論文 - 北村 和雄
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レニン・アンジオテンシン・アルドステロン系研究の新展開、プロアンジオテンシン-12研究の最前線 査読あり
加藤丈司、桑迫健二、小松洋一、永田さやか、北村和雄
Angiology Frontier 13 13 ( 1 ) 13 - 18 2014年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Association between renal vasculature changes and generalized atherosclerosis: An autopsy survey 査読あり
Iwakiri T., Sato Y., Matsuura Y., Hatakeyama K., Marutsuka K., Yamashita A., Fujimoto S., Kitamura K., Asada Y.
Journal of Atherosclerosis and Thrombosis 21 ( 2 ) 99 - 107 2014年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Atherosclerosis and Thrombosis
Aim: To examine the association between renal vasculature changes and generalized atherosclerosis using autopsy cases. Methods: We histologically examined 107 autopsy patients (mean age, 68.4 years; 64% men; 81% non-CVD) to investigate the association between renal vasculature changes and generalized atherosclerosis. We measured the intima/media (I/M) ratio for the renal, intrarenal and systemic arteries (coronary, cerebral, common carotid and common iliac), calculated the rates of arteriolar hyalinization and global glomerulosclerosis and evaluated the frequency of advanced lesions (AHA classification ≥IV) in the systemic arteries. Results: The I/M ratios of the renal and intrarenal arteries and the rate of global glomerulosclerosis increased with age, while the rates of arteriolar hyalinization and global glomerulosclerosis were associated with diabetes and hypertension (all p<0.05). The I/M ratio of the coronary artery was independently associated with the rate of global glomerulosclerosis (p<0.05). The frequency of advanced atherosclerotic lesions in the coronary and cerebral arteries was also correlated with the I/M ratio of the renal artery and rates of arteriolar hyalinization and global glomerulosclerosis (all p<0.05). The frequency of advanced lesions in the cerebral and common carotid arteries was independently associated with the I/M ratio of the renal artery and the rate of renal arteriolar hyalinization (odds ratio (OR) with [95% confidence interval]; 5.09 [1.15-27.9] and 4.11 [1.38-13.9], respectively). Conclusions: The results of this study demonstrated that pathological changes in four portions of the renal vasculature differ. Renal vasculature changes except the intrarenal arteries were significantly associated with those observed in the cerebral, common carotid and coronary arteries.
DOI： 10.5551/jat.19869
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Kawagoe J., Ishikawa T., Iwakiri H., Date H., Imamura T., Kitamura K.
International Heart Journal 55 ( 3 ) 239 - 243 2014年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Heart Journal
Adiponectin has antiatherosclerotic properties and is also produced in the local coronary circulation. We previously reported that signifi cantly less adiponectin was produced in the coronary circulation of patients with than without coronary artery disease (CAD). The goal of this study was to determine whether adiponectin production in the coronary circulation could predict future cardiovascular events in patients with CAD. Forty-eight CAD patients whose left anterior descending coronary arteries required percutaneous coronary intervention (PCI) were enrolled. The amount of adiponectin production in the coronary circulation was defi ned as the plasma adiponectin level at the great cardiac vein minus that at the orifi ce of the left coronary artery. All patients were divided by adiponectin production level in the coronary circulation into the adiponectin-positive production group (> 0 μg/ mL) and adiponectin-negative production group (≤ 0 μg/mL). Median follow-up period was 66 months (maximum, 108 months). The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, heart failure, nonfatal myocardial infarction, revascularization with PCI or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. Sixteen MACE occurred. The incidence of MACE was signifi cantly higher in the adiponectin-negative production group than in the adiponectin-positive production group (P = 0.02). In multivariate analysis, adiponectin-negative production was a predictor of MACE (P = 0.03). Kaplan-Meier analysis revealed that the MACE-free rate was signifi cantly lower in the adiponectin-negative production group than in the adiponectin-positive production group. Adiponectin production in the coronary circulation with CAD may be associated with MACE.
