論文 - 古橋　眞人

ゴリムマブが誘因となった薬剤起因性自己免疫疾患でネフローゼ症候群を発症した1例

長谷川 諒, 安部 功記, 松久 優雅, 小林 広学, 田中 希尚, 後町 結, 茂庭 仁人, 古橋 眞人, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 6 ) 700 - 700  2019年08月

ネフローゼ症候群を呈したシェーグレン症候群による二次性膜性腎症に対しステロイドが奏効した1例

増田 拳, 田中 希尚, 茂庭 仁人, 後町 結, 古橋 眞人, 小川 弥生, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  61 ( 6 ) 762 - 762  2019年08月

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines.

Masato Furuhashi, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Yukimura Higashiura, Masayuki Koyama, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Journal of diabetes investigation   10 ( 4 ) 1059 - 1067  2019年07月  [査読有り]  [国内誌]

　概要を見る

AIMS/INTRODUCTION: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catalyzes uric acid formation in the purine metabolism, is involved in an increase in reactive oxygen species. Plasma XOR activity has been shown to be associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance. MATERIALS AND METHODS: The association between plasma XOR activity, measured by using liquid chromatography and mass spectrometry, and levels of adipokines, including adiponectin, fatty acid-binding protein 4 (FABP4) and fibroblast growth factor 21 (FGF21), was investigated in 282 participants (male/female: 126/156) of the Tanno-Sobetsu Study who were not taking medication. RESULTS: Women had lower plasma XOR activity than did men. Smoking habit was associated with increased activity. Plasma XOR activity was positively correlated with concentrations of FABP4 (r = 0.192, P < 0.001) and FGF21 (r = 0.208, P < 0.001), homeostasis model assessment of insulin resistance as an index of insulin resistance and uric acid, and was negatively correlated with adiponectin level (r = -0.243, P = 0.001). Multivariate regression analyses showed that levels of adiponectin, FABP4 and FGF21 were independent determinants of plasma XOR activity after adjusting age, sex, uric acid and homeostasis model assessment of insulin resistance. With additional adjustment of smoking habit, the level of FABP4, but not that of adiponectin or FGF21, remained as an independent predictor of plasma XOR activity. CONCLUSIONS: Plasma XOR activity was independently associated with levels of adipokines in a general population of individuals not taking medication.

DOI PubMed

心肺停止を伴う急性心筋梗塞を契機に診断に至った1型CD36欠損症および家族性高コレステロール血症の合併例

西川 諒, 古橋 眞人, 伊藤 良介, 續 太郎, 小山 雅之, 村中 敦子, 國分 宣明, 堀 美香, 小倉 正恒, 斯波 真理子, 三浦 哲嗣

日本動脈硬化学会総会プログラム・抄録集 ( (一社)日本動脈硬化学会 )  51回   1 - 3  2019年07月

Accuracy of flash glucose monitoring in insulin-treated patients with type 2 diabetes.

Tatsuya Sato, Hiroto Oshima, Kei Nakata, Yukishige Kimura, Toshiyuki Yano, Masato Furuhashi, Masaya Tanno, Takayuki Miki, Tetsuji Miura

Journal of diabetes investigation   10 ( 3 ) 846 - 850  2019年05月  [国内誌]

　概要を見る

The present study evaluated the accuracy of interstitial glucose measurements by flash glucose monitoring (FGM) and continuous glucose monitoring (CGM). Five diabetes patients simultaneously underwent FGM (FreeStyle Libre Pro) and CGM (iPro™2), and their glucose levels were compared with venous blood and capillary blood glucose levels. The range of daily venous blood glucose levels (30 measurements) was 70-245 mg/dL, with a median of 138 mg/dL. There were good correlations of glucose levels measured by FGM (r2  = 0.90, mean absolute relative difference 8.2 ± 5.6%), CGM (r2  = 0.86, mean absolute relative difference 9.2 ± 9.1%) and capillary blood (r2  = 0.87, mean absolute relative difference 7.2 ± 7.2%) with venous blood glucose levels. The accuracy of FGM measurements was also shown against CGM, with 99.9% of the FGM values (1,279 measurements) being within the Parkes error grid zones A and B. The results suggest that the accuracy of FGM is similar to that of CGM, and that FGM is a useful tool for determining daily glucose profile.

DOI PubMed

糖尿病の外来診療における慢性合併症評価実態の検討

伊野 祥哉, 中田 圭, 東浦 幸村, 佐藤 達也, 矢野 俊之, 古橋 眞人, 丹野 雅也, 三木 隆幸, 斎藤 重幸, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  62 ( Suppl.1 ) S - 306  2019年04月

Differential Phenotypes in Perivascular Adipose Tissue Surrounding the Internal Thoracic Artery and Diseased Coronary Artery.

