Author: "Tadashi Nakamura" / Topic: male - Searchworks@Jio Institute Digital Library Search Results

164 results on '"Tadashi Nakamura"'

1. Identification and Clinical Associations of 3 Forms of Circulating T-cadherin in Human Serum

Author: Yuya Fujishima, Masahito Iioka, Tadashi Nakamura, Shiro Fukuda, Kazuya Miyashita, Jun Morinaga, Hitoshi Nishizawa, Yuichi Oike, Iichiro Shimomura, Shunbun Kita, Jun Murai, and Norikazu Maeda
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, Type 2 diabetes, Monoclonal antibody, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Japan, Internal medicine, Diabetes mellitus, medicine, Glucose homeostasis, Animals, Humans, Protein Isoforms, Clinical Research Articles, Aged, Adiponectin, adiponectin, diabetes, Cadherin, business.industry, Biochemistry (medical), Middle Aged, medicine.disease, T-cadherin, Cadherins, Rats, 030104 developmental biology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, prodomain, ELISA, Female, business, AcademicSubjects/MED00250, Biomarkers, Blood Chemical Analysis
Abstract: Context T-cadherin (T-cad) is a glycosylphosphatidylinositol (GPI)-anchored cadherin that mediates adiponectin to induce exosome biogenesis and secretion, protect cardiovascular tissues, promote muscle regeneration, and stimulate therapeutic heart protection by transplanted mesenchymal stem cells. CDH13, the gene locus of T-cad, affects plasma adiponectin levels most strongly, in addition to affecting cardiovascular disease risk and glucose homeostasis. Recently, it has been suggested that T-cad exists in human serum, although the details are still unclear. Objective To validate the existence of T-cad forms in human serum and investigate the association with clinical parameters of type 2 diabetes patients. Methods Using newly developed monoclonal antibodies against T-cad, pooled human serum was analyzed, and novel T-cad enzyme-linked immunosorbent assays (ELISAs) were developed. The serum T-cad concentrations of 183 Japanese type 2 diabetes patients were measured in a cross-sectional observational study. The main outcome measure was the existence of soluble T-cad in human serum. Results There were 3 forms of soluble T-cad: a 130-kDa form with a prodomain, a 100-kDa mature form, and a 30-kDa prodomain in human serum. Using newly developed ELISAs to measure them simultaneously, we found that the 130-kDa form of T-cad positively correlated with plasma adiponectin (r = 0.28, P Conclusion We identified 3 novel forms of soluble T-cad. Their importance as disease markers and/or biomarkers of adiponectin function and the possible bioactivity of the respective molecules require further investigation.
Published: 2021

2. Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial

Author: Naoto Katakami, Tomoya Mita, Hidenori Yoshii, Toshihiko Shiraiwa, Tetsuyuki Yasuda, Yosuke Okada, Keiichi Torimoto, Yutaka Umayahara, Hideaki Kaneto, Takeshi Osonoi, Tsunehiko Yamamoto, Nobuichi Kuribayashi, Kazuhisa Maeda, Hiroki Yokoyama, Keisuke Kosugi, Kentaro Ohtoshi, Isao Hayashi, Satoru Sumitani, Mamiko Tsugawa, Kayoko Ryomoto, Hideki Taki, Tadashi Nakamura, Satoshi Kawashima, Yasunori Sato, Hirotaka Watada, Iichiro Shimomura, and On behalf of the UTOPIA study investigators
Subjects: Blood Glucose, Male, lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Time Factors, Arteriosclerosis, Endocrinology, Diabetes and Metabolism, Tofogliflozin, Type 2 diabetes, Pulse Wave Analysis, chemistry.chemical_compound, Vascular Stiffness, Glucosides, Japan, Internal medicine, Diabetes mellitus, medicine, Humans, Prospective Studies, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Pulse wave velocity, Original Investigation, Aged, Glycated Hemoglobin, medicine.diagnostic_test, business.industry, Diabetes, SGLT2 inhibitor, Middle Aged, medicine.disease, Arterial stiffness, Lipids, Treatment Outcome, Blood pressure, Diabetes Mellitus, Type 2, chemistry, lcsh:RC666-701, Cardiology, Female, Glycated hemoglobin, Cardiology and Cardiovascular Medicine, Lipid profile, business, Biomarkers
Abstract: BackgroundTofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease.MethodsThe using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline.ResultsIn a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (– 109.3 [– 184.3, – 34.3] (mean change [95% CI] cm/s,p = 0.005; – 98.3 [– 172.6, – 24.1] cm/s,p = 0.010; – 104.7 [– 177.0, – 32.4] cm/s,p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models.ConclusionsTofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness.Trial RegistrationUMIN000017607. Registered 18 May 2015. (https://www.umin.ac.jp/icdr/index.html)
Published: 2021

3. Amyloid A amyloidosis in a patient with Caplan's syndrome, with special reference to genetic predisposition

Author: Takeshi Yoshinaga, Yasuhiro Morikami, Hiromi Fujii, Naoki Shiraishi, and Tadashi Nakamura
Subjects: Male, Serum Amyloid A Protein, business.industry, Amyloidosis, Comorbidity, medicine.disease, Caplan Syndrome, AA amyloidosis, Rheumatoid arthritis, Immunology, Genetic predisposition, Medicine, Humans, Caplan's syndrome, Genetic Predisposition to Disease, Serum amyloid A, Disease Susceptibility, business, Complication, Biomarkers, Aged
Abstract: Secondary amyloid A (AA) amyloidosis, which is a disorder of protein conformation and metabolism, is an important serious complication of inflammatory diseases, especially rheumatoid arthritis (RA). AA amyloidosis develops when AA fibrils, which are derived from the acute-phase reactant, serum amyloid AA (SAA) protein, in the circulation, are deposited in organs and cause systemic organ dysfunction. Caplan's syndrome, or rheumatoid pneumoconiosis, is a rare type of lung disease in which individuals suffering from RA develop lung nodules that are associated with occupational exposure to silica and coal dust. Confirmation of diagnosing as Caplan's syndrome requires the patient's occupational history, imaging studies, and serology. A 72-year-old male, working as a tunnel construction worker for 38 years, with RA who had both chronic cardiac and renal dysfunction was referred to our hospital. He received a diagnosis of pneumoconiosis about 20 years ago, after which he was also diagnosed with RA. So far we performed medical English literature searches on the combination of Caplan's syndrome with AA amyloidosis; there were no articles in relation to such association. Although RA is one of the most common underlying diseases that occur with AA amyloidosis, our report here is the first description of a case of Caplan's syndrome associated with AA amyloidosis. In this report, we provide details about this rare disease occurring with AA amyloidosis and discuss on the possible pathogenesis of AA amyloidosis from a genetic point of aetiological view.
Published: 2020

4. Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study

Author: Naoto Katakami, Tomoya Mita, Hidenori Yoshii, Toshihiko Shiraiwa, Tetsuyuki Yasuda, Yosuke Okada, Keiichi Torimoto, Yutaka Umayahara, Hideaki Kaneto, Takeshi Osonoi, Tsunehiko Yamamoto, Nobuichi Kuribayashi, Kazuhisa Maeda, Hiroki Yokoyama, Keisuke Kosugi, Kentaro Ohtoshi, Isao Hayashi, Satoru Sumitani, Mamiko Tsugawa, Kayoko Ryomoto, Hideki Taki, Tadashi Nakamura, Satoshi Kawashima, Yasunori Sato, Hirotaka Watada, Iichiro Shimomura, and the UTOPIA study investigators
Subjects: Carotid Artery Diseases, Male, lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Time Factors, Intima-media thickness, Endocrinology, Diabetes and Metabolism, Population, Urology, Tofogliflozin, Type 2 diabetes, Carotid Intima-Media Thickness, chemistry.chemical_compound, Glucosides, Japan, Diabetes mellitus, Internal medicine, Humans, Medicine, Prospective Studies, cardiovascular diseases, Benzhydryl Compounds, education, Sodium-Glucose Transporter 2 Inhibitors, Aged, Original Investigation, education.field_of_study, business.industry, Diabetes, Repeated measures design, SGLT2 inhibitor, Middle Aged, Atherosclerosis, medicine.disease, Treatment Outcome, Blood pressure, Diabetes Mellitus, Type 2, chemistry, lcsh:RC666-701, Disease Progression, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract: BackgroundThis study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT).MethodsThis prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period.ResultsIn a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (− 0.132 mm, SE 0.007; − 0.163 mm, SE 0.013; − 0.170 mm, SE 0.020, respectively) and the control group (− 0.140 mm, SE 0.006; − 0.190 mm, SE 0.012; − 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (− 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (− 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (− 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups.Conclusions/interpretationNo IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population.Clinical Trial RegistrationUMIN000017607 (https://www.umin.ac.jp/icdr/index.html).
Published: 2020

5. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author: Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. 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Subjects: Registrie, Male, Time Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, 030204 cardiovascular system & hematology, Electrocardiography, 0302 clinical medicine, Risk Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, Aged, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, India, Prevalence, Prognosis, Prospective Studies, Survival Rate, Thromboembolism, Registries, Risk Assessment, Medicine, 030212 general & internal medicine, Prospective cohort study, Incidence (epidemiology), cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, Risk assessment, Human, medicine.medical_specialty, Time Factor, RD1-811, Prognosi, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Risk factor, Survival rate, Fibrillation, business.industry, Risk Factor, ta3121, medicine.disease, Clinical trial, Prospective Studie, RC666-701, Surgery, Clinical and Preventive Cardiology, business
Abstract: Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P
Published: 2018

6. Serum-soluble folate receptor β as a biomarker for the activity of rheumatoid arthritis synovitis and the response to anti-TNF agents

Author: Takemasa Matsuda, Takami Matsuyama, Setsuro Komiya, Hideo Otsubo, Yasuhiro Tsuneyoshi, and Tadashi Nakamura
Subjects: Adult, Male, medicine.medical_specialty, Enzyme-Linked Immunosorbent Assay, Osteoarthritis, Gastroenterology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Japan, Rheumatology, Internal medicine, Synovitis, Synovial Fluid, medicine, Humans, Synovial fluid, Folate Receptor 2, Aged, 030203 arthritis & rheumatology, biology, Tumor Necrosis Factor-alpha, business.industry, General Medicine, Middle Aged, medicine.disease, C-Reactive Protein, ROC Curve, Folate receptor, Area Under Curve, Case-Control Studies, 030220 oncology & carcinogenesis, Rheumatoid arthritis, biology.protein, Biomarker (medicine), Female, Antibody, business, Biomarkers
Abstract: This study aims to develop a sandwich ELISA system for the measurement of soluble folate receptor β (sFRβ) and evaluate whether base line levels of serum sFRβ are a biomarker for the activity of RA synovitis and the response to anti-TNF agents. Serum sFRβ from normal controls (41 samples), patients with OA (29 samples), and patients with RA (27 samples) and synovial fluid sFRβ from patients with RA (17 samples) were measured by sandwich ELISA, using anti-FRαβ and anti-FRβ antibodies as capture and detection antibodies, respectively. Baseline levels of serum sFRβ before therapy were evaluated in relation with DAS28-CRP or CRP and response to anti-TNF agents at 3-month follow-up. sFRβ levels in RA synovial fluids were higher than those in RA sera, and sFRβ levels in RA sera were higher than those in osteoarthritis and normal control sera. A significant relationship was observed between serum sFRβ levels and the DAS28-CRP scores or CRP values. The area under curve (AUC) values for receiver-operating characteristic curves defined using the serum sFRβ levels of RA patients before therapy had a higher predictive capacity than DAS28-CRP and CRP for the effective response of anti-TNF agents. The high serum sFRβ levels with a cutoff value of 8 ng/mL were 100% specificity for the effective response of anti-TNF agents. The findings support that the serum sFRβ levels in patients with RA act as a disease activation biomarker and that high serum sFRβ levels act as a predictive biomarker for the response to anti-TNF agents.
Published: 2018

