney disease].

    Katayama, A., Wada, J., Makino, H.

    Nihon rinsho. Japanese journal of clinical medicine   69 Suppl 1   2011年

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  • [Chemerin, RBP4 and vaspin].

    Wada, J., Teshigawara, S., Nakatsuka, A.

    Nihon rinsho. Japanese journal of clinical medicine   69 Suppl 1   2011年

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  • Insufficient control of morning home blood pressure in Japanese patients with hypertension associated with diabetes mellitus 査読

    Haruhito A. Uchida, Yoshio Nakamura, Hisanao Norii, Masanobu Kaihara, Yoshihisa Hanayama, Ken-Ei Sada, Jun Wada, Kenichi Shikata, Hirofumi Makino

    JOURNAL OF DIABETES INVESTIGATION   1 ( 6 )   266 - 272   2010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)  

    DOI: 10.1111/j.2040-1124.2010.00056.x

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  • Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population 査読

    Kikuko Hotta, Michihiro Nakamura, Takahiro Nakamura, Tomoaki Matsuo, Yoshio Nakata, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Hiroaki Masuzaki, Takato Ueno, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Yusuke Nakamura, Naoyuki Kamatani

    JOURNAL OF HUMAN GENETICS   55 ( 11 )   738 - 742   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/jhg.2010.99

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  • Peramivir for Severe Influenza Infection in a Patient with Diabetic Nephropathy 査読

    Tatsuyo Nasu, Daisuke Ogawa, Jun Wada, Hirofumi Makino

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   182 ( 9 )   1209 - 1210   2010年11月

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    記述言語:英語  

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  • In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7 査読

    Qingxian Zhang, Yonghong Shi, Jun Wada, Sandra M. Malakauskas, Maodong Liu, Yunzhuo Ren, Chunyang Du, Huijun Duan, Yingmin Li, Ying Li, Yanling Zhang

    PLOS ONE   5 ( 7 )   2010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)  

    DOI: 10.1371/journal.pone.0011709

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  • Comparison of Insulin Detemir and Insulin Glargine on Glycemic Variability in Patients with Type 1 and Type 2 Diabetes 査読

    A. Tone, I. Iseda, C. Higuchi, K. Tsukamoto, A. Katayama, Y. Matsushita, K. Hida, J. Wada, K. Shikata

    EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES   118 ( 5 )   320 - 324   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1055/s-0029-1243230

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  • Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy 査読

    Ai Nakao, Kazushi Nakao, Yuji Takatori, Syoichirou Kojo, Junko Inoue, Shigeru Akagi, Hitoshi Sugiyama, Jun Wada, Hirofumi Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   25 ( 5 )   1479 - 1488   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/ndt/gfp479

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  • The Usefulness of Super-Selective Computed Tomography Angiography (CTA) for Diagnosing and Localizing a Small Insulinoma 査読

    Akihiro Katayama, Izumi Iseda, Atsuhito Tone, Yuichi Matsushita, Kentaro Inoue, Keiko Tsukamoto, Haruhiro Yamashita, Ichiro Yamadori, Jun Wada, Kazuyuki Hida

    INTERNAL MEDICINE   49 ( 18 )   1983 - 1986   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.49.3739

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  • Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population 査読

    Kikuko Hotta, Michihiro Nakamura, Takahiro Nakamura, Tomoaki Matsuo, Yoshio Nakata, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Takato Ueno, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura

    JOURNAL OF HUMAN GENETICS   54 ( 12 )   727 - 731   2009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)  

    DOI: 10.1038/jhg.2009.106

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  • Endothelial barrier protection by FTY720 under hyperglycemic condition: involvement of focal adhesion kinase, small GTPases, and adherens junction proteins 査読

    Kei Sarai, Kenichi Shikata, Yasushi Shikata, Kazuyoshi Omori, Naomi Watanabe, Motofumi Sasaki, Shingo Nishishita, Jun Wada, Noriko Goda, Noriyuki Kataoka, Hirofumi Makino

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   297 ( 4 )   C945 - C954   2009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)  

    DOI: 10.1152/ajpcell.00606.2008

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  • Historical chronology of basic and clinical research in diabetic nephropathy and contributions of Japanese scientists 査読

    Jun Wada, Hirofumi Makino

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   13 ( 5 )   405 - 414   2009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)  

    DOI: 10.1007/s10157-009-0175-5

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  • Enhanced interaction between focal adhesion and adherens junction proteins: Involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement 査読

    Xiaoguang Sun, Yasushi Shikata, Lichun Wang, Kazuyoshi Ohmori, Naoko Watanabe, Jun Wada, Kenichi Shikata, Konstantin G. Birukov, Hirofumi Makino, Jeffrey R. Jacobson, Steven M. Dudek, Joe G. N. Garcia

    MICROVASCULAR RESEARCH   77 ( 3 )   304 - 313   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.mvr.2008.12.004

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  • Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome 査読

    Kikuko Hotta, Takahiro Nakamura, Junichi Takasaki, Hiroshi Takahashi, Atsushi Takahashi, Yoshio Nakata, Seika Kamohara, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura

    JOURNAL OF HUMAN GENETICS   54 ( 4 )   230 - 235   2009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)  

    DOI: 10.1038/jhg.2009.16

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  • Rap1b GTPase Ameliorates Glucose-Induced Mitochondrial Dysfunction 査読

    Lin Sun, Ping Xie, Jun Wada, Naoki Kashihara, Fu-you Liu, Yanan Zhao, Deepak Kumar, Sumant S. Chugh, Farhad R. Danesh, Yashpal S. Kanwar

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   19 ( 12 )   2293 - 2301   2008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)  

    DOI: 10.1681/ASN.2008030336

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  • Bilateral dystonia in type 1 diabetes: A case report 査読

    Akihiro Yasuhara, Jun Wada, Hirofumi Makino

    Journal of Medical Case Reports   2   352   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/1752-1947-2-352

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  • Collectrin Is Involved in the Development of Salt-Sensitive Hypertension by Facilitating the Membrane Trafficking of Apical Membrane Proteins via Interaction With Soluble N-Ethylmaleiamide-Sensitive Factor Attachment Protein Receptor Complex 査読

    Akihiro Yasuhara, Jun Wada, Sandra M. Malakauskas, Yanling Zhang, Jun Eguchi, Atsuko Nakatsuka, Kazutoshi Murakami, Motoko Kanzaki, Sanae Teshigawara, Kazuya Yamagata, Thu H. Le, Hirofumi Makino

    CIRCULATION   118 ( 21 )   2146 - 2155   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1161/CIRCULATIONAHA.108.787259

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  • INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese 査読

    Kikuko Hotta, Michihiro Nakamura, Yoshio Nakata, Tomoaki Matsuo, Seika Kamohara, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Tohru Funahashi, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Kiyoji Tanaka, Naoyuki Kamatani, Yusuke Nakamura

    JOURNAL OF HUMAN GENETICS   53 ( 9 )   857 - 862   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10038-008-0317-8

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  • Variations in the FTO gene are associated with severe obesity in the Japanese 査読

    Kikuko Hotta, Yoshio Nakata, Tomoaki Matsuo, Seika Kamohara, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Tohru Funahashi, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Kiyoji Tanaka, Naoyuki Kamatani, Yusuke Nakamura

    JOURNAL OF HUMAN GENETICS   53 ( 6 )   546 - 553   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10038-008-0283-1

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  • Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysis 査読

    Kousuke Fukuoka, Kazushi Nakao, Hisanori Morimoto, Ai Nakao, Yuji Takatori, Katsuhiko Arimoto, Masafumi Taki, Jun Wada, Hirofumi Makino

    NEPHROLOGY   13 ( 4 )   278 - 283   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1440-1797.2007.00864.x

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  • Procollagen C-proteinase enhancer-1 (POPE-1) interacts with beta 2-microglobulin (beta 2-m) and may help initiate beta 2-m amyloid fibril formation in connective tissues 査読

    Hisanori Morimoto, Jun Wada, Bernard Font, Joni D. Mott, David J. S. Hulmes, Tadakazu Ookoshi, Hironobu Naiki, Akihiro Yasuhara, Atsuko Nakatsuka, Kousuke Fukuoka, Yuji Takatori, Haruo Ichikawa, Shigeru Akagi, Kazushi Nakao, Hirofumi Makino

    MATRIX BIOLOGY   27 ( 3 )   211 - 219   2008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)  

    DOI: 10.1016/j.matbio.2007.11.005

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  • Vaspin: a novel serpin with insulin-sensitizing effects 査読

    Jun Wada

    EXPERT OPINION ON INVESTIGATIONAL DRUGS   17 ( 3 )   327 - 333   2008年3月

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  • Diabetic nephropathy: Mechanisms of renal disease progression 査読

    Yashpal S. Kanwar, Jun Wada, Lin Sun, Ping Xie, Elisabeth I. Wallner, Sheldon Chen, Sumant Chugh, Farhad R. Danesh

    EXPERIMENTAL BIOLOGY AND MEDICINE   233 ( 1 )   4 - 11   2008年1月

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  • Comparison of serum uric acid levels between Japanese with and without metabolic syndrome

    Numata, T., Miyatake, N., Wada, J., Makino, H.

    Diabetes Research and Clinical Practice   80 ( 1 )   2008年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.diabres.2007.10.031

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  • Vaspin and insulin resistance

    Wada, J.

    Rinsho byori. The Japanese journal of clinical pathology   56 ( 8 )   2008年

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    掲載種別:研究論文(学術雑誌)  

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  • Association of single-nucleotide polymorphisms in MTMR9 gene with obesity 査読

    Takahiro Yanagiya, Atsushi Tanabe, Aritoshi Iida, Susumu Saito, Akihiro Sekine, Atsushi Takahashi, Tatsuhiko Tsunoda, Seika Kamohara, Yoshio Nakata, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Tohru Funahashi, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura, Kikuko Hotta

    HUMAN MOLECULAR GENETICS   16 ( 24 )   3017 - 3026   2007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)  

    DOI: 10.1093/hmg/ddm260

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  • Collectrin, a homologue of ACE2, its transcriptional control and functional perspectives 査読

    Yanling Zhang, Jun Wada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   363 ( 1 )   1 - 5   2007年11月

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  • Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells 査読

    Kazuyoshi Omori, Yasushi Shikata, Kei Sarai, Naomi Watanabe, Jun Wada, Noriko Goda, Noriyuki Kataoka, Kenichi Shikata, Hirofumi Makino

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   293 ( 5 )   C1523 - C1531   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajpcell.00524.2006

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  • Linkage between oxygen uptake at ventilatory threshold and muscle strength in subjects with and without metabolic syndrome 査読

    Nobuyuki Miyatake, Takeshi Saito, Jun Wada, Hidetaka Nishikawa, Sumiko Matsumoto, Motohiko Miyachi, Masafumi Fujii, Hirofumi Makino, Takeyuki Numata

    ACTA MEDICA OKAYAMA   61 ( 5 )   255 - 259   2007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)  

    DOI: 10.18926/AMO/32895

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  • Comparison of ventilatory threshold and exercise habits between Japanese men with and without metabolic syndrome 査読

    Nobuyuki Miyatake, Takeshi Saito, Jun Wada, Motohiko Miyachi, Izumi Tabata, Sumiko Matsumoto, Hidetaka Nishikawa, Hirofumi Makino, Takeyuki Numata

    DIABETES RESEARCH AND CLINICAL PRACTICE   77 ( 2 )   314 - 319   2007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)  

    DOI: 10.1016/j.diabres.2006.11.008

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  • Re-evaluation of waist circumference in metabolic syndrome: A comparison between Japanese men and women 査読

    Nobuyuki Miyatake, Jun Wada, Sumiko Matsumoto, Hidetaka Nishikawa, Hirofumi Makino, Takeyuki Numata

    ACTA MEDICA OKAYAMA   61 ( 3 )   167 - 169   2007年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/32900

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  • Urinary PGDS levels are associated with vascular injury in type 2 diabetes patients 査読

    Ritsuko Yoshikawa, Jun Wada, Kousuke Seiki, Takashi Matsuoka, Satoshi Miyamoto, Kenji Takahashi, Sachiko Ota, Kazuhi Taniai, Kazuyuki Hida, Minoru Yamakado, Kenichi Shikata, Yoshio Uehara, Yoshihiro Urade, Hirofumi Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   76 ( 3 )   358 - 367   2007年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.diabres.2006.09.004

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  • The Role for HNF-1 beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells 査読

    Yanling Zhang, Jun Wada, Akihiro Yasuhara, Izumi Iseda, Jun Eguchi, Kenji Fukui, Qin Yang, Kazuya Yamagata, Thomas Hiesberger, Peter Igarashi, Hong Zhang, Haiyan Wang, Shigeru Akagi, Yashpal S. Kanwar, Hirofumi Makino

    PLOS ONE   2 ( 5 )   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0000414

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  • Comparison of muscle strength between Japanese men with and without metabolic syndrome 査読

    Nobuyuki Miyatake, Jun Wada, Takeshi Saito, Hidetaka Nishikawa, Sumiko Matsumoto, Motohiko Miyachi, Hirofumi Makino, Takeyuki Numata

    ACTA MEDICA OKAYAMA   61 ( 2 )   99 - 102   2007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)  

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  • Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-kappa B activation 査読

    Sakiko Ohga, Kenichi Shikata, Kosuke Yozai, Shinichi Okada, Daisuke Ogawa, Hitomi Usui, Jun Wada, Yasushi Shikata, Hirofumi Makino

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   292 ( 4 )   F1141 - F1150   2007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)  

    DOI: 10.1152/ajprenal.00288.2005

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  • Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-κB activation 査読

    Sakiko Ohga, Kenichi Shikata, Kosuke Yozai, Shinichi Okada, Daisuke Ogawa, Hitomi Usui, Jun Wada, Yasushi Shikata, Hirofumi Makino

    American Journal of Physiology - Renal Physiology   292 ( 4 )   F1141 - F1150   2007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)  

    DOI: 10.1152/ajprenal.00288.2005

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  • Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity 査読

    Atsushi Tanabe, Takahiro Yanagiya, Aritoshi Iida, Susumu Saito, Akihiro Sekine, Atsushi Takahashi, Takahiro Nakamura, Tatsuhiko Tsunoda, Seika Kamohara, Yoshio Nakata, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Kazuyuki Hamaguchi, Tatsuo Shimada, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura, Kikuko Hotta

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   92 ( 3 )   1145 - 1154   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1210/jc.2006-1808

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  • Changes of gene expression profiles in macrophages stimulated by angiotensin II - Angiotensin II induces MCP-2 through AT(1)-receptor 査読

    Atsuhito Tone, Kenichi Shikata, Daisuke Ogawa, Sakiko Sasaki, Ryo Nagase, Motofumi Sasaki, Kosuke Yozai, Hitomi Kataoka Usui, Shinichi Okada, Jun Wada, Yasushi Shikata, Hirofumi Makino

    JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM   8 ( 1 )   45 - 50   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3317/jraas.2007.007

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  • Macrophage scavenger receptor-A-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation 査読

    Hitorni Kataoka Usui, Kenichi Shikata, Motofurni Sasaki, Shinichi Okada, Mitsuhiro Matsuda, Yasushi Shikata, Daisuke Ogawa, Yuichi Kido, Ryo Nagase, Kosuke Yozai, Sakiko Ohga, Atsuhito Tone, Jun Wada, Masahiro Takeya, Seikoh Horiuchi, Tatsuhiko Kodama, Hirofunti Makino

    DIABETES   56 ( 2 )   363 - 372   2007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)  

    DOI: 10.2337/db06-0359

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  • Serpins and the metabolic syndrome 査読

    Jun Wada

    Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity   411 - 423   2007年1月

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:World Scientific Publishing Co.  