DOI： 10.1536/ihj.13-287
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Inhibited cardiac hypertrophy in proadrenomedullin NH2-Terminal 20 peptide-transgenic rat with unilateral ... 査読あり
Yuan-NingCao、北村和雄、桑迫健二、加藤丈司、西平賢作、浅田祐士郎、江藤胤尚
Journal of Adaptation Medicine 9 ( 1 ) 30 - 30 2014年
掲載種別：研究論文（学術雑誌）
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活動性潰瘍性大腸炎の入院治療に伴う合併症に関する検討 査読あり
芦塚伸也、三宮一朗、増田稔、三木吾郎、星子新理、松本英丈、中島孝治、稲津東彦、北村和雄
日本消化器病学会雑誌 111 ( suppl-2 ) 888 - 888 2014年
掲載種別：研究論文（学術雑誌）
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一般住民におけるアドレノメデュリンとナトリウム利尿ペプチドの血中レベルと慢性腎臓病発症 査読あり
加藤丈司、桑迫健二、北村和雄
日本内分泌学会雑誌 90 ( 2 ) 751 - 751 2014年
掲載種別：研究論文（学術雑誌）
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ビッグアンジオテンシン-25 : ヒト尿中の主要なアンジオテンシン関連ペプチド 査読あり
永田さやか、北村和雄
最新医学 69 ( 11月増刊 ) 2276 - 2286 2014年
掲載種別：研究論文（学術雑誌）
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Long-term survival of patients with IgA nephropathy after dialysis therapy. 査読あり
Komatsu H, Kikuchi M, Nakagawa H, Fukuda A, Iwakiri T, Toida T, Sato Y, Kitamura K, Fujimoto S
Kidney Blood Press Res 37 ( 6 ) 649 - 656 2013年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Big angiotensin-25: A novel glycosylated angiotensin-related peptide isolated from human urine. 査読あり
Nagata S, Hatakeyama K, Asami M, Tokashiki M, Hibino H, Nishiuchi Y, Kuwasako K, Kato J, Asada Y, Kitamura K
Biochem Biophys Res Commun 441 ( 4 ) 757 - 762 2013年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Adrenomedullin as a potential therapeutic agent for inflammatory bowel disease 査読あり
Ashizuka S., Inatsu H., Inagaki-Ohara K., Kita T., Kitamura K.
Current Protein and Peptide Science 14 ( 4 ) 246 - 255 2013年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Current Protein and Peptide Science
Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide with potent vasodilating action but is now known to exert a wide range of physiological effects, including cardiovascular protection, neovascularization, and apoptosis suppression. A variety of tissues, including the gastrointestinal tract, have been shown to constitutively produce AM. Pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1, and lipopolysaccharides, induce the production and secretion of AM. Conversely, AM induces the downregulation of inflammatory cytokines in cultured cells. Furthermore, AM downregulates inflammatory processes in a variety of different colitis models, including acetic acid-induced colitis and dextran sulfate sodium-induced colitis. AM exerts antiinflammatory and antibacterial effects and stimulates mucosal regeneration for the maintenance of the colonic epithelial barrier. Here, we describe the first use of AM to treat patients with refractory ulcerative colitis. The results strongly suggest that AM has potential as a new therapeutic agent for the treatment of refractory ulcerative colitis. © 2013 Bentham Science Publishers.
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Gender difference in relationship between body mass index and development of chronic kidney disease 査読あり
Komura H, Nomura I, Kitamura K, Kuwasako K, Kato J
BMC Res Notes 13 463 - 463 2013年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE) - receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes. 査読あり
Sakata K, Hayakawa M, Yano Y, Tamaki N, Yokota N, Eto T, Watanabe R, Hirayama N, Matsuo T, Kuroki K, Sagara S, Mishima O, Koga M, Nagata N, Nishino Y, Kitamura K, Kario K, Takeuchi M, Yamagishi S
Diabetes Metab Res Rev 29 ( 8 ) 624 - 630 2013年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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ストローマからみた心血管病「ストローマをターゲットとした心血管病の治療」 査読あり
鶴田敏博、北村和雄
循環器内科 (Cardioangiology) 74 125 - 131 2013年8月
掲載種別：研究論文（学術雑誌）
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ストローマからみた心血管病 序文 査読あり
北村和雄、鶴田敏博
循環器内科 (Cardioangiology) 74 123 - 124 2013年8月
掲載種別：研究論文（学術雑誌）
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Functions of third extracellular loop and helix 8 of Family B GPCRs complexed with RAMPs and characteristics of their receptor trafficking. 査読あり
Curr Protein Pept Sci
Curr Protein Pept Sci 14 ( 5 ) 416 - 428 2013年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Disruption of cerebellar microzonal organization in GluD2 (Glurδ2) knockout mouse 査読あり
Hashizume M., Miyazaki T., Sakimura K., Watanabe M., Kitamura K., Kano M.