7. Enhancement of the Olfactory Response by Lipocalin Cp-Lip1 in Newt Olfactory Receptor Cells: An Electrophysiological Study

Author: Atsushi Nakamura, Hiroyuki Yamakawa, Ken Sawada, Xing Li, Tatsuo Iwasa, Yoshihiro Noumi, Tadashi Nakamura, Durige Wen, and Xiong Geng
Subjects: 0301 basic medicine, Male, Physiology, Olfactory Receptor Cell, Stimulus (physiology), Lipocalin, law.invention, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Olfactory Mucosa, law, Physiology (medical), medicine, Animals, Electrodes, biology, Dose-Response Relationship, Drug, Chemistry, biology.organism_classification, Salamandridae, Olfactory Bulb, Sensory Systems, Lipocalins, Recombinant Proteins, Cell biology, Electrophysiology, 030104 developmental biology, medicine.anatomical_structure, Odorants, Recombinant DNA, Odorant-binding protein, biology.protein, Female, Single-Cell Analysis, Cynops pyrrhogaster, Olfactory epithelium, 030217 neurology & neurosurgery
Abstract: Previously, we have detected the expression of 2 lipocalin genes (lp1 and lp2) in the olfactory epithelium of the Japanese newt Cynops pyrrhogaster. Recombinant proteins of these genes (Cp-Lip1 and Cp-Lip2, respectively) exhibited high affinities to various odorants, suggesting that they work like the odorant-binding proteins (OBPs). However, the physiological functions of OBP generally remain inconclusive. Here, we examined the effect of Cp-Lip1 on the electrophysiological responses of newt olfactory receptor cells. We observed that the electro-olfactogram induced by the vapor of an odorant with high affinity to Cp-Lip1 appeared to increase in amplitude when a tiny drop of Cp-Lip1 solution was dispersed over the olfactory epithelium. However, the analysis was difficult because of possible interference by intrinsic components in the nasal mucus. We subsequently adopted a mucus-free condition by using suction electrode recordings from isolated olfactory cells, in which impulses were generated by puffs of odorant solution. When various concentration (0–5 µM) of Cp-Lip1 was mixed with the stimulus solution of odorants highly affinitive to Cp-Lip1, the impulse frequency increased in a concentration-dependent manner. The increase by Cp-Lip1 was seen more evidently at lower concentration ranges of stimulus odorants. These results strongly suggest that Cp-Lip1 broadens the sensitivity of the olfactory cells toward the lower concentration of odorants, by which animals can detect very low concentration of odorants.
Published: 2019

8. Serum amyloid A1 (SAA1) gene polymorphisms in Japanese patients with adult-onset Still's disease

Author: Shuzo Sato, Kiyoshi Migita, Toshimasa Shimizu, Hiroshi Furukawa, Tomohiro Koga, Katsumi Eguchi, Hiroshi Watanabe, Atsushi Kawakami, Masataka Umeda, Tomoyuki Asano, Hiroko Kobayashi, Fumiaki Nonaka, Eiji Suzuki, Tadashi Nakamura, Makiko Yashiro, and Yukitaka Ueki
Subjects: Male, MEFV, Observational Study, Disease, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Asian People, Gene Frequency, Japan, Polymorphism (computer science), inflammasome, medicine, Humans, Genetic Predisposition to Disease, Serum amyloid A, Promoter Regions, Genetic, Allele frequency, Gene, Genetic Association Studies, Retrospective Studies, 030203 arthritis & rheumatology, Serum Amyloid A Protein, business.industry, Serum amyloid A1, Inflammasome, serum amyloid A, General Medicine, Middle Aged, Pyrin, Pathophysiology, Immunology, Female, business, polymorphisms, adult-onset still's disease, Still's Disease, Adult-Onset, 030215 immunology, medicine.drug, Research Article
Abstract: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder in which inflammasome activation plays a pathophysiological role. In view of the inflammatory nature of AOSD, we investigated whether serum amyloid A (SAA) gene polymorphisms affect the susceptibility of patients with AOSD. Eighty-seven Japanese patients with AOSD and 200 healthy Japanese subjects were recruited in this study. The genotypes of the -13C/T SNP in the 5′-flanking region of the SAA1 gene (rs12218) and two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined using polymerase chain reaction fragment length polymorphism (PCR-RFLP) assay in all subjects. In AOSD patients, exons 1, 2, 3, and 10 of the MEFV gene were also genotyped by direct sequencing. The frequency of the SAA1.3 allele was increased in AOSD patients compared with that in healthy subjects (43.1% versus 37.5%), but the difference was not significant. The −13T allele was more frequently observed in AOSD patients than in healthy subjects (50.6% versus 41.0%, P = .0336). AOSD patients with the −13T allele had been treated with immunosuppressants more frequently than those without this allele. MEFV mutations were detected in 49 patients with AOSD (49/87, 57.3%). AOSD patients with MEFV variants frequently exhibit macrophage activation syndrome, but the difference was not significant (34.7% versus 18.4%, P = .081). Also, there was no significant difference in SAA1 -13C/T allele frequency between AOSD patients with and without MEFV mutations. Our data shows a significant association between T allele of rs12218 and AOSD in Japanese population.
Published: 2018