    DOI: 10.1142/9789812707543_0018

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  • Hemophagocytic syndrome associated with fatal veno-occlusive disease in the liver 査読

    Atsuko Nakatsuka, Jun Wada, Ryo Nagase, Masaya Takeda, Tadashi Yoshino, Hirofumi Makino

    INTERNAL MEDICINE   46 ( 8 )   495 - 499   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.46.6294

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  • Severe hypoglycemia induced by IGF-II producing non-islet cell tumor

    Kanzaki, M., Kashihara, H., Kiura, K., Murakami, K., Iwagaki, H., Wada, J., Makino, H.

    Internal Medicine   46 ( 13 )   1061 - 1061   2007年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.46.6455

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  • Hypolipidemia of renal diseases

    Teshigawara, S., Wada, J., Makino, H.

    Nippon rinsho. Japanese journal of clinical medicine   65 Suppl 7   2007年

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  • Erratum: Macrophage scavenger receptor-A - Deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation (Diabetes (2007) 56, (263-372))

    Usui, H.K., Shikata, K., Sasaki, M., Okada, S., Matsuda, M., Shikata, Y., Ogawa, D., Kido, Y., Nagase, R., Yozai, K., Ohga, S., Tone, A., Wada, J., Takeya, M., Horiuchi, S., Kodama, T., Makino, H.

    Diabetes   56 ( 3 )   897 - 897   2007年

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    DOI: 10.2337/db07-er03

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  • Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms 査読

    T Okada, J Wada, K Hida, J Eguchi, Hashimoto, I, M Baba, A Yasuhara, K Shikata, H Makino

    DIABETES   55 ( 6 )   1666 - 1677   2006年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/db05-1285

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  • Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects 査読

    Izumi Hashimoto, Jun Wada, Aya Hida, Masako Baba, Nobuyuki Miyatake, Jun Eguchi, Kenichi Shikata, Hirofumi Makino

    OBESITY   14 ( 5 )   799 - 811   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/oby.2006.93

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  • Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects 査読

    Izumi Hashimoto, Jun Wada, Aya Hida, Masako Baba, Nobuyuki Miyatake, Jun Eguchi, Kenichi Shikata, Hirofumi Makino

    Obesity   14 ( 5 )   799 - 811   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/oby.2006.93

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  • Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production 査読

    Yanling Zhang, Jun Wada, Izumi Hashimoto, Jun Eguchi, Akihiro Yasuhara, Yashpal S. Kanwar, Kenichi Shikata, Hirofumi Makino

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   17 ( 4 )   1090 - 1101   2006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)  

    DOI: 10.1681/ASN.2005111148

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  • The application of synthetic hANP in diabetic nephropathy with nephrotic syndrome 査読

    Y Kikumoto, J Wada, H Makino

    DIABETES CARE   29 ( 1 )   172 - 173   2006年1月

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  • Relationship between metabolic syndrome and cigarette smoking in the Japanese population 査読

    Nobuyuki Miyatake, Jun Wada, Yuriko Kawasaki, Kenji Nishii, Hirofumi Makino, Takeyuki Numata

    INTERNAL MEDICINE   45 ( 18 )   1039 - 1043   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.45.1850

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  • Relationship between metabolic syndrome and proteinuria in the Japanese population 査読

    Nobuyuki Miyatake, Jun Wada, Yuriko Kawasaki, Sumiko Matsumoto, Hirofumi Makino, Takeyuki Numata

    INTERNAL MEDICINE   45 ( 9 )   599 - 603   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.45.1681

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  • Molecular biology of regulation in renal functions; biosynthesis, metabolism, and action of insulin and glucagon

    Nakatsuka, A., Wada, J., Makino, H.

    Nippon rinsho. Japanese journal of clinical medicine   64 Suppl 2   2006年

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  • ACAM, vaspin

    Wada, J., Hida, K., Eguchi, J., Makino, H.

    Nippon rinsho. Japanese journal of clinical medicine   64 Suppl 9   2006年

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  • The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation 査読

    K Fukui, Q Yang, Y Cao, N Takahashi, H Hatakeyama, HY Wang, J Wada, YL Zhang, L Marselli, T Nammo, K Yoneda, M Onishi, S Higashiyama, Y Matsuzawa, FJ Gonzalez, GC Weir, H Kasai, L Shimomura, J Miyagawa, CB Wollheim, K Yamagata

    CELL METABOLISM   2 ( 6 )   373 - 384   2005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)  

    DOI: 10.1016/j.cmet.2005.11.003

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  • Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients 査読

    H Morimoto, K Nakao, K Fukuoka, A Sarai, A Yano, T Kihara, S Fukuda, J Wada, H Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   20 ( 12 )   2775 - 2782   2005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)  

    DOI: 10.1093/ndt/gfi121

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  • Modulation of renal-specific oxidoreductase/myo-inositol oxygenase by high-glucose ambience 査読

    B Nayak, P Xie, S Akagi, QW Yang, L Sun, J Wada, A Thakur, FR Danesh, SS Chugh, YS Kanwar

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   102 ( 50 )   17952 - 17957   2005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)  

    DOI: 10.1073/pnas.0509089102

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  • Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes 査読

    A Nakamura, K Shikata, M Hiramatsu, T Nakatou, T Kitamura, J Wada, T Itoshima, H Makino

    DIABETES CARE   28 ( 12 )   2890 - 2895   2005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)  

    DOI: 10.2337/diacare.28.12.2890

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  • Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions 査読

    K Yozai, K Shikata, M Sasaki, A Tone, S Ohga, H Usui, S Okada, J Wada, R Nagase, D Ogawa, Y Shikata, H Makino

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   16 ( 11 )   3326 - 3338   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1681/ASN.2004111011

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  • Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats 査読

    A Tone, K Shikata, M Sasaki, S Ohga, K Yozai, S Nishishita, H Usui, R Nagase, D Ogawa, S Okada, Y Shikata, J Wada, H Makino

    DIABETOLOGIA   48 ( 11 )   2402 - 2411   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00125-005-1945-6

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  • Galectin-9 inhibits glomerular hypertrophy in db/db diabetic mice via cell-cycle-dependent mechanisms 査読

    M Baba, J Wada, J Eguchi, Hashimoto, I, T Okada, A Yasuhara, K Shikata, YS Kanwar, H Makino

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   16 ( 11 )   3222 - 3234   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1681/ASN.2004110915

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  • Gene delivery of Tim44 reduces mitochondrial superoxide production and ameliorates neointimal proliferation of injured carotid artery in diabetic rats 査読

    T Matsuoka, J Wada, Hashimoto, I, YL Zhang, J Eguchi, N Ogawa, K Shikata, YS Kanwar, H Makino

    DIABETES   54 ( 10 )   2882 - 2890   2005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)  

    DOI: 10.2337/diabetes.54.10.2882

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  • Renal-specific oxidoreductase biphasic expression under high glucose ambience during fetal versus neonatal development 査読

    YS Kanwar, S Akagi, B Nayak, L Sun, J Wada, P Xie, A Thakur, SS Chugh, FR Danesh

    KIDNEY INTERNATIONAL   68 ( 4 )   1670 - 1683   2005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)  

    DOI: 10.1111/j.1523-1755.2005.00611.x

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  • Clinical features of non-diabetic renal diseases in patients with type 2 diabetes 査読

    A Tone, K Shikata, M Matsuda, H Usui, S Okada, D Ogawa, J Wada, H Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   69 ( 3 )   237 - 242   2005年9月

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  • Hyperglycemia: its imminent effects on mammalian nephrogenesis 査読

    YS Kanwar, B Nayak, S Lin, S Akagi, P Xie, J Wada, SS Chugh, FR Danesh

    PEDIATRIC NEPHROLOGY   20 ( 7 )   858 - 866   2005年7月

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  • Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity 査読

    K Hida, J Wada, J Eguchi, H Zhang, M Baba, A Seida, L Hashimoto, T Okada, A Yasuhara, A Nakatsuka, K Shikata, S Hourai, J Futami, E Watanabe, Y Matsuki, R Hiramatsu, S Akagi, H Makino, YS Kanwar

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   102 ( 30 )   10610 - 10615   2005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)  

    DOI: 10.1073/pnas.0504703102

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  • Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity 査読

    J Eguchi, J Wada, K Hida, H Zhang, T Matsuoka, M Baba, Hashimoto, I, K Shikata, N Ogawa, H Makino

    BIOCHEMICAL JOURNAL   387   343 - 353   2005年4月

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    DOI: 10.1042/BJ20041709

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  • Cell biology of diabetic kidney disease

    Kanwar, YS, Akagi, S, Sun, L, Nayak, B

    Nephron Experimental Nephrology   101 ( 3 )   2005年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000087339

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  • Sulfated hyaluronic acid, a potential selectin inhibitor, ameliorates experimentally induced crescentic glomerulonephritis 査読

    D Ogawa, K Shikata, M Matsuda, K Akima, M Iwahashi, S Okada, Y Tsuchiyama, Y Shikata, J Wada, H Makino

    NEPHRON EXPERIMENTAL NEPHROLOGY   99 ( 1 )   E26 - E32   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000081795

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  • Pathological roles of advanced glycation end product receptors SR-A and CD36 査読

    S Horiuchi, Y Unno, H Usui, K Shikata, K Takaki, W Koita, YI Sakamoto, R Nagai, K Makino, A Sasao, J Wada, H Makino

    MAILLARD REACTION: CHEMISTRY AT THE INTERFACE OF NUTRITION, AGING, AND DISEASE   1043   671 - 675   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1196/annals.1333.076

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  • Cell biology of diabetic kidney disease

    Kanwar, Y.S., Akagi, S., Sun, L., Nayak, B., Xie, P., Wada, J., Chugh, S.S., Danesh, F.R.

    Nephron - Experimental Nephrology   101 ( 3 )   2005年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000087339

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  • The critical role of Src homology domain 2-containing tyrosine phosphatase-1 in recombinant human erythropoietin hyporesponsive anemia in chronic hemodialysis patients 査読

    S Akagi, H Ichikawa, T Okada, A Sarai, T Sugimoto, H Morimoto, T Kihara, A Yano, K Nakao, Y Nagake, J Wada, H Makino

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   15 ( 12 )   3215 - 3224   2004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)  

    DOI: 10.1097/01.ASN.0000145457.73744.24

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  • Changes in serum leptin concentrations in overweight Japanese men after exercise 査読

    N Miyatake, K Takahashi, J Wada, H Nishikawa, A Morishita, H Suzuki, M Kunitomi, H Makino, S Kira, M Fujii

    DIABETES OBESITY & METABOLISM   6 ( 5 )   332 - 337   2004年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1462-8902.2004.00351.x

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  • Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis 査読

    YS Kanwar, J Wada, S Lin, FR Danesh, SS Chugh, QW Yang, T Banerjee, JW Lomasney

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   286 ( 2 )   F202 - F215   2004年2月

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  • The role of adrenomedullin and receptors in glomerular hyperfiltration in streptozotocin-induced diabetic rats 査読

    K Hiragushi, J Wada, J Eguchi, T Matsuoka, A Yasuhara, Hashimoto, I, T Yamashita, K Hida, Y Nakamura, K Shikata, N Minamino, K Kangawa, H Makino

    KIDNEY INTERNATIONAL   65 ( 2 )   540 - 550   2004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)  

    DOI: 10.1111/j.1523-1755.2004.00407.x

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  • Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction 査読

    D Ogawa, K Shikata, K Honke, S Sato, M Matsuda, R Nagase, A Tone, S Okada, H Usui, J Wada, M Miyasaka, H Kawashima, Y Suzuki, T Suzuki, N Taniguchi, Y Hirahara, K Tadano-Aritomi, Ishizuka, I, TF Tedder, H Makino

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 3 )   2085 - 2090   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.M305809200

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  • Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion: Does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury? 査読

    A Seida, J Wada, Y Morita, M Baba, J Eguchi, N Nishimoto, T Okino, K Ichimura, T Yoshino, H Makino

    AMERICAN JOURNAL OF KIDNEY DISEASES   43 ( 1 )   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1053/j.ajkd.2003.09.023

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  • Intravenous vitamin D therapy reduces PTH-(1-84)/large C fragments ratio in chronic hemodialysis patients 査読

    T Kihara, H Ichikawa, H Morimoto, A Yano, S Akagi, K Nakao, H Kohmoto, J Wada, Kumagai, I, H Makino

    NEPHRON CLINICAL PRACTICE   98 ( 3 )   C93 - C100   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000080680

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  • Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion: does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury?

    Seida, A., Wada, J., Morita, Y., Baba, M., Eguchi, J., Nishimoto, N., Okino, T., Ichimura, K., Yoshino, T., Makino, H.