Ryosuke Numaguchi, Masato Furuhashi, Megumi Matsumoto, Hiroshi Sato, Yosuke Yanase, Yosuke Kuroda, Ryo Harada, Toshiro Ito, Yukimura Higashiura, Masayuki Koyama, Marenao Tanaka, Norihito Moniwa, Masanori Nakamura, Hirosato Doi, Tetsuji Miura, Nobuyoshi Kawaharada

Journal of the American Heart Association   8 ( 2 ) e011147  2019年01月  [査読有り]  [国際誌]

　概要を見る

Background Perivascular adipose tissue ( PVAT ) is causally associated with vascular function and the pathogenesis of vascular disease in association with metabolically driven chronic inflammation called metaflammation. However, the difference in PVAT surrounding the coronary artery ( CA - PVAT ) and that surrounding the internal thoracic artery (ITA-PVAT), a vessel resistant to atherosclerosis, remains unclear. Herein, we investigated whether CA - PVAT , ITA - PVAT , and subcutaneous adipose tissue ( SCAT ) have distinct phenotypes. Methods and Results Fat pads were sampled from 44 patients (men/women, 36:8; age, 67±13 years) with CA disease who underwent elective CA bypass grafting. Adipocyte size in ITA - PVAT and that in CA - PVAT were significantly smaller than that in SCAT . A greater extent of fibrosis and increased gene expression levels of fibrosis-related molecules were observed in CA - PVAT than those in SCAT and those in ITA - PVAT . CA - PVAT exhibited more pronounced metaflammation, as indicated by a significantly larger extent of CD 68-positive and CD 11c-positive M1 macrophages, a lower ratio of CD 206-positive M2 to CD 11c-positive M1 macrophages, a lower gene expression level of adiponectin, and higher gene expression levels of inflammatory cytokines and inflammasome- and endoplasmic reticulum stress-related molecules, than did ITA - PVAT and SCAT . Expression patterns of adipocyte developmental and pattern-forming genes were totally different among SCAT , ITA - PVAT, and CA - PVAT . Conclusions The phenotype of ITA - PVAT is closer to that of SCAT than that of CA - PVAT , which may result from inherent differences in adipocytes. ITA - PVAT appears to be protected from metaflammation and consecutive adipose tissue remodeling, which may contribute to the decreased atherosclerotic plaque burden in the ITA.

DOI PubMed

Unexpected high plasma xanthine oxidoreductase activity in female subjects with low levels of uric acid.

Masato Furuhashi, Kazuma Mori, Marenao Tanaka, Takuto Maeda, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Masayuki Koyama, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Endocrine journal   65 ( 11 ) 1083 - 1092  2018年11月  [査読有り]  [国内誌]

　概要を見る

Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.

DOI PubMed

【腎と高血圧:最新研究から得られた新たな知見】CKDの新規治療ターゲットとしての異所性FABP4発現の可能性

古橋 眞人, 東浦 幸村, 田中 希尚

血圧 ( (株)先端医学社 )  25 ( 9 ) 630 - 635  2018年09月

　概要を見る

脂肪酸結合蛋白4(FABP4/A-FABP/aP2)は、主に脂肪細胞とマクロファージに存在し、メタボリックシンドロームの成因に深く関わる。FABP4はシグナルペプチドを有さないものの脂肪細胞から脂肪分解とともに分泌されてアディポカインとして作用する。また、血中FABP4濃度は肥満、糖尿病、脂質異常症、高血圧、動脈硬化、心血管死と関連する。現在、尿中FABP1(L-FABP)排泄量が腎尿細管機能障害マーカーとして臨床応用されているが、我々は傷害された糸球体内皮細胞にFABP1ではなくFABP4が異所性に発現することを初めて見出し、糸球体FABP4発現量や尿中FABP4排泄量が尿蛋白量や腎予後に関わることを報告した。CKDのうち特に糸球体傷害疾患に対して、異所性FABP4発現が新規の治療ターゲットとなる可能性が示唆される。(著者抄録)

糖尿病合併IgA腎症に対し扁摘パルス療法を施行した3症例

茂庭 仁人, 後町 結, 田中 希尚, 古橋 眞人, 小川 弥生, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 6 ) 937 - 937  2018年08月

Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population.

Masato Furuhashi, Megumi Matsumoto, Marenao Tanaka, Norihito Moniwa, Takayo Murase, Takashi Nakamura, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Circulation journal : official journal of the Japanese Circulation Society   82 ( 7 ) 1892 - 1899  2018年06月  [査読有り]  [国内誌]

　概要を見る

BACKGROUND: Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR promotes oxidative stress-related tissue injury. We investigated the associations between metabolic parameters and plasma XOR activity measured by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry to detect [13C2,15N2]-uric acid using [13C2,15N2]-xanthine as a substrate.Methods and Results:A total of 627 Japanese subjects (M/F, 292/335) from the Tanno-Sobetsu Study, a population-based cohort, were recruited. Plasma XOR activity was significantly higher in males than in females, and habitual smoking was associated with elevation of activity. Plasma XOR activity was positively correlated with body mass index (BMI; r=0.323, P<0.001), waist circumference, blood pressure, and levels of liver enzymes including alanine transaminase (r=0.694, P<0.001), uric acid (r=0.249, P<0.001), triglycerides (r=0.312, P<0.001), hemoglobin A1c, fasting glucose, insulin and HOMA-R (r=0.238, P<0.001) as a marker of insulin resistance and was negatively correlated with high-density lipoprotein cholesterol level. On stepwise and multivariate regression analyses, BMI, smoking and levels of alanine transaminase, uric acid, triglycerides and HOMA-R were independent predictors of plasma XOR activity after adjustment for age and gender. CONCLUSIONS: Plasma XOR activity is a novel biomarker of metabolic disorders in a general population.