9. Clinical and endocrinological characteristics of adrenal incidentaloma in Osaka region, Japan

Author: Keisuke Kosugi, Akihisa Imagawa, Soji Kasayama, Mamiko Tsugawa, Michio Otsuki, Shogo Kurebayashi, Haruhiko Kouhara, Tsunehiko Yamamoto, Tohru Funahashi, Tadashi Nakamura, Iichiro Shimomura, Taka-aki Matsuoka, Hideki Taki, Makoto Ohashi, Ikuo Mineo, Yuya Yamada, Yutaka Umayahara, Kunihiko Hashimoto, and Yukiko Tabuchi
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Adrenal Gland Neoplasms, 030209 endocrinology & metabolism, Pheochromocytoma, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Primary aldosteronism, Japan, Internal medicine, Hyperaldosteronism, medicine, Humans, Aldosterone, Cushing Syndrome, Aged, Retrospective Studies, Subclinical infection, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Retrospective cohort study, Middle Aged, medicine.disease, Positron emission tomography, Abdominal ultrasonography, Female, business, Dyslipidemia
Abstract: The aim of this study was to investigate the clinical and endocrinological characteristics of adrenal incidentalomas in Osaka region, Japan. The study was a multicenter retrospective analysis of 150 patients with adrenal incidentalomas who underwent radiographic and endocrine evaluations between 2005 and 2013. Most adrenal incidentalomas were discovered by computed tomography (77.0%) and the rest were identified by abdominal ultrasonography (14.6%), magnetic resonance imaging (4.2%), or positron emission tomography (4.2%). Adrenal incidentalomas were more frequently localized on the left side than on the right. The average diameter of tumors was 21 ± 11 mm. On endocrinological evaluation, 14 patients were diagnosed with primary aldosteronism (9.3%), 10 with subclinical Cushing's syndrome (6.7%), 7 with pheochromocytoma (4.7%), 7 with Cushing's syndrome (4.7%), 2 with both subclinical Cushing's syndrome and primary aldosteronism (1.3%), and 110 with non-functioning tumors (73.3%). Patients with functioning tumors were significantly younger and had larger tumor diameters than those with non-functioning tumors. Except for hypertension, complications were comparable between patients with functioning and non-functioning tumors, including the presence of glucose intolerance, cardiovascular disease, and dyslipidemia. In conclusion, a higher prevalence of primary aldosteronism was observed compared with a previous report. Complications were comparable between patients with functioning and non-functioning tumors, including the frequencies of glucose intolerance, cardiovascular disease, and dyslipidemia. Long-term follow-up is required in patients with non-functioning tumors because the frequency of complications, such as glucose intolerance, cardiovascular disease, and dyslipidemia, was equal to that in patients with functioning tumors.
Published: 2016

10. Low muscle quality in Japanese type 2 diabetic patients with visceral fat accumulation

Author: Hitoshi Nishizawa, Norikazu Maeda, Iichiro Shimomura, Tohru Funahashi, Masahide Suzuki, Shiro Fukuda, Shinji Yokota, Shunbun Kita, Hirofumi Nagao, Tadashi Nakamura, Yoshimitsu Tanaka, Akihito Otsuka, Hidetoshi Tada, Yasuna Sakai, Yuya Fujishima, Jun Murai, and Mayumi Doi
Subjects: Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Sarcopenia, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Grip strength, 0302 clinical medicine, Japan, Risk Factors, Motor nerve conduction velocity, Prevalence, Adiposity, Original Investigation, Aged, 80 and over, Muscle quality, Hand Strength, Visceral fat accumulation, Middle Aged, Cardiovascular disease, medicine.anatomical_structure, Cardiovascular Diseases, Obesity, Abdominal, Female, Cardiology and Cardiovascular Medicine, Bioelectrical impedance analysis, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Intra-Abdominal Fat, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Humans, Muscle, Skeletal, Angiology, Aged, Skeletal muscle index, business.industry, Skeletal muscle, Odds ratio, medicine.disease, Endocrinology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, lcsh:RC666-701, business
Abstract: Background Although obesity-related type 2 diabetes mellitus (T2DM) and sarcopenia in the elderly have been increasing worldwide, the associations among visceral fat accumulation, skeletal muscle indices (mass, strength, and quality) and cardiovascular diseases in T2DM remain poorly investigated. Methods We enrolled 183 Japanese T2DM inpatients (126 men, 57 women; mean age 64.7 ± 12.6 years, ± SD). The estimated-visceral fat area (eVFA) and skeletal muscle mass were measured by each device using bioelectrical impedance analysis method. We also measured grip strength by dynamometer and motor nerve conduction velocity (MCV). We analyzed the difference in skeletal muscle indices between T2DM patients with and without visceral fat accumulation, and examined the impact of skeletal muscle indices on cardiovascular diseases in patients with visceral fat accumulation. Results The prevalence of sarcopenia defined by the Consensus of Asian Working Group for Sarcopenia and low skeletal muscle mass were both lower in the visceral fat accumulation (+) group than in (−) group. However, the prevalence of weak hand grip strength was similar in the visceral fat accumulation (−) and (+) groups, indicating that considerable patients with visceral fat accumulation had weak grip strength in spite of fair skeletal muscle mass. Muscle quality [grip strength (kg)/arm muscle mass (kg)] was significantly lower in patients with visceral fat accumulation. Multiple regression analysis identified eVFA, MCV and sex as significant and independent determinants of muscle quality. In visceral fat accumulation (+) group, the patients with low muscle quality had longer duration of diabetes, lower eGFR, higher serum adiponectin, lower MCV and higher prevalence of cardiovascular diseases, compared to the patients with high muscle quality. Finally, sex- and age-adjusted models showed significant association between low muscle quality and cardiovascular diseases in all subjects (odds ratio 2.28, p = 0.012), especially in patients with visceral fat accumulation (odds ratio 2.72, p = 0.018). Conclusions T2DM patients with visceral fat accumulation had low muscle quality, and patients with low muscle quality were more affected with cardiovascular diseases. Electronic supplementary material The online version of this article (10.1186/s12933-018-0755-3) contains supplementary material, which is available to authorized users.
Published: 2018