    American journal of kidney diseases : the official journal of the National Kidney Foundation   43 ( 1 )   2004年

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  • Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men 査読

    N Miyatake, K Takahashi, J Wada, H Nishikawa, A Morishita, H Suzuki, M Kunitomi, H Makino, S Kira, M Fujii

    DIABETES RESEARCH AND CLINICAL PRACTICE   62 ( 3 )   149 - 157   2003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)  

    DOI: 10.1016/S0168-8227(03)00176-1

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  • Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education 査読

    A Seida, J Wada, M Kunitomi, Y Tsuchiyama, N Miyatake, M Fujii, S Kira, K Takahashi, K Shikata, H Makino

    INTERNATIONAL JOURNAL OF OBESITY   27 ( 11 )   1325 - 1331   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/sj.ijo.0802408

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  • Pathogenesis of IgA nephropathy 査読

    J Wada, H Sugiyama, H Makino

    SEMINARS IN NEPHROLOGY   23 ( 6 )   556 - 563   2003年11月

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  • Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes 査読

    S Okada, K Shikata, M Matsuda, D Ogawa, H Usui, Y Kido, R Nagase, J Wada, Y Shikata, H Makino

    DIABETES   52 ( 10 )   2586 - 2593   2003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)  

    DOI: 10.2337/diabetes.52.10.2586

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  • Pelvic lymphocyst infection associated with maternally inherited diabetes mellitus 査読

    D Ogawa, K Shikata, M Matsuda, J Wada, H Uchida, M Asada, H Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   61 ( 2 )   137 - 141   2003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)  

    DOI: 10.1016/S0168-8227(03)00120-7

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  • Gene regulation of aldose-, aldehyde- and a renal specific oxido reductase (RSOR) in the pathobiology of diabetes mellitus 査読

    FR Danesh, J Wada, EI Wallner, A Sahai, SK Srivastava, YS Kanwar

    CURRENT MEDICINAL CHEMISTRY   10 ( 15 )   1399 - 1406   2003年8月

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  • Remission and regression of diabetic nephropathy 査読

    H Makino, Y Nakamura, J Wada

    HYPERTENSION RESEARCH   26 ( 7 )   515 - 519   2003年7月

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  • Glomerular cell apoptosis in human lupus nephritis 査読

    H Makino, H Sugiyama, Y Yamasaki, Y Maeshima, J Wada, N Kashihara

    VIRCHOWS ARCHIV   443 ( 1 )   67 - 77   2003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)  

    DOI: 10.1007/s00428-003-0827-x

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  • Successful treatment of necrotizing fasciitis associated with diabetic nephropathy 査読

    D Ogawa, K Shikata, J Wada, M Matsuda, H Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   60 ( 3 )   213 - 216   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/S0168-8227(03)00034-2

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  • Imprinted mesodermal specific transcript (MEST) and H19 genes in renal development and diabetes 査読

    YS Kanwar, XM Pan, S Lin, A Kumar, J Wada, CS Haas, G Liau, JW Lomasney

    KIDNEY INTERNATIONAL   63 ( 5 )   1658 - 1670   2003年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1046/j.1523-1755.2003.00905.x

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  • Perturbation of autocrine/paracrine loops of burst-forming units of erythroid-derived cells in rHuEPO-hyporesponsive hemodialysis patients 査読

    K Nakao, J Wada, K Ota, H Ichikawa, S Akagi, A Okamoto, K Hida, Y Nagake, H Makino

    AMERICAN JOURNAL OF KIDNEY DISEASES   41 ( 3 )   624 - 636   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1053/ajkd.2003.50124

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  • HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats 査読

    H Usui, K Shikata, M Matsuda, S Okada, D Ogawa, T Yamashita, K Hida, M Satoh, J Wada, H Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   18 ( 2 )   265 - 272   2003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)  

    DOI: 10.1093/ndt/18.2.265

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  • Erratum: HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats (Nephrology Dialysis Transplantation (2003) vol. 18 (265-272))

    Usui, H., Shikata, K., Matsuda, M., Okada, S., Ogawa, D., Yamashita, T., Hida, K., Satoh, M., Wada, J., Makino, H.

    Nephrology Dialysis Transplantation   18 ( 7 )   1418 - 1418   2003年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/ndt/gfg337

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  • Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats 査読

    D Ogawa, K Shikata, M Matsuda, S Okada, H Usui, J Wada, N Taniguchi, H Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   17 ( 12 )   2117 - 2121   2002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)  

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  • Daily walking reduces visceral adipose tissue areas and improves insulin resistance in Japanese obese subjects 査読

    N Miyatake, H Nishikawa, A Morishita, M Kunitomi, J Wada, H Suzuki, K Takahashi, H Makino, S Kira, M Fujii

    DIABETES RESEARCH AND CLINICAL PRACTICE   58 ( 2 )   101 - 107   2002年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/S0168-8227(02)00129-8

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  • Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis 査読

    M Matsuda, K Shikata, F Shimizu, Y Suzuki, M Miyasaka, H Kawachi, H Kawashima, J Wada, H Sugimoto, Y Shikata, D Ogawa, SJ Tojo, K Akima, H Makino

    JOURNAL OF PATHOLOGY   198 ( 3 )   407 - 414   2002年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/path.1209

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  • Beraprost sodium, prostacyclin analogue, attenuates glomerular hyperfiltration and glomerular macrophage infiltration by modulating ecNOS expression in diabetic rats 査読

    T Yamashita, K Shikata, M Matsuda, S Okada, D Ogawa, H Sugimoto, J Wada, H Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   57 ( 3 )   149 - 161   2002年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/S0168-8227(02)00054-2

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  • A case of congenital generalized lipodystrophy with lipoatrophic diabetes developing anti-insulin antibodies 査読

    H Usui, K Shikata, J Wada, T Sugimoto, J Yamana, T Oishi, M Matsuda, M Yoneda, Koshima, I, H Makino

    DIABETIC MEDICINE   19 ( 9 )   794 - 795   2002年9月

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  • Isolation and functional analysis of mouse UbA52 gene and its relevance to diabetic nephropathy 査読

    L Sun, XM Pan, J Wada, CS Haas, RP Wuthrich, FR Danesh, SS Chugh, YS Kanwar

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 33 )   29953 - 29962   2002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)  

    DOI: 10.1074/jbc.M204665200

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  • Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis 査読

    D Ogawa, K Shikata, M Matsuda, S Okada, J Wada, S Yamaguchi, Y Suzuki, M Miyasaka, S Tojo, H Makino

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   129 ( 1 )   43 - 53   2002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)  

    DOI: 10.1046/j.1365-2249.2002.01875.x

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  • Identification of developmentally regulated mesodermal-specific transcript in mouse embryonic metanephros 査読

    YS Kanwar, A Kumar, K Ota, S Lin, J Wada, S Chugh, EI Wallner

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   282 ( 5 )   F953 - F965   2002年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajprenal.00200.2001

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  • Minimal change nephrotic syndrome developing during postoperative interferon-beta therapy for malignant melanoma 査読

    K Nakao, H Sugiyama, E Makino, H Matsuura, A Ohmoto, T Sugimoto, H Ichikawa, J Wada, Y Yamasaki, H Makino

    NEPHRON   90 ( 4 )   498 - 500   2002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)  

    DOI: 10.1159/000054740

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  • Relevance of renal-specific oxidoreductase in tubulogenesis during mammalian nephron development 査読

    YS Kanwar, QW Yang, YF Tian, S Lin, J Wada, S Chugh, SK Srivastava

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   282 ( 4 )   F752 - F762   2002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)  

    DOI: 10.1152/ajprenal.00181.2001

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  • Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men 査読

    M Kunitomi, J Wada, K Takahashi, Y Tsuchiyama, Y Mimura, K Hida, N Miyatake, M Fujii, S Kira, K Shikata, H Makino

    INTERNATIONAL JOURNAL OF OBESITY   26 ( 3 )   361 - 369   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/sj/ijo/0801899

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  • Angiocentric immunoproliferative lesions of the lung associated with diffuse renal involvement 査読

    S Okada, J Wada, T Tsukinoki, N Hirano, Y Watanabe, K Shikata, Y Yamasaki, S Takase, T Yoshino, T Akagi, H Makino

    AMERICAN JOURNAL OF KIDNEY DISEASES   39 ( 3 )   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1053/ajkd.2002.31423

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  • Cyanotic congenital heart disease associated with glomerulomegaly and focal segmental glomerulosclerosis: Remission of nephrotic syndrome with angiotensin converting enzyme inhibitor 査読

    K Hida, J Wada, H Yamasaki, Y Nagake, H Zhang, H Sugiyama, K Shikata, H Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   17 ( 1 )   144 - 147   2002年1月

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  • Gene expression and identification of gene therapy targets in diabetic nephropathy 査読

    Jun Wada, Hirofumiand Makino, Yashpal S. Kanwar

    Kidney International   61 ( 1 )   S73 - S78   2002年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:Blackwell Publishing Inc.  

    DOI: 10.1046/j.1523-1755.2002.0610s1073.x

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  • Relevance of extracellular matrix and its receptors in mammalian nephrogenesis revealed by metanephric organ culture system 査読

    J Wada, YS Kanwar, H Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   17   75 - 77   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Renal gene expression in embryonic and newborn diabetic mice 査読

    EI Wallner, J Wada, S Lin, XM Pan, JK Reddy, SS Chugh, YS Kanwar

    EXPERIMENTAL NEPHROLOGY   10 ( 2 )   130 - 138   2002年

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  • Identification of developmentally regulated mesodermal-specific transcript in mouse embryonic metanephros 査読

    Yashpal S. Kanwar, Anil Kumar, Kosuke Ota, Sun Lin, Jun Wada, Sumant Chugh, Elisabeth I. Wallner

    American Journal of Physiology - Renal Physiology   282 ( 5 )   F953 - F965   2002年

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  • Relevance of renal-specific oxidoreductase in tubulogenesis during mammalian nephron development 査読

    Yashpal S. Kanwar, Qiwei Yang, Yufeng Tian, Sun Lin, Jun Wada, Sumant Chugh, Satish K. Srivastava

    American Journal of Physiology - Renal Physiology   282 ( 4 )   F752 - F762   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • History of nephrology in the past 100 years: Collagen disease and vasculitis

    Makino, H., Wada, J.

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   91 ( 5 )   2002年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/naika.91.1492

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  • Angiocentric immunoproliferative lesions of the lung associated with diffuse renal involvement.

    Okada, S., Wada, J., Tsukinoki, T., Hirano, N., Watanabe, Y., Shikata, K., Yamasaki, Y., Takase, S., Yoshino, T., Akagi, T., Makino, H.

    American journal of kidney diseases : the official journal of the National Kidney Foundation   39 ( 3 )   2002年

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  • Management of diabetic nephropathy with nephrotic syndrome

    Eguchi, J., Wada, J., Makino, H.

    Nippon rinsho. Japanese journal of clinical medicine   60 Suppl 10   2002年

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  • Proteoglycans

    Makino, H., Wada, J.

    Nippon rinsho. Japanese journal of clinical medicine   60 Suppl 8   2002年

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  • Identification of up-regulated Ras-like GTPase, Rap1b, by suppression subtractive hybridization 査読

    S Lin, S Chugh, XM Pan, EI Wallner, J Wada, YS Kanwar

    KIDNEY INTERNATIONAL   60 ( 6 )   2129 - 2141   2001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)  

    DOI: 10.1046/j.1523-1755.2001.00061.x

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  • Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes 査読

    K Hiragushi, H Sugimoto, K Shikata, T Yamashita, N Miyatake, Y Shikata, J Wada, Kumagai, I, M Fukushima, H Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   53 ( 3 )   149 - 159   2001年9月

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    DOI: 10.1016/S0168-8227(01)00260-1

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  • Ultrastructure of glomerular basement membrane in active Heymann nephritis rats revealed by tissue-negative staining method 査読

    Y Hayashi, K Hironaka, K Shikata, S Ogawa, K Ota, J Wada, K Kamata, Z Ota, H Makino

    AMERICAN JOURNAL OF NEPHROLOGY   21 ( 3 )   249 - 255   2001年5月

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    DOI: 10.1159/000046257

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  • Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys 査読

    H Zhang, J Wada, K Hida, Y Tsuchiyama, K Hiragushi, K Shikata, HY Wang, S Lin, YS Kanwar, H Makino

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 20 )   17132 - 17139   2001年5月

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    DOI: 10.1074/jbc.M006723200

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  • Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis 査読

    J Wada, H Zhang, Y Tsuchiyama, K Hiragushi, K Hida, K Shikata, YS Kanwar, H Makino

    KIDNEY INTERNATIONAL   59 ( 4 )   1363 - 1373   2001年4月

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    DOI: 10.1046/j.1523-1755.2001.0590041363.x

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  • Galectins, galactoside-binding mammalian lectins: Clinical application of multi-functional proteins 査読

    J Wada, H Makino

    ACTA MEDICA OKAYAMA   55 ( 1 )   11 - 17   2001年2月

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  • Status of glucose transporters in the mammalian kidney and renal development 査読

    EI Wallner, J Wada, G Tramonti, S Lin, YS Kanwar

    RENAL FAILURE   23 ( 3-4 )   301 - 310   2001年

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    DOI: 10.1081/JDI-100104714

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  • Relevance of aldo-keto reductase family members to the pathobiology of diabetic nephropathy and renal development 査読

    EI Wallner, J Wada, G Tramonti, S Lin, SK Srivastava, YS Kanwar

    RENAL FAILURE   23 ( 3-4 )   311 - 320   2001年

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    DOI: 10.1081/JDI-100104715

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  • Diagnosis and treatment of diabetic nephropathy

    Makino, H., Shikata, K., Wada, J.

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   90 ( 2 )   2001年

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    DOI: 10.2169/naika.90.350

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  • The necessity of renal biopsies in the management of diabetic nephropathy

    Makino, H., Wada, J., Matsuda, M.

    Internal Medicine   40 ( 11 )   2001年

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    DOI: 10.2169/internalmedicine.40.1071

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  • Successful use of cyclosporin A for the treatment of acute interstitial pneumonitis associated with rheumatoid arthritis 査読

    D Ogawa, H Hashimoto, J Wada, A Ueno, Y Yamasaki, M Yamamura, H Makino

    RHEUMATOLOGY   39 ( 12 )   1422 - 1424   2000年12月

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  • Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats 査読

    Y Tsuchiyama, J Wada, H Zhang, Y Morita, K Hiragushi, K Hida, K Shikata, M Yamamura, YS Kanwar, H Makino

    KIDNEY INTERNATIONAL   58 ( 5 )   1941 - 1952   2000年11月

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    DOI: 10.1046/j.1523-1755.2000.00366.x

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  • Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats 査読

    K Hida, J Wada, H Zhang, K Hiragushi, Y Tsuchiyama, K Shikata, H Makino

    JOURNAL OF LIPID RESEARCH   41 ( 10 )   1615 - 1622   2000年10月

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  • Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold 査読

    M Kunitomi, K Takahashi, J Wada, H Suzuki, N Miyatake, S Ogawa, S Ohta, H Sugimoto, K Shikata, H Makino

    DIABETES RESEARCH AND CLINICAL PRACTICE   50 ( 2 )   109 - 115   2000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)  

    DOI: 10.1016/S0168-8227(00)00170-4

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  • Expression characteristics and relevance of sodium glucose cotransporter-1 in mammalian renal tubulogenesis 査読

    QW Yang, YF Tian, J Wada, N Kashihara, E Wallner, D Peterson, YS Kanwar

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   279 ( 4 )   F765 - F777   2000年10月

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  • Familial interstitial nephritis with progressive renal failure 査読

    H Zhang, J Wada, K Nanba, M Kunitomi, K Hida, Y Nagake, K Shikata, H Makino

    AMERICAN JOURNAL OF KIDNEY DISEASES   36 ( 4 )   art. no. - e25   2000年10月

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    DOI: 10.1053/ajkd.2000.17730

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  • Identification of a renal-specific oxido-reductase in newborn diabetic mice 査読

    QW Yang, B Dixit, J Wada, YF Tian, EI Wallner, SK Srivastva, YS Kanwar

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   97 ( 18 )   9896 - 9901   2000年8月

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    DOI: 10.1073/pnas.160266197

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  • Clinical evaluation of muscle strength in 20-79-years-old obese Japanese 査読

    N Miyatake, M Fujii, H Nishikawa, J Wada, K Shikata, H Makino, Kimura, I

    DIABETES RESEARCH AND CLINICAL PRACTICE   48 ( 1 )   15 - 21   2000年4月

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    DOI: 10.1016/S0168-8227(99)00132-1

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  • Malignant hypertension with a rare complication of pulmonary alveolar hemorrhage 査読

    K Hida, J Wada, M Odawara, M Kunitomi, N Hayakawa, N Kashihara, H Makino

    AMERICAN JOURNAL OF NEPHROLOGY   20 ( 1 )   64 - 67   2000年1月

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    DOI: 10.1159/000013558

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  • Fatal pancreatitis associated with systemic amyloidosis in a rheumatoid arthritis patient 査読

    Kazuhiro Oishi, Jun Wada, Yoshio Nagake, Kazuyuki Hida, Hiroo Hashimoto, Nobuaki Hayakawa, Naoki Kashihara, Hirofumi Makino

    Journal of Medicine   31 ( 5-6 )   303 - 310   2000年

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  • Familial interstitial nephritis with progressive renal failure.