DOI PubMed

良性小脳髄膜腫切除後に寛解に至った膜性腎症の1例

森 和真, 山下 智久, 安部 功記, 木村 幸滋, 田中 希尚, 茂庭 仁人, 古橋 眞人, 小川 弥生, 三浦 哲嗣

日本内科学会雑誌 ( (一社)日本内科学会 )  107 ( 6 ) 1102 - 1106  2018年06月

　概要を見る

症例は69歳女性で、嘔気を伴う頭痛を自覚し、救急搬送された。意識障害に加え、CTで右小脳に石灰化を伴う4cm大の腫瘍とそれに伴う水頭症を認めた。頭部MRI T2強調で、腫瘍は不均一な高信号を示した。第2病日に緊急脳室ドレナージ、頭蓋内腫瘍摘出術を施行し、摘出病理標本から良性線維性髄膜腫と診断された。入院時から尿蛋白(4+)、血清Albは2.5→1.3g/dlまで低下し、第6病日から4日間アルブミン製剤を投与した。腫瘍切除後に蛋白尿は速やかに減少した。全身状態が改善した第28病日に腎生検を施行し、膜性腎症と診断した。さらに、特発性膜性腎症に特異的とされる抗PLA2R抗体染色陽性、IgGサブクラス染色でのIgG4優位を認めた。電子顕微鏡所見で上皮下に高電子密度沈着物(EDD)を認め、一部の電子密度は低下していることから、Ehrenreich Churg分類Stage III〜IVと診断した。第35病日に尿蛋白量は24時間蓄尿検査で0.4g/日まで減少した。髄膜腫の抗PLA2R抗体染色を行うも陰性であった。

腎疾患症例における尿FABP4排泄量の臨床的意義 腎生検例を用いた検討

田中 希尚, 古橋 眞人, 松本 めぐみ, 山下 智久, 茂庭 仁人, 後町 結, 前田 卓人, 滝沢 英毅, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 423 - 423  2018年04月

脂肪酸結合タンパク4(FABP4)濃度は動脈硬化進展度の予測因子である

古橋 眞人, 湯田 聡, 村中 敦子, 川向 美奈, 松本 めぐみ, 田中 希尚, 茂庭 仁人, 大西 浩文, 斎藤 重幸, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  61 ( Suppl.1 ) S - 319  2018年04月

一般住民における尿酸低値例での血漿キサンチン酸化還元酵素(XOR)活性の検討

森 和真, 古橋 眞人, 田中 希尚, 村瀬 貴代, 中村 敬志, 前田 卓人, 大西 浩文, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 365 - 365  2018年04月

急性心不全入院における急性腎障害予測スコア(S-ARS)は1年後の死亡を予測する

柴田 智, 山下 智久, 菅原 浩仁, 田中 希尚, 茂庭 仁人, 古橋 眞人, 三木 隆幸, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  60 ( 3 ) 357 - 357  2018年04月

Flash Glucose Monitoringを用いた血糖値予測妥当性の検討

青山 ちひろ, 三木 隆幸, 大島 洸人, 中田 圭, 佐藤 達也, 矢野 俊之, 古橋 眞人, 齋藤 重幸, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  61 ( Suppl.1 ) S - 191  2018年04月

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication.

Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Megumi Matsumoto, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Circulation journal : official journal of the Japanese Circulation Society   82 ( 4 ) 1121 - 1129  2018年03月  [査読有り]  [国内誌]

　概要を見る

BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.Methods and Results:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.

DOI PubMed

糖尿病や検尿異常のない場合もLDL-コレステロール高値はCKDの危険因子となる

長南 新太, 山下 智久, 松本 環, 大西 浩文, 塙 なぎさ, 田中 希尚, 茂庭 仁人, 古橋 眞人, 三浦 哲嗣

日本内科学会雑誌 ( (一社)日本内科学会 )  107 ( Suppl. ) 252 - 252  2018年02月

A Case of Crescentic Glomerulonephritis Complicated with Hypocomplementemic Urticarial Vasculitis Syndrome and ANCA-Associated Vasculitis

Marenao Tanaka, Norihito Moniwa, Tomohiro Mita, Toshiyuki Tobisawa, Tamaki Matsumoto, Atsushi Mochizuki, Tomohisa Yamashita, Toshiyuki Yano, Masato Furuhashi, Tetsuji Miura

Case Reports in Nephrology and Dialysis ( S. Karger AG )  7 ( 3 ) 144 - 153  2017年11月  [査読有り]

DOI