11. Systemic AA amyloidosis secondary to rheumatoid arthritis may be treatable but is still difficult to manage in daily clinical practice

Author: Hiromi Fujii, Tadashi Nakamura, Yasuhiro Morikami, Naoki Shiraishi, and Junichi Kuratsu
Subjects: Male, medicine.medical_specialty, business.industry, Arthritis, Amyloidosis, Middle Aged, medicine.disease, Dermatology, Arthritis, Rheumatoid, Clinical Practice, AA amyloidosis, Rheumatoid arthritis, Internal Medicine, medicine, Humans, Female, business, Complication
Abstract: Systemic AA amyloidosis is a rare, serious and life-threatening complication of chronic inflammatory states, especially rheumatoid arthritis (RA) [1]. Although the frequency of AA amyloidosis has b...
Published: 2019

12. Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still’s disease

Author: Tomoyuki Ito, Naoyuki Tsuchiya, Toshimasa Shimizu, Katsumi Eguchi, Hiromasa Ohira, Eiji Suzuki, Yasumori Izumi, Nozomi Iwanaga, Daisuke Kobayashi, Hiroshi Furukawa, Michio Yasunami, Fumiaki Nonaka, Satoshi Yamasaki, Tomoyuki Asano, Yukitaka Ueki, Atsushi Kawakami, Tomohiro Koga, Hiroko Kobayashi, Keita Fujikawa, Koh-ichiro Yoshiura, Yoshifumi Ubara, Makiko Yashiro, Shigeto Tohma, Kiyoshi Migita, Tadashi Nakamura, Hiroshi Watanabe, Masataka Umeda, and Shuzo Sato
Subjects: 0301 basic medicine, Adult, Male, Autoinflammatory disease, lcsh:Diseases of the musculoskeletal system, Human leukocyte antigen, 03 medical and health sciences, Macrophage-activation syndrome, 0302 clinical medicine, Asian People, Systemic juvenile idiopathic arthritis, Genetic predisposition, Medicine, Humans, Genetic Predisposition to Disease, Allele, HLA-DRB1, Genotyping, Alleles, Aged, 030203 arthritis & rheumatology, Adult onset Still’s disease, business.industry, Odds ratio, Middle Aged, medicine.disease, MEFV, Receptors, TNF-Related Apoptosis-Inducing Ligand, 030104 developmental biology, Macrophage activation syndrome, Immunology, Female, lcsh:RC925-935, business, Still's Disease, Adult-Onset, Research Article, HLA-DRB1 Chains
Abstract: Background HLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still’s disease (AOSD) in a Japanese population by determining the DRB1 allele distributions. Methods DRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing. Results In Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10−6, corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91–4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49–3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18–0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy. Conclusion The DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1406-x) contains supplementary material, which is available to authorized users.
Published: 2017

13. Familial Mediterranean Fever

Author: Fumiaki Nonaka, Yoshikazu Nakamura, Yuka Jiuchi, Tomoko Toma, Hiroshi Furukawa, Akinori Nakamura, Chihiro Terai, Kiyoshi Migita, Masahide Yazaki, Yoshikazu Nakashima, Kazunaga Agematsu, Akihiro Yachie, Michio Yasunami, Ritei Uehara, Atsushi Kawakami, Katsumi Eguchi, Hiroaki Ida, Junya Masumoto, Tadashi Nakamura, and Dai Kishida
Subjects: Adult, Male, myalgia, Abdominal pain, Pathology, medicine.medical_specialty, Genotype, DNA Mutational Analysis, Familial Mediterranean fever, Young Adult, Exon, Asian People, Japan, Prevalence, Humans, Medicine, Original Study, Family history, Genetic Association Studies, business.industry, General Medicine, medicine.disease, MEFV, Health Surveys, Penetrance, Familial Mediterranean Fever, Logistic Models, Phenotype, Mutation, Immunology, Female, medicine.symptom, business
Abstract: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEditerranean FeVer gene (MEFV) mutations. In Japan, patients with FMF have been previously reported, including a mild or incomplete form. Several factors are presumed to contribute to the variable penetrance and to the phenotypic variability of FMF. We conducted the current study to investigate the correlation of variable clinical presentations and MEFV genotypic distributions in Japanese FMF patients. We analyzed demographic, clinical, and genetic data for 311 FMF patients enrolled in the study. Clinically, we classified FMF into 2 phenotypes: 1) the “typical” form of FMF, and 2) the “atypical” form of FMF according to the Tel Hashomer criteria. Patients with the typical FMF phenotype had a higher frequency of febrile episodes, a shorter duration of febrile attacks, more frequent thoracic pain, abdominal pain, a family history of FMF, and MEFV exon 10 mutations. Conversely, patients with the atypical FMF phenotype had a lower frequency of fever episodes and more frequent arthritis in atypical distribution, myalgia, and MEFV exon 3 mutations. Multivariate analysis showed that the variable associated with typical FMF presentation was the presence of MEFV exon 10 mutations. Typical FMF phenotype frequencies were decreased in patients carrying 2 or a single low-penetrance mutations compared with those carrying 2 or a single high-penetrance mutations (M694I), with an opposite trend for the atypical FMF phenotype. In addition, patients having more than 2 MEFV mutations had a younger disease onset and a higher prevalence of thoracic pain than those carrying a single or no mutations. Thus, MEFV exon 10 mutations are associated with the more typical FMF phenotype. In contrast, more than half of the Japanese FMF patients without MEFV exon 10 mutations presented with an atypical FMF phenotype, indicating that Japanese FMF patients tend to be divided into 2 phenotypes by a variation of MEFV mutations.
Published: 2014

14. Amyloid A amyloidosis in a Japanese patient with familial Mediterranean fever associated with homozygosity for the pyrin variant M694I/M694I