    Zhang, H., Wada, J., Nanba, K., Kunitomi, M., Hida, K., Nagake, Y., Shikata, K., Makino, H.

    American journal of kidney diseases : the official journal of the National Kidney Foundation   36 ( 4 )   2000年

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  • Role of membrane-type matrix metalloproteinase 1 (MT-1-MMP), MMP-2, and its inhibitor in nephrogenesis 査読

    YS Kanwar, K Ota, QW Yang, J Wada, N Kashihara, Y Tian, EI Wallner

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   277 ( 6 )   F934 - F947   1999年12月

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  • Novel approaches to unravel the genesis of glomerulosclerosis by new methodologies in molecular biology and molecular genetics 査読

    J Wada, K Shikata, H Makino

    NEPHROLOGY DIALYSIS TRANSPLANTATION   14 ( 11 )   2551 - 2553   1999年11月

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  • Tubulointerstitial nephritis antigen: An extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development 査読

    YS Kanwar, A Kumar, QW Yang, YF Tian, J Wada, N Kashihara, EI Wallner

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   96 ( 20 )   11323 - 11328   1999年9月

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    DOI: 10.1073/pnas.96.20.11323

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  • Integrins mediate the inhibitory effect of focal adhesion on angiotensin II-induced p44/42 mitogen-activated protein (MAP) kinase activity in human mesangial cells 査読

    Y Shikata, K Shikata, M Matsuda, K Hiragushi, D Ogawa, H Sugimoto, J Wada, H Makino

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   261 ( 3 )   820 - 823   1999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)  

    DOI: 10.1006/bbrc.1999.1080

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  • Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung 査読

    QW Yang, K Ota, YF Tian, A Kumar, J Wada, N Kashihara, E Wallner, YS Kanwar

    DEVELOPMENTAL BIOLOGY   212 ( 1 )   229 - 242   1999年8月

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    DOI: 10.1006/dbio.1999.9331

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  • Screening for genes up-regulated in 5/6 nephrectomized mouse kidney 査読

    H Zhang, J Wada, YS Kanwar, Y Tsuchiyama, K Hiragushi, K Hida, K Shikata, H Makino

    KIDNEY INTERNATIONAL   56 ( 2 )   549 - 558   1999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)  

    DOI: 10.1046/j.1523-1755.1999.00561.x

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  • Advanced glycation end products-cytokine-nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumour necrosis factor-alpha and inducible nitric oxide synthase in diabetic rat glomeruli 査読

    H Sugimoto, K Shikata, J Wada, S Horiuchi, H Makino

    DIABETOLOGIA   42 ( 7 )   878 - 886   1999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)  

    DOI: 10.1007/s001250051241

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  • L-selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction 査読

    K Shikata, Y Suzuki, J Wada, K Hirata, M Matsuda, H Kawashima, T Suzuki, M Iizuka, H Makino, M Miyasaka

    JOURNAL OF PATHOLOGY   188 ( 1 )   93 - 99   1999年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/(SICI)1096-9896(199905)188:1<93::AID-PATH305>3.0.CO;2-#

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  • Signaling transduction pathway of angiotensin II in human mesangial cells: Mediation of focal adhesion and GTPase activating proteins 査読

    Y Shikata, K Shikata, M Masuda, H Sugimoto, J Wada, H Makino

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   257 ( 1 )   234 - 238   1999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)  

    DOI: 10.1006/bbrc.1999.0441

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  • Differential distribution of insulin-like growth factor-1 and insulin-like growth factor binding proteins in experimental diabetic rat kidney 査読

    N Miyatake, K Shikata, J Wada, H Sugimoto, S Takahashi, H Makino

    NEPHRON   81 ( 3 )   317 - 323   1999年3月

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  • Increased urinary excretion of macrophage-colony-stimulating factor (M-CSF) in patients with IgA nephropathy: Tonsil stimulation enhances urinary M-CSF excretion 査読

    M Matsuda, K Shikata, J Wada, H Yamaji, Y Shikata, A Doi, M Kosaka, H Akagi, Y Masuda, Y Ohmoto, H Makino

    NEPHRON   81 ( 3 )   264 - 270   1999年3月

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  • Renal organogenesis and extracellular matrix - Knockout mice are telling the truth? -

    Wada, J., Ota, K., Kashihara, N., Kanwar, Y.S., Makino, H.

    Connective Tissue   31 ( 1 )   1999年

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  • Increased expression of endothelial cell nitric oxide synthase (ecNOS) in afferent and glomerular endothelial cells is involved in glomerular hyperfiltration of diabetic nephropathy 査読

    H Sugimoto, K Shikata, M Matsuda, M Kushiro, Y Hayashi, K Hiragushi, J Wada, H Makino

    DIABETOLOGIA   41 ( 12 )   1426 - 1434   1998年12月

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    DOI: 10.1007/s001250051088

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  • Deposition of mannan binding protein and mannan binding protein-mediated complement activation in the glomeruli of patients with IgA nephropathy 査読

    M Matsuda, K Shikata, J Wada, H Sugimoto, Y Shikata, T Kawasaki, H Makino

    NEPHRON   80 ( 4 )   408 - 413   1998年12月

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  • Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development 査読

    YS Kanwar, K Ota, QW Yang, A Kumar, J Wada, N Kashihara, DR Peterson

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   275 ( 5 )   F710 - F723   1998年11月

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  • Relevance of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis 査読

    EI Wallner, QW Yang, DR Peterson, J Wada, YS Kanwar

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   275 ( 4 )   F467 - F477   1998年10月

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  • A case of membranous nephropathy associated with psoriasis vulgaris 査読

    H Yamaji, K Shikata, J Wada, Y Hayashi, S Ikeda, H Makino

    NEPHRON   80 ( 1 )   111 - 112   1998年9月

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  • Fatal hyperammonemia in a patient with systemic lupus erythematosus 査読

    H Ichikawa, T Amano, K Kawabata, M Kushiro, J Wada, Y Nagake, H Makino

    INTERNAL MEDICINE   37 ( 8 )   700 - 703   1998年8月

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    DOI: 10.2169/internalmedicine.37.700

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  • Ultrastructure of mesangial type III collagen deposition in a patient with IgA nephropathy 査読

    M Kunitomi, J Wada, N Miyatake, Y Hayashi, K Ota, H Makino

    AMERICAN JOURNAL OF KIDNEY DISEASES   32 ( 1 )   146 - 152   1998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)  

    DOI: 10.1053/ajkd.1998.v32.pm9669436

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  • Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor 査読

    K Ota, WG Stetler-Stevenson, QW Yang, A Kumar, J Wada, N Kashihara, EI Wallner, YS Kanwar

    KIDNEY INTERNATIONAL   54 ( 1 )   131 - 142   1998年7月

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  • Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat 査読

    M Kushiro, K Shikata, H Sugimoto, Y Shikata, N Miyatake, J Wada, M Miyasaka, H Makino

    KIDNEY INTERNATIONAL   53 ( 5 )   1314 - 1320   1998年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1046/j.1523-1755.1998.00881.x

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  • Characterization of mammalian translocase of inner mitochondrial membrane (Tim44) isolated from diabetic newborn mouse kidney 査読

    J Wada, YS Kanwar

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   95 ( 1 )   144 - 149   1998年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1073/pnas.95.1.144

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  • Bcl-2 expression and apoptosis in nephrotoxic nephritis 査読

    H Sugiyama, N Kashihara, T Onbe, Y Yamasaki, J Wada, T Sekikawa, K Okamoto, K Kanao, Y Maeshima, H Makino

    EXPERIMENTAL NEPHROLOGY   5 ( 6 )   481 - 489   1997年11月

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  • Role of extracellular matrix, growth factors and proto-oncogenes in metanephric development 査読

    YS Kanwar, FA Carone, A Kumar, J Wada, K Ota, EI Wallner

    KIDNEY INTERNATIONAL   52 ( 3 )   589 - 606   1997年9月

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  • Developmental regulation and partial-length cloning of tubulointerstitial nephritis antigen of murine metanephros 査読

    A Kumar, K Ota, J Wada, EI Wallner, AS Charonis, FA Carone, YS Kanwar

    KIDNEY INTERNATIONAL   52 ( 3 )   620 - 627   1997年9月

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  • Representational difference analysis of cDNA of genes expressed in embryonic kidney 査読

    J Wada, A Kumar, K Ota, EI Wallner, DC Batlle, YS Kanwar

    KIDNEY INTERNATIONAL   51 ( 5 )   1629 - 1638   1997年5月

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  • Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin 査読

    J Wada, K Ota, A Kumar, EI Wallner, YS Kanwar

    JOURNAL OF CLINICAL INVESTIGATION   99 ( 10 )   2452 - 2461   1997年5月

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    DOI: 10.1172/jci119429

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  • Identification and characterization of galectin-9, a novel beta-galactoside-binding mammalian lectin 査読

    J Wada, YS Kanwar

    JOURNAL OF BIOLOGICAL CHEMISTRY   272 ( 9 )   6078 - 6086   1997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)  

    DOI: 10.1074/jbc.272.9.6078

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  • D-glucose-induced dysmorphogenesis of embryonic kidney 査読

    YS Kanwar, ZZ Liu, A Kumar, MI Usman, J Wada, EI Wallner

    JOURNAL OF CLINICAL INVESTIGATION   98 ( 11 )   2478 - 2488   1996年12月

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  • Comparative role of phosphotyrosine kinase domains of c-ros and c-ret protooncogenes in metanephric development with respect to growth factors and matrix morphogens 査読

    ZZ Liu, J Wada, A Kumar, FA Carone, M Takahashi, YS Kanwar

    DEVELOPMENTAL BIOLOGY   178 ( 1 )   133 - 148   1996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)  

    DOI: 10.1006/dbio.1996.0204

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  • The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats 査読

    J Wada, K Shikata, H Makino, S Morioka, K Hirata, K Ota, T Tamatani, M Miyasaka, T Horiuchi, S Noji, K Nishikawa, F Myokai, S Taniguchi, YS Kanwar, Z Ota

    NEPHRON   73 ( 2 )   264 - 272   1996年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Cloning of mouse integrin alpha(V) cDNA and role of the alpha(V)-related matrix receptors in metanephric development 査読

    J Wada, A Kumar, Z Liu, E Ruoslahti, L Reichardt, J Marvaldi, YS Kanwar

    JOURNAL OF CELL BIOLOGY   132 ( 6 )   1161 - 1176   1996年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1083/jcb.132.6.1161

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  • The Critical Role of Intercellular Adhesion Molecule-1 in Masugi Nephritis in Rats

    Jun Wada

    Nephron Clinical Practice   73 ( 2 )   1996年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000189050

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  • Erratum: Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins (Kidney Int (48: 1646-1659))

    Kanwar, Y.S., Liu, Z.Z., Kumar, A., Wada, J., Carone, F.A.

    Kidney International   49 ( 1 )   306 - 306   1996年

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    掲載種別:研究論文(学術雑誌)  

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  • CLONING OF MOUSE C-ROS RENAL CDNA, ITS ROLE IN DEVELOPMENT AND RELATIONSHIP TO EXTRACELLULAR-MATRIX GLYCOPROTEINS 査読

    YS KANWAR, ZZ LIU, A KUMAR, J WADA, FA CARONE

    KIDNEY INTERNATIONAL   48 ( 5 )   1646 - 1659   1995年11月

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    記述言語:英語  

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  • DISTRIBUTION OF EXTRACELLULAR-MATRIX RECEPTORS IN VARIOUS FORMS OF GLOMERULONEPHRITIS 査読

    K SHIKATA, H MAKINO, S MORIOKA, T KASHITANI, K HIRATA, Z OTA, J WADA, YS KANWAR

    AMERICAN JOURNAL OF KIDNEY DISEASES   25 ( 5 )   680 - 688   1995年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A case of systemic lupus erythematosus associated with severe fibrinoid necrosis located mainly in the glomerular afferent arteriole

    Morioka, S., Makino, H., Wada, J., Shikata, K., Yamasaki, Y., Ogura, T., Amano, T., Asaumi, A., Okada, S., Ota, Z.

    The Japanese Journal of Nephrology   37 ( 1 )   1995年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.14842/jpnjnephrol1959.37.69

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  • Activation of complement during hemodialysis

    Nagake, Y., Amano, T., Wada, J., Sugimoto, H., Kawabata, K., Shikata, K., Makino, H., Ota, Z.

