||T. Goto, M. Itoh, T. Suganami, S. Kanai, I. Shirakawa, T. Sakai, M. Asakawa, T. Yoneyama, T. Kai, and Y. Ogawa., Clinicopathogenic and molecular characteristics of synchronous colorectal carcinoma with mismatch repair deficiency., Sci Rep. , 10.1038/s41598-018-26383-8., 8, 1, 8157, 2018.05.
||K. Kawahori, K. Hashimoto, X. Yuan, K. Tsujimoto, N. Hanzawa, M. Hamaguchi, S. Kase, K. Fujita, K. Tagawa, H. Okazawa, Y. Nakajima, N. Shibusawa, M. Yamada, and Y. Ogawa. , Mild maternal hypothyroxinemia during pregnancy induces persistent DNA hypermethylation in the hippocampal brain-derived neurotrophic factor gene in mouse offspring. , Thyroid, 10.1089/thy.2017.0331., 28, 3, 395-406, 2018.03.
||X. Yuan, K. Tsujimoto, K. Hashimoto, K. Kawahori, N. Hanzawa, M. Hamaguchi, T. Seki, M. Nawa, T. Ehara, Y. Kitamura, I. Hatada, M. Konishi, N. Itoh, Y. Nakagawa, H. Shimano, T. Takai-Igarashi, Y. Kamei, and Y. Ogawa., Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood., Nat. Commun., 10.1038/s41467-018-03038-w., 9, e636, 2018.02.
||K. Shiba, K. Tsuchiya, C. Komiya, Y. Miyachi, K. Mori, N. Shimazu, S. Yamaguchi, N. Ogasawara, M. Katoh, M. Itoh, T. Suganami, and Y. Ogawa., Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH. , Sci. Rep. , 8, e2362, 2018.01.
||K. Hashimoto, E. Nishihara, M. Matsumoto, S. Matsumoto, Y. Nakajima, K. Tsujimoto, H. Yamakage, N. Asahara-Satoh, J. Noh, K. Ito, A. Miyauchi, M. Mori, M. Yamada, and Y. Ogawa., Sialic acid-binding immunoglobulin-like lectin1 as a novel predictive biomarker for relapse in Graves’ disease: a multicenter study., Thyroid, 10.1089/thy, 28, 1, 50-59, 2018.01.
||Y. Ogawa, K. Nakao, M. Mukoyama, K. Hosoda, G. Shirakami, H. Arai, Y. Saito, S. I. Suga, M. Jougasaki, H. Imura, Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats
The ventricle is a major site of synthesis and secretion of brain natriuretic peptide, Circulation research, 10.1161/01.RES.69.2.491, 69, 2, 491-500, 1991.01, To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 ± 0.97 pmol/g, which was less than 1% of that in the atrium (451 ± 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 ± 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle>right ventricle>right atrium=left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders..
||M. Mukoyama, K. Nakao, K. Hosoda, S. I. Suga, Y. Saito, Y. Ogawa, G. Shirakami, M. Jougasaki, K. Obata, H. Yasue, Y. Kambayashi, K. Inouye, H. Imura, Brain natriuretic peptide as a novel cardiac hormone in humans
Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide, Journal of Clinical Investigation, 10.1172/JCI115146, 87, 4, 1402-1412, 1991.04, Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 ± 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, Δ((CS-Ao))BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [Δ((AIV-Ao))BNP] was comparable to Δ((CS-Ao))BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than α-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of α-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system..
||Masashi Mukoyama, Kazuwa Nakao, Yoshihiko Saito, Yoshihiro Ogawa, Kiminori Hosoda, Shin Ichi Suga, Gotaro Shirakami, Michihisa Jougasaki, Hiroo Imura, Increased Human Brain Natriuretic Peptide in Congestive Heart Failure, New England Journal of Medicine, 10.1056/NEJM199009133231114, 323, 11, 757-758, 1990.09, To the Editor: Brain natriuretic peptide (BNP), first isolated from the brains of pigs,1 has a striking similarity to atrial natriuretic peptide (ANP) both in structure and in peripheral and central actions.1 2 3 4 BNP is also a cardiac hormone in pigs5 and rats.6,7 Antiserums against porcine or rat BNP, however, failed to detect BNP-like immunoreactivity in human tissues, indicating the structural diversity of BNP among species. Recently, we isolated human BNP from the atrium and determined its 32-amino-acid sequence.8 We have developed a specific radioimmunoassay for human BNP8 with the use of a monoclonal antibody, modeling it on a radioimmunoassay for..
||Yoshihiro Ogawa, Kazuwa Nakao, Masashi Mukoyama, Gotaro Shirakami, Hiroshi Itoh, Kiminori Hosoda, Yoshihiko Saito, Hiroshi Arai, Shin Ichi Suga, Michihisa Jougasaki, Takayuki Yamada, Yoshikazu Kambayashi, Ken Inouye, Hiroo Imura, Rat brain natriuretic peptide — tissue distribution and molecular form —, Endocrinology, 10.1210/endo-126-4-2225, 126, 4, 2225-2227, 1990.04, Using an antiserum against the ring structure of rat brain natriuretic peptide (rat BNP), we have established a specific radioimmunoassay (RIA) for rat BNP and elucidated its tissue distribution and molecular form. Rat BNP-like immunoreactivity (-LI) was detected in the highest amount in cardiac extracts (574.0 ± 138.8 pmol/g in the atrium and 4.3 ± 1.1 pmol/g in the ventricle). The secretory rate of rat BNP-LI from the perfused whole heart was.50.0 ± 1.9 fmol/min, about 60% of which was maintained even after atrial removal. We also detected rat BNP-LI throughout the spinal cord (134-175 fmol/g), although no detectable amount was present (less than 100 fmol/g) in other tissues including the brain. High performance-gel permeation chromatography and reverse phase-high performance liquid chromatography coupled with the RIA revealed that rat BNP with 45 amino acids is a major storage form as well as a secretory form of rat BNP-LI in the heart. The major component in the spinal cord was also rat BNP. These findings indicate that the tissue distribution and the processing pattern of rat BNP are different from those of atrial natriuretic peptide and porcine BNP, thereby suggesting the presence of complicated diversity of the natriuretic peptide system..
||Masashi Mukoyama, Kazuwa Nakao, Yoshihiko Saito, Yoshihiro Ogawa, Kiminori Hosoda, Shin Ichi Suga, Gotaro Shirakami, Michihisa Jougasaki, Hiroo Imura, Human brain natriuretic peptide, a novel cardiac hormone, The Lancet, 10.1016/0140-6736(90)90925-U, 335, 8692, 801-802, 1990.03.