Frontiers in Neural Circuits 7 ( JUL ) 130 2013年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Neural Circuits
Cerebellar cortex has an elaborate rostrocaudal organization comprised of numerous microzones. Purkinje cells (PCs) in the same microzone show synchronous activity of complex spikes (CSs) evoked by excitatory inputs from climbing fibers (CFs) that arise from neurons in the inferior olive (IO). The synchronous CS activity is considered to depend on electrical coupling among IO neurons and anatomical organization of the olivo-cerebellar projection. To determine how the CF-PC wiring contributes to the formation of microzone, we examined the synchronous CS activities between neighboring PCs in the glutamate receptor δ2 knockout (GluD2 KO) mouse in which exuberant surplus CFs make ectopic innervations onto distal dendrites of PCs. We performed in vivo two-photon calcium imaging for PC populations to detect CF inputs. Neighboring PCs in GluD2 KO mice showed higher synchrony of calcium transients than those in wild-type (control) mice. Moreover, the synchrony in GluD2 KO mice hardly declined with mediolateral separation between PCs up to ~200 μm, which was in marked contrast to the falloff of the synchrony in control mice. The enhanced synchrony was only partially affected by the blockade of gap junctional coupling. On the other hand, transverse CF collaterals in GluD2 KO mice extended beyond the border of microzone and formed locally clustered ectopic synapses onto dendrites of neighboring PCs. Furthermore, PCs in GluD2 KO mice exhibited clustered firing (Cf), the characteristic CF response that was not found in PCs of wild-type mice. Importantly, Cf was often associated with localized calcium transients in distal dendrites of PCs, which are likely to contribute to the enhanced synchrony of calcium signals in GluD2 KO mice. Thus, our results indicate that CF signals in GluD2 KO mice propagate across multiple microzones, and that proper formation of longitudinal olivo-cerebellar projection is essential for the spatiotemporal organization of CS activity in the cerebellum. © 2013 Hashizume, Miyazaki, Sakimura, Watanabe, Kitamura and Kano.
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Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. 査読あり
Iwakiri T, Fujimoto S, Kitagawa K, Furuichi K, Yamahana J, Matsuura Y, Yamashita A, Uezono S, Shimao Y, Hisanaga S, Tokura T, Wada T, Kitamura K, Asada Y
BMC Nephrol 14 ( 1 ) 125 - 125 2013年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Reduced fractional shortening of right ventricular outflow tract is associated with adverse outcomes in patients with left ventricular dysfunction. 査読あり
Yamaguchi M, Tsuruda T, Watanabe Y, Onitsuka H, Furukawa K, Ideguchi T, Kawagoe J, Ishikawa T, Kato J, Takenaga M, Kitamura K
Cardiovasc Ultrasound 11 ( 1 ) 19 - 19 2013年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Autocrine effects of neuromedin B stimulate the proliferation of rat primary osteoblasts. 査読あり
Saito H, Nakamachi T, Inoue K, Ikeda R, Kitamura K, Minamino N, Shioda S, Miyata A
J Endocrinol 217 ( 2 ) 141 - 150 2013年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Hepatocyte growth factor activator inhibitor type 1 is a suppressor of intestinal tumorigenesis 査読あり
Hoshiko S., Kawaguchi M., Fukushima T., Haruyama Y., Yorita K., Tanaka H., Seiki M., Inatsu H., Kitamura K., Kataoka H.
Cancer Research 73 ( 8 ) 2659 - 2670 2013年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Research
Hepatocyte growth factor activator inhibitor type 1 (HAI-1/SPINT1) is a membrane-bound serine protease inhibitor expressed on the surface of epithelial cells. Although HAI-1/SPINT1 is abundantly expressed in the intestinal epithelium, its role in intestinal tumorigenesis is not known. In this study, we investigated the role of Hai-1/Spint1 in intestinal tumorigenesis using mouse models. The membranous Hai-1/Spint1 immunoreactivity was decreased in murine ApcMin/+ tumors and also in carcinogen (azoxymethane treatment followed by dextran sodium sulfate administration)-induced colon tumors compared with the adjacent non-neoplastic epithelium. The decreased immunoreactivity appeared to be due to sheddase activity of membrane-type 1 matrix metalloprotease. Then, we examined the effect of intestine-specific deletion of Spint1 gene on ApcMin/+ mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods. Activation of HGF was enhanced in Hai-1/Spint1-deficient ApcMin/+ intestine. Gene expression profiling revealed upregulation of the Wnt/b-catenin signaling circuit, claudin-2 expression, and angiogenesis not only in tumor tissue but also in the background mucosa without macroscopic tumors in Hai-1/Spint1-deficient ApcMin/+ intestine. Intestinal deletion of Spint1 also enhanced the susceptibility to carcinogen-induced colon tumorigenicity of wild-type Apc mice. Our findings suggest that HAI-1/SPINT1 has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli. © 2013 American Association for Cancer Research.