Author: Kiyoshi Migita, Tadashi Nakamura, Hirokazu Takaoka, Naoki Shiraishi, Yukio Ando, and Hitoshi Suzushima
Subjects: Male, medicine.medical_specialty, Pathology, Familial Mediterranean fever, Pyrin domain, Gastroenterology, Asian People, Rheumatology, AA amyloidosis, Internal medicine, medicine, Humans, Serum amyloid A, Serum Amyloid A Protein, medicine.diagnostic_test, business.industry, Amyloidosis, Middle Aged, Pyrin, medicine.disease, MEFV, Familial Mediterranean Fever, Cytoskeletal Proteins, Rheumatoid arthritis, Mutation, Renal biopsy, business
Abstract: Familial Mediterranean fever (FMF) is an autoinflammatory disease common in eastern Mediterranean populations. The most severe complication is the development of secondary amyloid A (AA) amyloidosis. A 51-year-old Japanese male who had been suffering from periodic fever since in his twenties was referred to our hospital for proteinuria. Histological findings from renal biopsy revealed the deposition of AA amyloid fibrils, suggesting that renal dysfunction was due to AA amyloidosis. Gene analysis of the patient and his mother showed that both were homozygous for the M694I mutation in the MEFV gene. His mother was also a carrier of the SAA1.3 allele, which is not only a univariate predictor of survival but also a risk factor for the association of AA amyloidosis with rheumatoid arthritis in Japanese patients, and the SAA1-13T allele in the 13T/C polymorphism on the 5′-flanking region of the SAA1 gene. The patient was also a carrier of the SAA-13T allele. Colchicine resulted in not only an amelioration of the acute febrile attacks of FMF inflammation, but also an improvement in kidney dysfunction due to AA amyloidosis.
Published: 2014

15. Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis

Author: Minoru Nakamura, T Sakai, M Izumi, Hideko Kozuru, Yasumori Izumi, Tadashi Nakamura, Yuka Jiuchi, Chieko Kawahara, Satoru Motokawa, Kiyoshi Migita, and A. Kawakami
Subjects: Adult, Male, Antimetabolites, Antineoplastic, medicine.medical_specialty, Immunology, Anti-Inflammatory Agents, Down-Regulation, Arthritis, Rheumatoid, Placebos, Double-Blind Method, Piperidines, Internal medicine, Humans, Immunology and Allergy, Medicine, Pyrroles, Serum amyloid A, Interleukin 6, Protein Kinase Inhibitors, Serum Amyloid A Protein, Janus kinase inhibitor, Tofacitinib, biology, Interleukin-6, business.industry, Janus Kinase 3, Interleukin, Original Articles, Middle Aged, medicine.disease, Receptors, Interleukin-6, C-Reactive Protein, Methotrexate, Pyrimidines, Endocrinology, Rheumatoid arthritis, biology.protein, Female, business, Janus kinase
Abstract: Summary The Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 μg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 μg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib down-regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib.
Published: 2014

16. Severe tardive dyskinesia induced by domperidone in presenile and non-dementia type 2 diabetes man with alcohol misuse showing albuminocytological dissociation and white matter hyperintensity

Author: Tadashi Nakamura, Akinori Kanzaki, Hidetoshi Tada, and Akihito Otsuka
Subjects: Male, medicine.medical_specialty, Dissociation (neuropsychology), Alcohol, Type 2 diabetes, Tardive dyskinesia, Gastroenterology, Diagnosis, Differential, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, otorhinolaryngologic diseases, medicine, Humans, Tardive Dyskinesia, Dementia, Unexpected Outcome (Positive or Negative) Including Adverse Drug Reactions, business.industry, 030206 dentistry, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, Domperidone, Alcoholism, Diabetes Mellitus, Type 2, White matter hyperintensity, chemistry, Blood-Brain Barrier, Dopamine Antagonists, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Domperidone has difficulty passing the blood–brain barrier, thus rarely causes tardive dyskinesia. Furthermore, its symptoms in adults are generally mild. Although both alcohol and diabetes are thought to increase the risk of development of tardive dyskinesia, their impact remains controversial, especially diabetes, and factors related to worsened tardive dyskinesia have not been clearly elucidated. A 59-year-old man with type 2 diabetes and history of alcohol misuse, who had been chronically prescribed domperidone at 15 mg/day, showed severe tardive dyskinesia, which was remitted within several days by stopping the drug. In our case, albuminocytological dissociation and white matter hyperintensity on MRI were confirmed, which were thought to be related to blood–brain barrier dysfunction. This present findings indicate that alcohol misuse and type 2 diabetes, as well as albuminocytological dissociation and white matter hyperintensity may result in severe tardive dyskinesia, even in individuals receiving domperidone.
Published: 2019

17. Potential of a 70 kDa IL-10-like factor in synovial fluid from rheumatoid arthritis patients to augment superoxide generation by human neutrophils