    Japanese Journal of Clinical Immunology   18 ( 2 )   1995年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2177/jsci.18.138

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  • TROPHIC EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I ON METANEPHRIC DEVELOPMENT - RELATIONSHIP TO PROTEOGLYCANS 査読

    ZZ LIU, A KUMAR, EI WALLNER, J WADA, FA CARONE, YS KANWAR

    EUROPEAN JOURNAL OF CELL BIOLOGY   65 ( 2 )   378 - 391   1994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)  

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  • LOCALIZATION OF FIBRIL MICROFIBRIL AND BASEMENT-MEMBRANE COLLAGENS IN DIABETIC GLOMERULOSCLEROSIS IN TYPE-2 DIABETES 査読

    H MAKINO, K SHIKATA, J WIESLANDER, J WADA, N KASHIHARA, K YOSHIOKA, Z OTA

    DIABETIC MEDICINE   11 ( 3 )   304 - 311   1994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)  

    DOI: 10.1111/j.1464-5491.1994.tb00276.x

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  • IMMUNOREACTIVITY OF THE JK-132 MONOCLONAL-ANTIBODY DIRECTED AGAINST BASEMENT-MEMBRANE COLLAGEN IN NORMAL AND DIABETIC GLOMERULI 査読

    H MAKINO, K SHIKATA, T HAYASHI, J WIESLANDER, T HARAMOTO, K HIRATA, J WADA, T YOSHIDA, K YOSHIOKA, Z OTA

    VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY   424 ( 3 )   235 - 241   1994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)  

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  • INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR IN METANEPHRIC DEVELOPMENT 査読

    YS KANWAR, ZZ LIU, J WADA

    EXTRACELLULAR MATRIX IN THE KIDNEY   107   168 - 173   1994年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  • A case of non-IgA mesangioproliferative glomerulonephritis with huge paramesangial hemispherical deposits

    Sugimoto, H., Makino, H., Wada, J., Shikata, K.-I., Ikeda, S., Ota, Z.

    the japanese journal of nephrology   35 ( 9 )   1994年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.14842/jpnjnephrol1959.35.1091

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  • Effect of heparin and low-molecular-weight heparin on proliferative glomerulonephritis

    Morita, Y., Makino, H., Ota, K., Wada, J., Shikata, K., Kashihara, N., Ikeda, S., Ogura, T., Ota, Z.

    Japanese Journal of Nephrology   36 ( 7 )   1994年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.14842/jpnjnephrol1959.36.832

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  • DISTRIBUTION AND RELEVANCE OF INSULIN-LIKE GROWTH FACTOR-I RECEPTOR IN METANEPHRIC DEVELOPMENT 査読

    ZZ LIU, J WADA, K ALVARES, A KUMAR, EI WALLNER, YS KANWAR

    KIDNEY INTERNATIONAL   44 ( 6 )   1242 - 1250   1993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)  

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  • CLONING OF CDNA FOR THE ALPHA-SUBUNIT OF MOUSE INSULIN-LIKE GROWTH FACTOR-I RECEPTOR AND THE ROLE OF THE RECEPTOR IN METANEPHRIC DEVELOPMENT 査読

    J WADA, ZZ LIU, K ALVARES, A KUMAR, E WALLNER, H MAKINO, YS KANWAR

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   90 ( 21 )   10360 - 10364   1993年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1073/pnas.90.21.10360

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  • Expression of the VLA family of integrins in the renal glomerulus

    Makino, H., Shikata, K., Morioka, S., Wada, J., Ota, Z.

    Nihon Jinzo Gakkai Shi   35 ( 1 )   1993年

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  • Expression of the VLA Family of Integrins in the Renal Glomerulus

    Makino, H., Shikata, K., Morioka, S., Wada, J., Ota, Z.

    the japanese journal of nephrology   35 ( 1 )   1993年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.14842/jpnjnephrol1959.35.19

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  • Clinicopathological study of patients with immune complex type and pauci immune type rapidly progressive glomerulonephritis

    Sugiyama, H., Makino, H., Wada, J., Ota, K., Nagake, Y., Morioka, S., Yamasaki, Y., Shikata, K., Kashihara, N., Ikeda, S., Ogura, T., Ota, Z.

    Japanese Journal of Nephrology   35 ( 6 )   1993年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.14842/jpnjnephrol1959.35.777

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  • Immunohistochemical study of vitronectin and membrane attack complex in normal and diseased renal tissues

    Wada, J., Makino, H., Shikata, K., Morioka, S., Ota, Z.

    Connective Tissue   23 ( 2 )   1992年

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    掲載種別:研究論文(学術雑誌)  

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  • Distribution of a novel chain of basement membrane associated-collagen in the renal tissue

    Makino, H., Haramoto, T., Shikata, K., Hirata, K., Wada, J., Morioka, S., Ota, Z., Yoshida, T., Hayashi, T.

    Connective Tissue   24 ( 3 )   1992年

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    掲載種別:研究論文(学術雑誌)  

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  • Plasma concentrations of vitronectin in patients with glomerulonephritis

    Morioka, S., Makino, H., Shikata, K., Wada, J., Ota, Z., Uchida, M., Shimo-oka, T., Ii, I.

    Connective Tissue   23 ( 3-4 )   1992年

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    掲載種別:研究論文(学術雑誌)  

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  • Localization of fibronectin receptor and vitronectin receptor in the glomerulus - Comparison with their ligands

    Makino, H., Shikata, K., Morioka, S., Wada, J., Ota, Z.

    Connective Tissue   23 ( 2 )   1992年

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    掲載種別:研究論文(学術雑誌)  

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  • A case of neuro-Behçet's disease started with diplopia

    Wada, J., Amano, T., Tanokuchi, S., Ota, Z., Oshima, K., Otsuki, H., Matsuo, N.

    Japanese Journal of Clinical Immunology   14 ( 4 )   1991年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2177/jsci.14.463

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  • A case of lupus nephritis with hyporeninemic hypoaldosteronism

    Wada, J., Makino, H., Ota, Z., Yokoi, T., Nagayama, K., Asano, K., Fukushima, M.

    The Japanese Journal of Nephrology   33 ( 8 )   1991年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.14842/jpnjnephrol1959.33.817

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  • A Case of Idiopathic Diabetes Insipidus Complicated by Diabetes Mellitus

    Wada, J., Hashimoto, K., Takahashi, K., Kubota, A., Kusumoto, T., Miyake, Y.

    Journal of the Japan Diabetes Society   34 ( 11 )   1991年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.11213/tonyobyo1958.34.1007

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書籍等出版物

  • Chapter 3 Prominent insulin resistance in congenital generalized lipoatrophy, Ed Oohashi T, Tsukahara H, Ramirez F, Barber CL, Otsuka F, In Human Pahtobiochemistry

    Jun Wada, Yashpal S Kanwar

    Springer Nature Singapore  2019年 

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  • Chapter 12 Vaspin: Visceral Adipose Tissue-Derived Serpin with Insulin-Sensitizing Effects, Ed Bojidor Georgiev and Sava Markovski, In Serpins and Protein Kinase Inhibitors: Novel Functions, Structural Features and Molecular Mechanisms

    Jun Wada

    Nova Science Publishers, Hauppauge NY  2009年 

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  • Chapter 11 Protein sequence analysis, pp333-378, Ed Shui Qing Ye, In Bioinformatics, A practical Approach

    Jun Wada, Hiroko Tada, Masaharu Seno

    Chapman & Hall/CRC  2008年 

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    総ページ数:xxvi, 618 p.   記述言語:英語

    CiNii Books

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  • Chapter 18 Serpins and the metabolic syndrome, pp411-423, Ed Gary A. Silverman and David A. Lomas, In Molecular and cellular aspects of the serpinopathies and disorders in serpin activity

    Jun Wada

    World Scientific Publishing, Singapore  2007年 

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MISC

▼全件表示

産業財産権

  • 腎機能の低下の可能性を判定するための方法およびキット

    和田 淳, 三瀬 広記, 山田 雅雄

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    出願人:国立大学法人 岡山大学

    出願番号:特願2017-072324  出願日:2017年3月31日

    公開番号:特開2018-173371  公開日:2018年11月8日

    特許番号/登録番号:特許第6829440号  登録日:2021年1月26日 

    J-GLOBAL

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  • 免疫抑制剤および自己免疫疾患の予防および治療剤

    和田 淳, 神崎 資子, 八木田 秀雄, 棚井 丈雄

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    出願人:国立大学法人 岡山大学

    出願番号:特願2011-547342  出願日:2010年1月26日

    公表番号:特表2012-515766  公表日:2012年7月12日

    特許番号/登録番号:特許第5569946号  登録日:2014年7月4日 

    J-GLOBAL

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  • 糖尿病性腎症の進行度の検出方法及び糖尿病性腎症の進行度の診断キット並びに糖尿病性腎症の進行度の指標となる物質及びその選別方法

    和田 淳, 井上 謙太郎, 山田 雅雄, 小川 智央, 武石 俊作

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    出願人:国立大学法人 岡山大学

    出願番号:特願2009-105513  出願日:2009年4月23日

    公開番号:特開2010-256132  公開日:2010年11月11日

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  • 動脈硬化の予防・治療剤

    和田 淳, 槇野 博史, 松木 泰

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    出願人:国立大学法人 岡山大学

    出願番号:特願2007-079546  出願日:2007年3月26日

    公開番号:特開2008-239517  公開日:2008年10月9日

    特許番号/登録番号:特許第5076096号  登録日:2012年9月7日 

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  • 肥満の予防・治療剤

    和田 淳, 槇野 博史, 松木 泰

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    出願人:国立大学法人 岡山大学

    出願番号:特願2007-079547  出願日:2007年3月26日

    公開番号:特開2008-239518  公開日:2008年10月9日

    特許番号/登録番号:特許第5119510号  登録日:2012年11月2日 

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  • 糖尿病性腎症の予防・治療剤

    和田 淳, 槇野 博史, 馬場 雅子, 江口 潤

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    出願人:国立大学法人 岡山大学

    出願番号:特願2004-132275  出願日:2004年4月27日

    公開番号:特開2005-314252  公開日:2005年11月10日

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▼全件表示

受賞

  • 岡山市文化奨励賞

    2012年11月  

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  • 日本肥満学会学術奨励賞

    2009年  

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    受賞国:日本国

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  • 糖尿病合併症学会Young Investigator Award

    2002年  

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    受賞国:日本国

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  • 岡山医師会奨励賞

    2001年  

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    受賞国:日本国

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  • 岡山医学賞結城賞

    2001年  

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    受賞国:日本国

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共同研究・競争的資金等の研究

  • 尿レクチンアレイ解析を用いた腎疾患診断キットの開発

    2020年04月 - 2023年03月

    日本医療研究開発機構研究費  難治性疾患実用化研究事業  難治性疾患実用化研究事業

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    担当区分:研究代表者  資金種別:競争的資金

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  • 糖尿病性腎症における糖鎖異常とその病態的意義

    研究課題/領域番号:19H03675  2019年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    和田 淳

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    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

    特異性の異なる45種類のレクチンを用いた尿レクチンアレイ解析を開発した (PLoS ONE 8(10), e77118, 2013)。さらに平成24年度より2型糖尿病患者680例の4年間のコホート研究でベースラインのα2-6シアル酸関連レクチン(SNA)、Galβ1-3GalNAc (T-antigen)関連レクチン (ABA, Jacalin, ACA)、RCA120への結合シグナル高値が4年後のeGFR 30%低下の危険因子であることを報告した(Diabetes Care. 41(8), 1765-1775, 2018)。現在このコホート研究を継続しており、腎機能低下の予測マーカーとしての有用性の検証を続けている(Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy:U-CARE研究)。
    この2型糖尿病患者のコホート研究で、尿レクチンアレイ解析による糖鎖の網羅的解の結果から、尿中レクチン(SNA, ABA, Jacalin, ACA, RCA120)への結合シグナルの上昇が腎機能低下のリスクであることを見出したが、これらのレクチンが認識する糖鎖は糖タンパク質上のT-antigen, Tn-antigen, sialyl-T, sialyl-Tn, Core 3を認識しており、いずれも合成不全糖鎖であり癌組織において発現する抗原でもある。糖尿病モデル動物および腎生検で証明された糖尿病腎症患者の尿レクチンアレイ解析と腎組織のレクチン組織化学、腎組織におけるCore 2およびCore 4合成酵素であるGlucosaminyl (N-acetyl) transferase (GCNT1/3/4)などの糖鎖合成酵素の定量を行った。

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  • 尿中糖鎖プロファイリングによるIgA腎症の診断法の開発

    2017年04月

    医療研究開発推進事業費補助金  革新的医療シーズ実用化研究事業  革新的医療シーズ実用化研究事業

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:150211000円 ( 直接経費:115546924円 、 間接経費:34664076円 )

    慢性腎臓病(CKD)の患者数は、1,330万人に達し我が国の成人の8人に1人はCKDであり国民病といえる。2014年の新規透析導入患者36,377人のうち糖尿病腎症15,809人(43.5%)は横ばいで推移しており、腎硬化症5,151人(14.2%)、不明4,102人(11.3%)は一貫して増加傾向にある。一方慢性糸球体腎炎6,466人(17.8%)は漸減傾向が続いているが未だに重要な疾患である。
    腎疾患の確定診断には腎生検が用いられる。IgA腎症は腎生検による病理診断される疾患のうち最も多い。従来蛋白尿や血尿、尿沈渣の赤血球変形や顆粒円柱の存在が腎生検の適応とされている。しかしながら尿所見が軽微であったり一過性であることが多く腎生検に至らなかったり、また腎生検自体が患者への負担が大きく確定診断の障壁となっている。従ってIgA腎症に特異的なバイオマーカーの同定が喫緊の課題と考えられる。我々は先行研究において45種類のレクチンを用いた尿レクチンアレイ解析法の開発に成功し、特にIgA腎症において特異的な糖鎖プロファイリングが得られることが判明した。本研究ではさらにこの検査法による非侵襲的なIgA腎症の新規診断法の開発を目的とした臨床試験を実施する。
    腎生検で確定診断された種々の腎疾患(糖尿病腎症、IgA腎症、膜性増殖性糸球体腎炎、膜性腎症、微小変化ネフローゼ症候群、巣状分節性糸球体硬化症、ループス腎炎、高血圧性腎硬化症、肥満関連腎症、間質性腎炎、薬剤性腎障害)で後方視的に尿レクチンアレイを施行し、蛍光シグナル強度データの統計解析を実施して、IgA腎症に特異的な糖鎖プロファイリングを明らかにし、IgA腎症を鑑別するために必要な尿レクチンの選定および診断アルゴリズムの構成と診断閾の特定を行なう(Extant試験-後ろ向き-)。さらに腎生検を施行された症例に対して前向きに尿レクチンアレイを施行し、後ろ向き研究で構成した診断アルゴリズムの診断精度の評価とアルゴリズムの最終化を行ない、本検査法の体外診断薬としての有用性を検証する(Extant試験-前向き-)。この腎生検によらない診断法の開発により、早期の治療や腎生検が必要な患者のスクリーニングが可能となり、透析導入症例の大幅な減少が期待される。

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  • 全身性エリテマトーデスにおけるRAGE/HMGB1 Axisの病態的関与

    研究課題/領域番号:16K19600  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    渡辺 晴樹, 渡部 克枝, 佐田 憲映, 山本 博, 和田 淳

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    鉱物油成分であるプリスタンを腹腔内に投与すると炎症が引き起され腎炎や関節炎など全身性エリテマトーデス(SLE)に類似した症状が起こる。RAGE遺伝子を欠損させたマウスにプリスタンを投与したところ、RAGEを欠損させていないマウスと比較し生存率が改善する傾向にあり、これにはマクロファージという異物を捕食して消化し清掃屋の役割を果たす細胞の関与が考えられた。また別の自然発症SLEモデルであるMRL/lprマウスのRAGE遺伝子を欠損させたところ蛋白尿が減少し脾臓やリンパ節の重量も低下しており、RAGEがSLEの治療標的となる可能性が示された。

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  • メタボリックシンドロームにおける腎障害とVaspinの意義

    研究課題/領域番号:26461361  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中司 敦子, 和田 淳

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    我々はこれまでにアディポカインであるvaspinを同定し、vaspinが脂肪細胞から血中へ分泌され、インスリン抵抗性や肥満・脂肪肝、動脈硬化を抑制することを明らかにした。本研究では肥満や糖尿病の病態におけるvaspinの腎臓への作用と機序について検討した。Vaspinトランスジェニック(Tg)およびノックアウト(Vaspin-/-)、野生型マウスを用いて、ストレプトゾトシンで糖尿病を誘発、また高脂肪高蔗糖食で肥満糖尿病モデルを作成し、腎病変について検討した。いずれのモデルにおいても、vapsinは尿細管細胞障害を抑制することが示唆された。

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  • 一次繊毛機能を介したACAM/CLMPの脂肪細胞分化と肥満症における意義

    研究課題/領域番号:26461362  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    村上 和敏, 和田 淳, 江口 潤, 中司 敦子

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    脂肪細胞は余剰エネルギーにより肥大化すると、アディポカイン分泌異常などにより代謝調節機能が障害されメタボリックシンドロームや糖尿病を発症する。我々は、肥満ラットの内臓脂肪組織からホモフィリックな細胞接着に関わる細胞接着分子ACAMを発見した。脂肪細胞でACAMを過剰発現したマウスを高脂肪高蔗糖食で飼育すると、肥満、糖尿病の発症が予防された。このマウスでは脂肪細胞同士がACAMにより接着し、その接着部位に表層アクチン(F-actin)を形成し、電子顕微鏡で同部位にzonula adherens形成を認めた。ACAMは細胞接着と表層アクチン形成により脂肪細胞肥大化を抑制し、肥満や糖尿病を予防する。

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  • Vaspinとその相互作用分子から展開するメタボリック症候群関連創薬

    研究課題/領域番号:26293218  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    和田 淳, 中司 敦子

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    配分額:16510000円 ( 直接経費:12700000円 、 間接経費:3810000円 )

    Vaspinは内臓脂肪組織から発見したserine protease inhibitor (serpin)ファミリーに属する新規アディポカインであり、メタボリックシンドロームにおけるインスリン抵抗性、脂肪肝、脂質代謝異常、動脈硬化を改善する代償因子であるVaspinの受容体であるGRP78/DNAJC1 (DnaJ homolog, subfamily C, member 1)複合体のうちDNAJC1(DnaJ homolog, subfamily C, member 1)のコンディショナルノックアウトマウスを作出した。DNAJC1はメタボリックシンドロームにおける創薬ターゲットと考えられる。

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  • 脂肪蓄積を制御する膜タンパク質と可溶性分泌型のアディポサイトカインとしての意義

    研究課題/領域番号:25126716  2013年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    和田 淳

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    配分額:7020000円 ( 直接経費:5400000円 、 間接経費:1620000円 )

    我々はメタボリック症候群の病態に深く関与する遺伝子群を同定するために、内臓脂肪蓄積を来し2型糖尿病・高血圧・脂質異常症を発症するOtsuka Long-Evans Tokushima Fatty (OLETF) ラットを用いて内臓脂肪特異的な遺伝子群のスクリーニングを施行し新規アディポサイトカインvaspinを同定しその意義について研究している。その過程で膜蛋白質であるACAM (Adipocyte adhesion molecule)とGpnmb/OA (Osteoactivin)を同定した。脂肪細胞の膜蛋白であるACAMおよびGpnmb/OAが、①遺伝子改変動物(ノックアウト(KO)マウスとトランスジェニック(Tg)マウス)により脂肪蓄積に重要な役割を演じていること、②可溶性分泌型細胞外ドメイン蛋白が動物およびヒト患者の血中に存在し、アディポサイトカインとして作用していることを証明し、③これら膜蛋白の細胞内シグナル分子、あるいは可溶性細胞外蛋白の受容体を同定し創薬へと展開するという3点を本研究の目標とする。AP2プロモータを用いたACAM Tgマウスでは通常食、高脂肪高蔗糖食ともに著明に脂肪重量が抑制され体重が減少することが判明した。さらにGpnmb Tgマウスでは体重・脂肪重量・糖代謝には改善を認めなかったが、脂肪肝が改善した。

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  • 糖尿病性腎症の糖鎖プロファイリングによる新規バイオマーカーの同定

    2012年04月 - 2015年03月

    厚生労働科学研究費補助金  難治性疾患等政策研究事業  難治性疾患等政策研究事業

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:20000000円 ( 直接経費:14000000円 、 間接経費:6000000円 )

    糖尿病や糖尿病合併症の進展において、糖鎖異常が関連しているという報告が多くなされている。1991年,高血糖条件下においてヘキソサミン代謝経路が活性化されUDP-N-acetylglucosamineの生産が増加し、核内および細胞質内の糖タンパク質であるO-GlcNAcレベルを増加させるという報告がされた。その後、動物においてヘキソサミン経路の活性化により、インスリン抵抗性が出現することや,糖尿病腎症発症におけるマトリックス蛋白生合成に関与しているTGF-betaの転写活性が亢進すること 、また糖尿病性腎症でみられる細胞周期の停止によるメサンギウム細胞の肥大化を誘導することもわかった。しかし、糖鎖の特徴として構造が複雑であり糖鎖構造を同定するためには大変な労力が必要であり,多くの症例を検討することは困難であった。今回共同研究機関であるGPバイオサイエンスの開発したレクチンアレイにより、糖と結合する蛋白であるレクチンを用いて被験糖鎖とそれぞれに特異性の異なる45種類のレクチンとの結合性が同時に検出可能となった(Nature Methods 2:851-856, 2005)。更にすべてのレクチンの詳細な特異性の情報を格納したデータベースの確立によりパターン認識による糖鎖構造推定が可能となったため,多くの検体について糖鎖を検討することが可能となった
    。本申請では、平成24年度に糖尿病性腎症の尿のレクチンアレイ解析を第1期から4期にわたって施行することにより腎症の進行に特異的な糖鎖プロファイルを同定する。平成25年度は特異的な糖鎖に対応するレクチンをもちいたアフィニティークロマトグラフィーと質量解析(LC-MS/MS)を施行して、腎症の進行を予測しうるマーカーを同定する。平成26年度の最終年度には3年間ストックした尿検体を用いて、バイオマーカーのELISA測定を行い、腎症の進展を予測するバイオマーカーを同定する。
    慢性腎臓病(CKD)の患者数は、1,330万人に達し我が国の成人の8人に一人はCKDであり国民病といえる。さらに糖尿病性腎症は慢性腎臓病の原因のなかで最大の疾患である。現在、糖尿病性腎症の発症や進展のバイオマーカーとしては尿中アルブミンの測定が用いられているが、診断の特異性や腎症の進展の予測因子として満足いくものではない。生体内の蛋白質は酵素的に糖鎖修飾を受け、その機能に多大なる影響を与えており、その重要性は従来から認識されており、糖尿病や糖尿病合併症の進展においても,糖鎖異常が関連しているという報告が多くなされている。共同研究機関であるGPバイオサイエンスの開発したレクチンアレイにより、糖と結合する蛋白であるレクチンを用いて被験糖鎖とそれぞれに特異性の異なる45種類のレクチンとの結合性が同時に検出可能となった。本申請では、平成24年度に糖尿病性腎症の尿のレクチンアレイ解析を第1期から4期にわたって施行することにより腎症の進行に特異的な糖鎖プロファイルを同定する。平成25年度は特異的な糖鎖に対応するレクチンをもちいたアフィニティークロマトグラフィーと質量解析(LC-MS/MS)を施行して、腎症の進行を予測しうるマーカーを同定する。平成26年度の最終年度には3年間ストックした尿検体を用いて、バイオマーカーのELISA測定を行い、腎症の進展を予測するバイオマーカーを同定する。このようなバイオマーカーの同定によって、1.腎症のハイリスク群への集約的治療、すなわちテーラーメイド医療が可能になり医療費の節減につながる、2.ハイリスク患者を選択することにより、糖尿病性腎症の治療薬の治験や開発がより少ない症例数とより短い期間で可能となる、3.腎症のハイリスク群の治療が腎代替療法の回避のみならず心血管病の予防と死亡率の低下につながる、4.糖尿病による全身的な合併症を糖鎖転移酵素や合成阻害剤によって糖鎖異常を是正する治療が開発されるなどの波及効果が期待できる。

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  • Vaspinのメタボリック症候群における意義と創薬への展開

    研究課題/領域番号:23390241  2011年04月 - 2014年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    和田 淳

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    配分額:19240000円 ( 直接経費:14800000円 、 間接経費:4440000円 )

    Vaspinは肥満ラットの内臓脂肪から発見したアディポサイトカインである。メタボリックシンドロームにおいてインスリン抵抗性を改善し、動脈硬化の進展を抑制する代償因子であるとの結論に至った。Vaspinはヒトの血中にも存在し、体格指数やインスリン抵抗性指数と正の相関を認め、2型糖尿病でも血中濃度が増加している。アディポネクチンやレプチンとは異なった血中濃度動態を示しておりメタボリック症候群治療の新たな分子ターゲットである。

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  • 脂肪蓄積を制御する膜蛋白同定とその可溶性分泌型のアディポサイトカインとしての意義

    研究課題/領域番号:23126516  2011年04月 - 2013年03月

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    和田 淳

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    配分額:7020000円 ( 直接経費:5400000円 、 間接経費:1620000円 )

    【背景】我々はメタボリック症候群の病態に深く関与する遺伝子群を同定するために、内臓脂肪蓄積を来し2型糖尿病・高血圧・脂質異常症を発症するOtsuka Long-Evans Tokushima Fatty (OLETF) ラットを用いて内臓脂肪特異的な遺伝子群のスクリーニングを施行し新規アディポサイトカインvaspinを同定しその意義について研究している。その過程で膜蛋白質であるACAM (Adipocyte adhesion molecule)とGpnmb/OA (Osteoactivin)を同定した。
    【目的】Gpnmbは膜蛋白でその可溶性分泌型が報告されているが肥満での役割は不明である。
    【方法】GpnmbのR150X変異を有するDBA/2JマウスからGpnmb欠損(KO)マウスを作成し、さらにaP2プロモーターを用いてTgマウスを作製した。またGpnmbのELISAを用いて血中濃度の検討を行った。
    【結果】高脂肪食飼育KOマウス、Tgマウスでは野生型と比較して体重・内臓脂肪重量に有意差はなかったが、Tgマウスで肝への脂肪沈着、線維化が著明に抑制された。またELISAにより血中の可溶性分泌型の存在を示され、野生型マウスでは肥満によって血中濃度が上昇し、Tgマウスではさらに血中濃度が上昇していた。
    【結論】Gpnmb過剰発現による脂肪肝改善の分子機構として可溶性分泌型の肝組織への抗炎症効果や抗酸化作用が示唆された。

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  • メタボリック症候群と非アルコール性脂肪肝炎の発症機構

    研究課題/領域番号:23659470  2011年 - 2012年

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    和田 淳

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    配分額:3640000円 ( 直接経費:2800000円 、 間接経費:840000円 )

    Phosphatidylethanolamine N-methyltransferase (Pemt)の発現が肥満マウス肝臓で上昇することを見出した。Pemtノックアウトマウスに高脂肪高蔗糖食を負荷したところ肥満と脂肪組織の増大が著明に改善し、インスリン抵抗性が改善され血糖が低下するが、脂肪肝炎を来たし肝硬変や腺腫を発症することが判明した。Pemt活性の低下は非アルコール性脂肪肝炎の発症に深く関与していることを明らかにした

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  • 糖尿病性腎症治療ターゲットとしての核内受容体の研究

    研究課題/領域番号:21249053  2009年 - 2012年

    日本学術振興会  科学研究費助成事業 基盤研究(A)  基盤研究(A)

    槇野 博史, 和田 淳, 小川 大輔

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    配分額:45500000円 ( 直接経費:35000000円 、 間接経費:10500000円 )

    糖尿病性腎症の病態の初期には細胞肥大が重要であり、その後慢性炎症が糖尿病性腎症の進展を促進させている。核内受容体のmodulatorはこれらの病態を総合的に改善する薬剤の候補である。Peroxisome proliferator-activated receptor (PPAR)-δアゴニストおよびLiver X receptor (LXR)アゴニストは抗炎症作用によって治療効果を発揮し、Retinoid X receptor (RXR)アンタゴニストは主として細胞周期の異常を是正して細胞肥大を抑制することが判明した。核内受容体のmodulatorは糖尿病性腎症に有効であると考えられる。

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  • Vaspinのメタボリック症候群における意義

    研究課題/領域番号:20390257  2008年 - 2010年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    和田 淳, 槇野 博史

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    配分額:18590000円 ( 直接経費:14300000円 、 間接経費:4290000円 )

    Vaspinは肥満ラットの内臓脂肪から発見したアディポサイトカインである。肥満マウスへのリコンビナント蛋白の投与実験・トランスジェニックマウスやノックアウトマウスの実験からメタボリック症候群においてインスリン抵抗性を改善する代償因子であるとの結論に至った。Vaspinはヒトの血中にも存在し、体格指数やインスリン抵抗性指数と正の相関を認め、2型糖尿病でも血中濃度が増加している。アディポネクチンやレプチンとは異なった血中濃度動態を示しておりメタボリック症候群治療の新たな分子ターゲットである。

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  • 日本の臨床研究推進に関する調査研究

    研究課題/領域番号:19900005  2007年 - 2008年

    日本学術振興会  科学研究費助成事業 特別研究促進費  特別研究促進費

    山田 信博, 小田 竜也, 和田 淳, 池内 健, 荒井 秀典, 鈴川 和巳, 松原 久裕, 河合 弘二, 柏 淳, 大家 基嗣

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    配分額:9000000円 ( 直接経費:9000000円 )

    イノベーション25で策定している様に、日本は20年後のバイオ立国を目指している。その日本において、日本の高い基礎研究成果がなかなか臨床応用につながらず、結果的には外国で臨床開発された新規医薬品を大量に輸入、消費しているのが現状である。この高額医薬品の費用が外国に流失していく事は経済的に見ても非常に危機的な事態でといえる。日本の基礎生物医学研究の資源をTRを経て臨床医療に還元する仕組みの構築は、緊急の課題として推進されるべきである。しかし、"臨床研究が進んでいる欧米"で構築されたシステムを模倣しても、文化、歴史、哲学、制度が全く異なる日本の臨床研究を推進する事にはならない。日本には、臨床研究家も基礎研究に非常に明るいという世界でも例を見ない優れた特徴があり、この事を十分に考慮した上で一部の臨床医学の人的、経済的資源を臨床研究の推進に充てる必要があると考える。また、省庁の縦割り行政が臨床現場での研究推進を妨げている大きな要因と考えられ、この事に対する制度的な対応も重要なポイントであると考える。