Author: Tetsuro Yamamoto and Tadashi Nakamura
Subjects: Male, Hot Temperature, Time Factors, Neutrophils, medicine.drug_class, Monoclonal antibody, Arthritis, Rheumatoid, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rheumatology, Superoxides, Synovial Fluid, Humans, Medicine, Synovial fluid, Cytochalasin, 030212 general & internal medicine, Cytochalasin B, Cells, Cultured, Chromatography, High Pressure Liquid, Aged, Aged, 80 and over, 030203 arthritis & rheumatology, Protein Stability, business.industry, Superoxide, Antibodies, Monoclonal, Proteins, Interleukin, hemic and immune systems, Biological activity, Middle Aged, Molecular biology, Interleukin-10, Up-Regulation, Molecular Weight, Interleukin 10, chemistry, Proteolysis, Immunology, Chromatography, Gel, Female, Isoelectric Focusing, business, Peptide Hydrolases, Signal Transduction
Abstract: Aim To elucidate the role of polymorphonuclear leukocytes (PMNs) in joint destruction during the inflammatory process in rheumatoid arthritis (RA) as related to superoxide generation. Methods Superoxide generation by human peripheral PMNs was measured by using a water-soluble formazan dye, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt, under PMN stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP) and cytochalasin B. Factors in synovial fluids (SF) from RA patients that may augment PMN superoxide generation were characterized via high-performance liquid chromatography and isoelectric focusing. Results The formazan dye allowed measurement of superoxide generated in the xanthine-xanthine oxidase system and by PMNs stimulated by cytochalasin B and fMLP in the presence of the intermediate electron transporter phenazine methosulfate. By using chromatography and electrophoresis, an RA-SF protein with an apparent molecular size of 70 kDa and an isoelectric point of 8.3 was isolated and was demonstrated to increase superoxide generation by PMNs. The factor was heat-labile and susceptible to protease treatment. This enhancing activity of the factor was absorbed by human PMNs and was somewhat immunoadsorbed with a specific monoclonal antibody against interleukin (IL)-10. Conclusion The 70-kDa protein factor in RA-SF increased superoxide generation by human PMNs, which suggests the possibility of its being related to IL-10. This factor may have a pathological role in RA joint destruction caused by PMNs and coinciding with rheumatoid inflammation, which suggests that PMNs, via superoxide generation, play an important role in RA joint destruction. IL-10 therefore likely has biological activity toward PMNs during synovial inflammatory chain reactions in RA.
Published: 2013

18. Carotid intima-media thickness, but not visceral fat area or adiponectin, correlates with intracoronary stenosis detected by multislice computed tomography in people with type 2 diabetes and hypertension

Author: Tadashi Nakamura, Yohei Kuroda, Tohru Funahashi, Iichiro Shimomura, Masahiro Kumada, Keita Yamasaki, Kenichi Tsujii, Yasuhiko Nakagawa, Satoru Sumitsuji, Kouichi Tachibana, Hideaki Nakatsuji, Yuhei Nojima, Yukiyoshi Okauchi, Tomoko Nakanishi-Minami, and Ken Kishida
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Intra-Abdominal Fat, Carotid Intima-Media Thickness, Endocrinology, Internal medicine, Diabetes mellitus, Multidetector Computed Tomography, Internal Medicine, medicine, Humans, Visceral fat, Aged, Adiponectin, business.industry, Coronary Stenosis, General Medicine, Multislice computed tomography, Middle Aged, medicine.disease, Stenosis, Candesartan, Diabetes Mellitus, Type 2, Intima-media thickness, Hypertension, Cardiology, Female, Radiology, business, medicine.drug
Abstract: We investigated the relationship between intracoronary stenosis detected by multislice computed tomography and various clinical parameters in type 2 diabetic patients with hypertension treated with candesartan ( n =42). The results showed that carotid intima-media thickness, but not visceral fat area or adiponectin, correlated significantly with intracoronary stenosis ( p
Published: 2012

19. Short-term intervention reduces bioelectrical impedance analysis-measured visceral fat in type 2 diabetes mellitus

Author: Tohru Funahashi, Miwa Ryo, Iichiro Shimomura, Tadashi Nakamura, and Ken Kishida
Subjects: Male, medicine.medical_specialty, Time Factors, Waist, Endocrinology, Diabetes and Metabolism, Calorie restriction, Intra-Abdominal Fat, Endocrinology, Risk Factors, Weight loss, Classification of obesity, Diabetes mellitus, Internal medicine, Electric Impedance, Internal Medicine, medicine, Humans, Obesity, Exercise, Visceral fat, Caloric Restriction, business.industry, Body Weight, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Diet, Diabetes Mellitus, Type 2, Cardiology, Female, Waist Circumference, medicine.symptom, Energy Intake, business, Bioelectrical impedance analysis, Follow-Up Studies
Abstract: In 25 patients with Type 2 diabetes mellitus, the short-term in-hospital calorie restriction combined with moderate exercise reduced visceral fat. The reduction of visceral fat can improve metabolic cardiovascular risk factors, while the reductions in body weight and waist circumference were small and reduction in subcutaneous fat was not significant.
Published: 2014

20. Urgency Is an Independent Factor for Sleep Disturbance in Men with Obstructive Sleep Apnea

Author: Akira Tsujimura, Norio Nonomura, Nakamori Suganuma, Akihiko Okuyama, Yoshiro Sugita, Takayuki Kumano-go, Yasushi Miyagawa, Tetsuya Takao, Jiro Nakayama, Hiroshi Kiuchi, Shinichiro Fukuhara, Keisuke Yamamoto, and Tadashi Nakamura
Subjects: Male, medicine.medical_specialty, Polysomnography, Urology, Comorbidity, urologic and male genital diseases, Severity of Illness Index, Internal medicine, medicine, Humans, Nocturia, Aged, Sleep Apnea, Obstructive, Sleep disorder, medicine.diagnostic_test, Urinary Bladder, Overactive, business.industry, Apnea, Sleep apnea, Urinary Incontinence, Urge, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Surgery, Obstructive sleep apnea, Sleep Disorders, Intrinsic, Overactive bladder, medicine.symptom, business, Hypopnea
Abstract: OBJECTIVES The relationship between overactive bladder (OAB) symptoms, other than nocturia, and sleep, has not been fully evaluated, although a close relationship between nocturia and sleep disturbance has been reported. In the present study, we evaluated the relationship between OAB symptoms and several polysomnography (PSG) parameters in middle-age men with sleep disturbance, especially to clarify whether urgency as the hallmark symptom of an OAB is independently associated with sleep quality. METHODS A total of 32 men >40 years of age (mean age 58.0 ± 12.6), who had been diagnosed with obstructive sleep apnea syndrome by PSG, were included in the present study. Their OAB symptoms were evaluated using the OAB symptom score (OABSS) before PSG. The relationship between the OABSS and several parameters, such as sleeping time, sleeping efficiency, sleep latency, percentage of rapid eye movement during sleeping time, and apnea/hypopnea index obtained from PSG, was evaluated. RESULTS Multivariate analysis showed that only sleeping efficiency was an influencing factor on the total OABSS. Of the 4 subscores of OABSS, including frequency, nocturia, urgency, and urgency incontinence, multivariate analysis showed that the subscores of nocturia and urgency were independent influencing factors on sleeping efficiency. Nocturia correlated negatively with sleeping efficiency (Pearson's correlation 0.533, P
Published: 2010