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  • 糖尿病性腎症の成因解明と新しい治療法の開発を目指した探索的研究

    研究課題/領域番号:19590952  2007年 - 2008年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    四方 賢一, 槙野 博史, 和田 淳

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    我々はこれまでの一連の研究によって、糖尿病性腎症の成因には、軽微な慢性炎症(microinflammation)が関与しており、種々のケモカインや炎症性サイトカインとともに、cholecystokinin (CCK)が、腎症の病因に関連している可能性があることを報告した。本研究では、糖尿病性腎症の進展におけるCCKの役割を明らかにするために、CCK type A receptorとtype B receptorの単独ノックアウトマウスと両者のダブルノックアウトマウス(CCK-AB KOマウス)およびwild typeマウスに糖尿病を発症させることにより、CCKが糖尿病性腎症の進展に対して保護的に働く因子であることを明らかにした。さらに、CCK peptideが培養マクロファージからの炎症性サイトカイン産生を抑制すること、糖尿病ラットの腎障害の進行を抑制することを示し、この結果よりCCKが糖尿病性腎症の予防・治療に応用できる可能性があることが示唆された。

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  • ミトコンドリア機能制御による糖尿病合併症の治療戦略

    研究課題/領域番号:18390249  2006年 - 2008年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    槙野 博史, 和田 淳, 四方 賢一

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    配分額:17180000円 ( 直接経費:15800000円 、 間接経費:1380000円 )

    生活習慣の変化により糖尿病患者は増加の一途をたどり、糖尿病性腎症により透析導入となる患者も年々増加している.糖尿病マウスへのtranslocase of inner mitochondrial membrane 44 (Tim44)遺伝子導入によって、糸球体肥大・メサンギウム基質の増加・アルブミン尿の増加が抑制された.Tim44はミトコンドリアへのsuperoxide dismutaseやglutathione dismutaseといった抗酸化酵素をimportしてミトコンドリア由来の活性酸素の産生を抑制することにより治療効果を発揮すると考えられた.

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  • 新規ACE2ホモローグcollectrinの相互作用分子同定と高血圧症への関与

    研究課題/領域番号:17590829  2005年 - 2007年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    和田 淳, 槇野 博史, 四方 賢一

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    配分額:3710000円 ( 直接経費:3500000円 、 間接経費:210000円 )

    進行性腎障害共通の分子メカニズムを明らかにするために、5/6腎臓摘出ICRマウスの腎肥大期において発現の上昇する遺伝子のスクリーニングを行った(Kidney Int 56(2),549-558,1999)。得られた遺伝子のうちNX-17は様々な臓器のノーザン解析から、腎臓特異的に発現することが明らかとなった。この遺伝子の全長のcoding sequenceをマウス、ヒト、ラットにおいてクローニングしたところ、まったく新規の遺伝子であることが判明した。その遺伝子産物は222アミノ酸残基からなり、N末端にシグナルペプチドと膜ドメインを有する膜蛋白である。In situ hybridizationやポリクローナル抗体による免疫染色の結果、腎皮質部及び髄質部の集合管特異的に発現することが判明した。そこで我々はこの新規膜蛋白をcollectrinと命名した(J Biol Chem 276(20),17132-17139,2001)。腎臓においてもHNF-1βが強く発現しているが、collcetrinの発現がHNF-1βによって制御されていることを示した。さらに集合管細胞においてもSNARE複合体形成に関与しており、膜たんぱく質の細胞膜上への表出に関与していることを示した。またcollectrinは集合管細胞のprimary ciliaに発現しており、collectrinの発現をsiRNAによってノックダウンすると、集合管細胞の細胞の極性と分化の維持が失われることを示した(PLoS ONE 5,e414,2007)。さらに高血圧ラットにおいては高塩負荷によるcollectrinの発現上昇が抑制されており、細胞膜上のイオントランスポータや水チャネルなどの発現の制御機構が破たんし、血圧上昇の原因となっていることを見出した。

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  • 糖尿病性腎症の治療における新規ターゲット分子の探索

    研究課題/領域番号:17590828  2005年 - 2006年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    四方 賢一, 槇野 博史, 和田 淳

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    配分額:3500000円 ( 直接経費:3500000円 )

    糖尿病性腎症は、わが国における慢性血液透析導入の最大の原因疾患であり、腎症の成因を解明して新しい治療手段を開発することが重要な課題となっている。我々はこれまでの研究によって、osteopontin, scavengerreceptorA, RANTESやIP-10などのケモカイン・サイトカインやcholecystokinin(CCK)などの炎症関連分子が、腎症の病因に関連している可能性があることを明らかにした。さらに、CCKは腎臓の尿細管上皮細胞に、CCK type A receptor, type B receptorは尿細管とマクロファージに発現していることが明らかになった。そこで、糖尿病性腎症の進展におけるCCKの役割を明らかにするために、CCK type A receptorとtype B receptorの単独ノックアウトマウスと両者のダブルノックアウトマウス(CCK-AB KOマウス)に5/6腎摘出モデルを作成して、腎障害の進展を比較した。その結果、CCK-AB KOマウスでは、他の系統のマウスに比較して、5/6腎摘出後の糸球体硬化の進展が著明に加速していることが明らかとなった。DNAマイクロアレイでは、CCK-AB KOマウスではwild typeに比較して、腎臓における炎症性遺伝子群の発現が亢進していることが明らかとなった。これらの結果から、CCKは糖尿病性腎症の進展に対して保護的に働く因子であることが示唆される。PMAで活性化した培養マクロファージ(THP-1)の培養上清中にCCKペプチドを添加すると、TNF-αなどの炎症性サイトカインのmRNA発現が抑制された。従って、CCKは抗炎症作用を介して腎保護的に作用することが明らかとなり、臨床応用への可能性が示された。

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  • 糖尿病性腎症の発症機構におけるマクロファージの役割の解明と治療への応用

    研究課題/領域番号:15590850  2003年 - 2004年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    四方 賢一, 槇野 博史, 和田 淳

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    配分額:3500000円 ( 直接経費:3500000円 )

    我々は、糖尿病性腎症の成因に炎症メカニズムが関与するとする仮説を検証するために、科学研究費補助金を受けて、10年以上にわたって研究を進めてきた。その結果、糖尿病性腎症患者の腎組織にICAM-1をはじめとする細胞接着分子の発現の亢進とマクロファージの浸潤が見られること、糖尿病発症後きわめて早期にICAM-1の発現が起こり、ICAM-1がマクロファージの浸潤を誘導していることを明らかにした。さらに、ICAM-1ノックアウト(KO)マウスでは対照のwild typeマウスに比べて糖尿病発症後の腎組織におけるマクロファージの浸潤が極めて少なく、腎障害が有意に抑制されることが明らかになった。また、糸球体硬化が進行した時期のモデルである5/6腎摘出モデルにおいても、ICAM-1KOマウスではwild typeマウスに比較して糸球体硬化の進行が抑制されるという結果が得られた。
    次に、糖尿病性腎症の成因に関わる炎症関連分子を解明するとともに、新しい治療ターゲット分子を探索するために、ICAM-1KOマウスとwild typeマウスにストレプトゾトシン誘発糖尿病モデルと5/6腎摘出モデルを作成して、DNAマイクロアレイを用いて腎組織における遺伝子発現プロファイルを経時的に比較した。その結果、osteopontinをはじめとする糖尿病性腎症の成因に関与すると考えられる炎症関連分子を同定することに成功した。

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  • 糖尿病性腎症治療戦略における活性酸素制御-新規分子ターゲットの応用-

    研究課題/領域番号:14370319  2002年 - 2004年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    槇野 博史, 和田 淳, 四方 賢一, 中村 好男

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    配分額:9100000円 ( 直接経費:9100000円 )

    現在の腎臓領域における問題の一つは慢性腎不全患者の増加である。年々透析患者数は増加しており、我が国において2000年末には現在約206,134人が透析を受けている。慢性腎不全患者増加の最大の要因は糖尿病性腎症の増加であり、1998年より糖尿病性腎症が透析導入の原疾患の第一位となった。2000年の1年間に慢性透析に導入された31,925人のうち糖尿病性腎症による導入は11,685人で、全体の36.6%を占めている。しかも糖尿病性腎症を原疾患として透析導入となった場合、心・脳血管障害等のマクロアンギオパチーや感染症のため、5年生存率は約50%と予後は不良である。
    この爆発的な糖尿病性腎症による腎不全の抑制のためには、厳密な血糖コントロールが最も重要であるが、合併症の成立機序を明らかにし、それを作用点とした新しい治療方法の開発も重要である。我々は平成11-13年度基盤研究(B)において、ICRマウスにストレプトゾトシンを投与し糖尿病を誘発することによりヒト糖尿病性腎症のびまん性病変類似の病変がもたらされることを見出した。このモデルを用いることにより、糸球体過剰濾過期のもたらされる遺伝子発現の変化を、遺伝子サブトラクション法や、高密度DNAアレイ法を用いることにより広くスクリーニングを行なった(Wada J et al. Kidney Int 59(4), 1363-1373, 2001)。そのなかにはまったく未知の遺伝子が含まれており、我々はこれらの遺伝子の構造を決定すると共にその機能を報告した(Wada J et al. Proc Natl Acad Sci U S A 95, 144-149, 1998; Yang Q et al. Proc Natl Acad Sci U S A 97(18):9896-9901, 2000)。我々の同定した遺伝子のひとつは、translocase of inner mitochondrial membrane 44(Tim44)である。Tim44はミトコンドリア蛋白を細胞質よりミトコンドリア内へimportするmachinery proteinであり、多くのミトコンドリア蛋白がTim44に依存している。Tim44が上昇するとミトコンドリア蛋白、特にミトコンドリアマトリックス蛋白がimportされるためミトコンドリア機能は亢進すると考えられ、ミトコンドリアの機能亢進とそれにつづく活性酸素の産生がミトコンドリアの機能を逆に障害し、腎症の進展に関与していると推測される。Tim44、uncoupling protein-1(UCP-1)、mitochondrial manganese superoxide dismutase(Mn-SOD)の発現ベクター(pcDNA3.1)を作製した。またそれらを腎尿細管に発現させるために、HVJ-Eベクターを用い基礎的導入実験を行い、発現ベクターの導入が可能となった。Tim44の導入によって活性酸素の低下と糖尿病性腎症の改善を認めた。

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  • 新規ACE2ホモローグcollectrinの発見と腎発生・進行性腎障害への関与

    研究課題/領域番号:14571025  2002年 - 2004年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    和田 淳, 槇野 博史, 四方 賢一

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    配分額:2800000円 ( 直接経費:2800000円 )

    我々は、進行性腎障害に共通の分子メカニズムを明らかにするために、5/6腎臓摘出ICRマウスの腎肥大期において発現の上昇する遺伝子のスクリーニングを行ってきた(Zhang H et al. Kidney Int 56(2),549-558,1999)。すなわち糸球体硬化や、腎間質の線維化を来たす前段階の遺伝子変化がその後の腎硬化の成立に重要であると考えたからである。よってこれらの遺伝子群の同定は進行性腎障害の新しい分子メカニズムが明らかになるばかりではなく、新しい治療ターゲットの同定につながると考えられる。
    そういった遺伝子群のなかの一つであるNX-17は様々な臓器のノーザン解析から、腎臓特異的に発現することが明らかとなった。さらにこの遺伝子の全長のcoding sequenceをマウス、ヒト、ラットにおいてクローニングしたところ、まったく新規の遺伝子であることが判明した。その遺伝子産物は222アミノ酸残基からなり、N末端にシグナルペプチドをと膜ドメインを有するため膜蛋白であると考えられた。In situ hybridizationやポリクローナル抗体による免疫染色の結果、腎皮質部及び髄質部の集合管特異的に発現することが判明した。そのホモロジーサーチより最近その存在が明らかとなったangiotensin converting enzyme 2(ACE2)と47.8%の相同性があることも判明した。そこで我々はこの新規膜蛋白をcollectrinと命名し報告するに至っている(Zhang H et al. J Biol Chem 276(20),17132-17139,2001)。
    Collecrinの構造はまったく新規であるため、その機能の推測は困難であった。しかしヒトcollectrin遺伝子の転写領域を検討した結果Hepatocyte nuclear factor-1α(HNF-1α)の結合配列があることが明らかとなった。腎臓においてはHNF-1βが強く発現しているが、ヒトのHNF-1βの遺伝子異常は糖尿病を来たすことが知られており、MODY5(maturity onset diabetes of the young)と呼ばれている。HNF-1βは主に腎臓に発現しており、そのほか肝臓、膵臓、腸管にもわずかに存在する。Collectrinの発現調節特にHNF-1βとの関連を検討するために、M-1、mIMCD-3細胞のほか複数の集合管細胞細胞株を入手し、CollectrinとHNF-1βの発現を検討した。またCollectrinとの相互作用をもつ蛋白群の同定のために、Yeast two hybrid systemを開始し、5/6腎摘マウス腎臓からmRNAを抽出し、ライブラリーを作製し、スクリーニングを終了した。その結果collectrinはsnapinと相互作用があり、SNARE複合体の形成に関与していることが明らかとなった。

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  • 慢性関節リウマチ滑膜線維芽細胞におけるCXCR3アゴニスト産生誘導分子機構の解明

    研究課題/領域番号:14570413  2002年 - 2003年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    山村 昌弘, 前島 洋平, 和田 淳

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    配分額:3500000円 ( 直接経費:3500000円 )

    関節リウマチ(RA)関節液中にはTh1細胞選択的なケモカイン受容体CXCR3のリガンドであるCXCL9(Mig)、CXCL10(IP-10)、CXCL11(I-TAC)が、変形性関節症(OA)に比較して高濃度に検出された。RA滑膜細胞はCXCR3リガンドをOA滑膜細胞に比較して多量に産生した。RA滑膜のCXCR3発現細胞は主にリンパ濾胞部のCD3+T細胞で、CXCR3リガンドはRA滑膜のマクロファージやリンパ球以外の表層下細胞で発現を認めた。RA滑膜線維芽細胞は、IFN-γ、TNF-α、IL-1などの刺激によりCXCL9/10/11 mRNAが誘導された。滑膜線維芽細胞の培養実験では、CXCL9はIFN-γにより、CXCL10はIFN-γおよびTNF-α/IL-1により強く誘導されたが、IFN-γとTNF-α/IL-1/IL-17の刺激により相乗的に産生が増強された。CXCL11の産生はIFN-γとTNF-α/IL-1により誘導されたが、その産生はCXCL9/10と比較すると弱かった。RA滑膜線維芽細胞は、マクロファージとともに滑膜局所における主要な産生細胞であることが明らかにした。IL-15により活性化されたRA末梢血T細胞は、CXCR3およびCCR5発現が増強された。RA関節液および活性化RA線維芽細胞の培養上清は、IL-15活性化T細胞の遊走反応を誘導し、これらの反応は各CXCR3に対する中和抗体で部分的に阻害された。したがって、CXCR3リガンドがTh1優位のRA滑膜へのT細胞浸潤に関与することが示された。滑膜線維芽細胞において、IFN-γ刺激によりキナーゼ蛋白Jak1のリン酸化と転写因子STAT1の活性化が誘導され、TNF-α刺激によりIKKカスケードリン酸化と転写因子NF-κB活性化が誘導されることを明らかにした。TNF-αおよびIL-1によるCXCR3リガンド産生誘導には,JNKおよびp38キナーゼのMAKキナーゼカスケードの活性化が関与することを明らかにした。CXCL9-11の各5'上流非翻訳プロモーター領域を挿入したルシフェラーゼ遺伝子ベクターを滑膜線維芽細胞株に導入し、転写レベルでのIFN-γとTNF-αの相乗作用を明らかにした。

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  • 糖尿病性腎症の発症機構にマクロファージが果たす役割の解明―ICAM-1 KO mouseとMacrophage scavenger receptor KO mouseを用いた研究―

    研究課題/領域番号:13671116  2001年 - 2002年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    四方 賢一, 和田 淳, 槇野 博史, 松田 充浩

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    配分額:3500000円 ( 直接経費:3500000円 )

    糖尿病性腎症はわが国における末期腎不全の原因疾患の第一位を占め、現在も増加を続けている。糖尿病性腎症の発症機構を明らかにして新しい治療法を開発することは、糖尿病患者の生命予後を改善し、末期腎不全患者の増加を阻止するための重要な課題である。
    糖尿病性腎症患者の腎組織には糸球体と間質にマクロファージの浸潤が認められることから、腎症の成因にマクロファージを中心とした炎症メカニズムが関与することが示唆される。我々は、これまでに、糖尿病性腎症におけるマクロファージの浸潤はICAM-1によって誘導されていることを明らかにした。本研究では、糖尿病性腎症の成因におけるマクロファージの役割を解明する目的で、ICAM-1ノックアウトマウス(ICAM-1 KOマウス)とmacrophage scavenger receptor-Aノックアウトマウス(SR-A KOマウス)を用いた。両マウスとwild typeマウスにstreptozotocinを投与して糖尿病を惹起し、6ヶ月間観察し腎組織を採取した。ICAM-1 KOマウスでは、wild typeマウスに比べて、糖尿病発症後の腎臓へのマクロファージの浸潤が抑制されるとともに、アルブミン尿、糸球体でのTGF-βの発現、メサンギウム基質の増加と間質の線維化が抑制された。この結果から、糖尿病性腎症の成因にマクロファージが重要な役割を果たすことが証明された。
    一方、SR-A KOマウスにおいてもICAM-1 KOマウスの場合と同様に、腎組織へのマクロファージの浸潤が減少するとともに腎障害の進展が抑制された。このことから、SR-Aは糖尿病状態における腎組織へのマクロファージの浸潤に関与していることが明らかとなった。
    さらに両実験系において、DNAマイクロアレイを用いて腎組織における遺伝子発現プロファイルを比較した。その結果、wild typeマウスの腎臓で、糖尿病発症後に増加する炎症関連遺伝子群を同定した。次に、これらの炎症関連遺伝子群の中で、ICAM-1 KOマウスではwild typeマウスと比較して発現が抑制される遺伝子群を同定した。これらの分子は、糖尿病性腎症の発症と進展に関与している可能性がある。

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  • 慢性関節リウマチにおけるTh1型免疫反応の成立機構の解明

    研究課題/領域番号:12670426  2000年 - 2001年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    山村 昌弘, 和田 淳

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    配分額:3200000円 ( 直接経費:3200000円 )

    インターロイキン-12(IL-12)は,関節リウマチ(RA)の滑膜T細胞のインターフェロン-γ(IFN-γ)産生を選択的かつ強力に誘導した。一方,IL-18には直接的なIFN-γ誘導活性を認めなかったが,IL-12で誘導されるIFN-γ産生はIL-18により増強し,抗IL-18抗体により著明に低下した。したがって,RA滑膜に多量に存在するIL-18のTh1型免疫反応における役割は,発現の乏しいIL-12のIFN-γ誘導活性を増強することにあるものと推定された。
    RA末梢血CD4+T細胞に有意なIL-12受容体(IL-12R)β1/β2鎖の発現を認めなかったが,抗CD3抗体刺激により誘導されるIL-12R発現は健常人CD4+T細胞より強かった。また,RA滑膜に浸潤したCD4+T細胞の一部にIL-12Rβ1/β2鎖発現がみられ,IL-12Rβ2鎖の転写活性を認めた。滑膜CD4+T細胞のIL-12R発現は,抗CD3抗体とIL-18の刺激により増強された。一方,RA末梢血CD4+T細胞にはIL-18Rα/β鎖の構成的な発現を認め,その発現は健常人より強く,滑膜CD4+T細胞ではさらに発現が増強していた。IL-12Rβ1/β2鎖は主にIL-18Rα鎖発現細胞に誘導され,RA滑膜CD4+T細胞の大部分はIL-18Rα鎖発現能をもつIFN-γ産生細胞であることを明らかにした。また,IL-12,IL-18で活性化されたT細胞では,それぞれ転写因子STAT4,NF-κBの活性化が誘導された。したがって,選択的浸潤あるいは発現増強によりRA滑膜に集積したIL-18R+CD4+T細胞は,CD3およびIL-18を介した刺激により機能的IL-12Rが一部細胞に誘導され,IL-12およびIL-18に対する反応性を獲得したIFN-γ産生Th1細胞として機能することが示唆された。
    さらに,RA滑膜T細胞におけるTh1選択的CXCR3ケモカイン受容体の発現を明らかにし,また,CD4+T細胞はTh2関連抗原とされるCD30分子の発現能が低下しており,RA関節内ではCD30+CD4+T細胞はアポトーシスにより除去される可能性を示した。

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  • 糖尿病性腎症における糸球体過剰濾過の分子生物学的解明

    研究課題/領域番号:11470218  1999年 - 2001年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    槇野 博史, 肥田 和之, 四方 賢一, 和田 淳

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    配分額:16500000円 ( 直接経費:16500000円 )

    糖尿病性腎症では腎症早期に起こる糸球体過剰濾過がその後の病態の発症と進展に深く関与していると言われている。特に1型糖尿病では、糸球体過剰濾過の時期が存在することは臨床的にも明らかである。その病態の成立には、高血糖、糸球体血行動態の異常、プロスタグランジン、一酸化窒素などの関与が指摘されているが、その分子生物学的機序は不明である。そこで糸球体過剰濾過が存在する糖尿病早期腎症の腎臓でどのような遺伝子の変化がもたらされるかを検討することとした。まず多くの遺伝子の変化を捉えるために、high density DNA array (GenomeSystem社製Gene Discovery Array ; GDA)を採用した。GDAフィルター上には、整理され重複をさけた約2万EST(expressed sequence tag)cloneがスポットされている。これら遺伝子群のうちシグナルの差が5倍以上あるクローンを選択したところ、16個が糖尿病腎で発現が上昇し、65個でその発現が低下していた。37個の既知遺伝子群のうち24は、糖・脂質・アミノ酸代謝関連遺伝子(n=5)、トランスポーター(n=6)、シグナル伝達物質(n=4)、転写調節因子(n=7)、細胞外基質関連遺伝子(n=2)に分類された。また興味深いことに12のシグナル伝達物質、転写調節因子は腎やその他の臓器で臓器発生や、分化に関連した遺伝子であり、糖尿病性腎症において、腎細胞の分化状態の変化がその後の形質変化の初期段階であることが示唆された。

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  • 腎疾患に対する抗接着分子療法の臨床応用に関する基礎的検討-硫酸化オリゴ糖の抗セレクチン剤としての有用性-

    研究課題/領域番号:11671036  1999年 - 2000年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    四方 賢一, 肥田 和之, 和田 淳, 杉本 光, 土山 芳徳

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    配分額:3900000円 ( 直接経費:3900000円 )

    本研究では、糸球体腎炎の新しい治療法として抗接着分子療法を開発することを目的して、セレクチン阻害薬の腎炎抑制効果を基礎的に検討した。最初に、セレクチン阻害薬として硫酸化ヒアルロン酸(SHA)を用いた。モデルとしてWKYラットに抗糸球体基底膜抗体を投与して作成される半月体形成性糸球体腎炎モデルとThy.1抗体を投与することによるメサンギウム増殖性糸球体腎炎モデルを用いた。まず、抗P-セレクチン抗体と抗L-セレクチン抗体を用いた阻害実験を行い、腎組織へのマクロファージの浸潤にP-セレクチンが関与していることを明らかにするとともに、in vitroにおける検討により、SHAがセレクチン阻害活性をもつことを確認した。次に、両モデルにSHAを投与して腎炎抑制効果を検討した。両モデルにおいて、SHAの投与により蛋白尿減少効果と組織学的に半月体形成の減少が認められた。さらに、SHAと同じく硫酸化オリゴ糖の一種である硫酸化コロミン酸(SCA)の半月体形成性糸球体腎炎ラットに投与したところ、SHAよりもさらに強い腎炎抑制効果が確認された。これらの結果から、セレクチン阻害活性をもつ硫酸化オリゴ糖は、糸球体腎炎の治療薬として臨床応用できる可能性があると考えられる。また、マクロファージから産生される組織傷害因子であるNOを阻害する化合物である選択的iNOS阻害薬が、半月体形成性糸球体腎炎に対して治療効果を示すことが明らかとなり、硫酸化オリゴ糖とともに新しい腎炎治療薬として有望な薬剤であると考えられた。

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  • 新しく発見された動物レクチンGalectin-9の研究

    研究課題/領域番号:10770199  1998年 - 1999年

    日本学術振興会  科学研究費助成事業 奨励研究(A)  奨励研究(A)

    和田 淳

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    配分額:2200000円 ( 直接経費:2200000円 )

    Galectin-9は胸腺細胞の細胞膜上の糖鎖に結合しアポトーシスを誘導することが知られている。またgalectin-1も活性化T細胞や胸腺細胞に対して同様の効果が報告されている。よってGalectinはT細胞が関与する自己免疫疾患に対して免疫抑制剤のとなりうる可能性がある。ウサギ抗糸球体基底膜抗体をWKYラットに投与し半月体形成性腎炎を惹起しGalectinによる腎炎抑制効果を検討した。このモデルではウサギ抗体が糸球体基底膜に結合した後、ウサギIgGに対する抗体が産生され、さらに基底膜に結合することにより組織障害が進展する。また糸球体にCD8^+細胞の浸潤を来たし、その後のマクロファージ浸潤を促すことによりさらなる組織障害をもたらすと考えられている。デキサメサゾンの投与は、抗ウサギIgG抗体の産生を完全に抑制し、糸球体内への細胞浸潤も完全に抑制することにより、組織障害、蛋白尿を改善した。Galectin-9の投与では抗ウサギIgG抗体の産生は抑制されないものの、糸球体内へのCD8^+細胞の浸潤を抑制し、その後のマクロファージの浸潤を抑制し、改善効果を認めた。一方Galectin-1やGalectin-3の投与では抗体産生、CD8^+細胞の糸球体への浸潤を抑制しないもののマクロファージの浸潤を抑制した。ラット脾から採取したリンパ球でアポトーシスを検討したところ、デキサメサゾンはCD4^+、CD8^+細胞ともにアポトーシスを誘導したが、Galectin-9は活性化CD8^+細胞に対して特異的にアポトーシスを誘導した。Galectin-1やGalectin-3はin vivoではアポトーシスを誘導しなかった。以上よりGalectin-9の半月体形成性腎炎に対する治療効果は主としてCD8^+細胞にアポトーシスを誘導することにより発揮され、より副作用の少ない免疫抑制剤開発の端緒となる。

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  • 腎・免疫・内分泌代謝内科学II(演習・実習) (2022年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(講義・演習) (2022年度) 特別  - その他

  • 臨床医歯科学概論 (2022年度) 集中  - その他

  • 選択制臨床実習(腎・免疫・内分泌代謝内科学) (2022年度) 特別  - その他

  • 選択制臨床実習(腎・免疫・内分泌代謝内科学)2 (2022年度) 特別  - その他

  • メタボリックシンドローム特論 (2021年度) 特別  - その他

  • 免疫系(臓器・系別統合講義) (2021年度) 特別  - その他

  • 内分泌・代謝系(臓器・系別統合講義) (2021年度) 特別  - その他

  • 病態機構学演習 (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学(基本臨床実習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(演習・実習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(演習・実習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(演習・実習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(講義・演習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(講義・演習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(演習・実習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(講義・演習) (2021年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(講義・演習) (2021年度) 特別  - その他

  • 臨床医歯科学概論 (2021年度) 集中  - その他

  • 選択制臨床実習(腎・免疫・内分泌代謝内科学) (2021年度) 特別  - その他

  • 選択制臨床実習(腎・免疫・内分泌代謝内科学)2 (2021年度) 特別  - その他

  • メタボリックシンドローム特論 (2020年度) 特別  - その他

  • 免疫系(臓器・系別統合講義) (2020年度) 特別  - その他

  • 内分泌・代謝系(臓器・系別統合講義) (2020年度) 特別  - その他

  • 病態機構学演習 (2020年度) 通年  - その他

  • 病態機構学総論 (2020年度) 通年  - その他

  • 腎・免疫・内分泌代謝内科学(基本臨床実習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(演習・実習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(演習・実習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(講義・演習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学I(講義・演習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(演習・実習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(演習・実習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(講義・演習) (2020年度) 特別  - その他

  • 腎・免疫・内分泌代謝内科学II(講義・演習) (2020年度) 特別  - その他

  • 臨床医歯科学概論 (2020年度) 集中  - その他

  • 選択制臨床実習(腎・免疫・内分泌代謝内科学) (2020年度) 特別  - その他

  • 選択制臨床実習(腎・免疫・内分泌代謝内科学)2 (2020年度) 特別  - その他

▼全件表示

 

メディア報道

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    日本経済新聞  2016年5月9日

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    NHK岡山放送局  2016年5月6日

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    山陽新聞社  2015年12月7日

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  • 腎臓タンパク質・コレクトリン 高血圧発症に関与か

    山陽新聞社・共同通信社  2008年11月19日

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  • 新タンパク質バスピン発見 インスリンの作用高め血糖値低下

    NHK全国ニュース・共同通信社・毎日新聞全国版・New York (Reuters Health)など  2005年7月9日

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