21. Etanercept can induce resolution of renal deterioration in patients with amyloid A amyloidosis secondary to rheumatoid arthritis

Author: Syu-ichi Higashi, Michishi Tsukano, Kunihiko Tomoda, Tadashi Nakamura, and Masahiro Shono
Subjects: Male, medicine.medical_specialty, Genotype, Renal function, Gastroenterology, Receptors, Tumor Necrosis Factor, Etanercept, Arthritis, Rheumatoid, chemistry.chemical_compound, Japan, Rheumatology, AA amyloidosis, Internal medicine, medicine, Humans, Renal Insufficiency, Serum amyloid A, Serum Amyloid A Protein, Aged, Creatinine, Proteinuria, business.industry, Amyloidosis, Anti-Inflammatory Agents, Non-Steroidal, General Medicine, Middle Aged, medicine.disease, stomatognathic diseases, Endocrinology, chemistry, Immunoglobulin G, Female, medicine.symptom, business, medicine.drug
Abstract: The benefit of biological therapies in rheumatoid arthritis (RA) treatment is well known, but their role in amyloid A (AA) amyloidosis secondary to RA is unclear. The aim of this study was to clarify the clinical benefit of etanercept in RA patients with AA amyloidosis. We treated 14 RA patients who had serum amyloid A protein (SAA) 1.3 allele, with biopsy-confirmed AA amyloidosis with etanercept and investigated the efficacy of etanercept treatment, focusing on renal function retrospectively. The AA amyloidosis improved and stabilized after 89.1 ± 27.2 weeks. Proteinuria decreased from 2.24 ± 0.81 to 0.57 ± 0.41 g/day (P < 0.01) and SAA fell from 250 ± 129 to 26 ± 15μg/ml (P < 0.01), respectively. Diarrhea secondary to gastrointestinal AA amyloidosis was less. Overall, the serum creatinine levels did not benefit with treatment, but in those with a creatinine values
Published: 2010

22. Characteristics of sleep-disordered breathing in Japanese patients with type 2 diabetes mellitus

Author: Iichiro Shimomura, Ken Kishida, Yuji Matsuzawa, Tohru Funahashi, Michio Otuki, Kohei Okita, Yasuhiko Nakagawa, Tadashi Nakamura, Hiromi Iwahashi, Shinji Kihara, and Susumu Kashine
Subjects: Adult, Male, medicine.medical_specialty, Central sleep apnea, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Statistics, Nonparametric, Endocrinology, Japan, Internal medicine, Diabetes mellitus, Natriuretic Peptide, Brain, Prevalence, medicine, Natriuretic peptide, Humans, cardiovascular diseases, Aged, Ultrasonography, Glycated Hemoglobin, Adiponectin, business.industry, Sleep apnea, Type 2 Diabetes Mellitus, Middle Aged, medicine.disease, Brain natriuretic peptide, Sleep Apnea, Central, nervous system diseases, respiratory tract diseases, Adipose Tissue, Diabetes Mellitus, Type 2, Female, Tunica Intima, business, Body mass index
Abstract: Sleep-disordered breathing (SDB), especially sleep apnea-hypopnea syndrome, is often observed in patients with type 2 diabetes mellitus; but there are only a few studies on SDB in Japanese diabetic subjects. We investigated the prevalence of SDB in diabetic patients; associations between severity of sleep apnea (SA) and clinical factors, visceral fat, and adiponectin; and associations between type of SA and clinical factors. In the present study, 40 Japanese diabetic patients underwent overnight cardiorespiratory monitoring, and night and morning measurements of serum adiponectin concentrations. Sleep apnea was detected in Japanese diabetic patients at a high prevalence (77.5%). The following variables were associated with SDB: age, body mass index, estimated visceral fat area, and nocturnal reduction in serum adiponectin concentrations. The prevalence of central sleep apnea (CSA, >or=5/h) was 32.3% among diabetic SDB patients. Diabetic SDB patients with CSA had higher hemoglobin, increased intima-media thickness, and higher plasma brain natriuretic peptide levels than those without CSA (
Published: 2010

23. A Case of Adolescent Hyperlipoproteinemia with Xanthoma and Acute Pancreatitis, Associated with Decreased Activities of Lipoprotein Lipase and Hepatic Triglyceride Lipase

Author: Motoko Omura, Tohru Funahashi, Taku Yamamura, Iichiro Shimomura, Shinji Kihara, Tadashi Nakamura, Norikazu Maeda, Hiromi Iwahashi, Junji Kozawa, Kohji Shirai, Kakeyoshi Murano, Kohei Okita, Koichi Fujita, and Masato Ishigami
Subjects: Male, Hyperlipoproteinemias, Very low-density lipoprotein, medicine.medical_specialty, Adolescent, Internal medicine, Xanthomatosis, Internal Medicine, medicine, Humans, Lipoprotein lipase, Triglyceride lipase, Bezafibrate, medicine.diagnostic_test, business.industry, digestive, oral, and skin physiology, Hypertriglyceridemia, nutritional and metabolic diseases, Lipase, General Medicine, medicine.disease, Lipoprotein Lipase, Endocrinology, Liver, Pancreatitis, Acute Disease, lipids (amino acids, peptides, and proteins), business, Lipid profile, Chylomicron, medicine.drug, Lipoprotein
Abstract: Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) enhance the hydrolysis of triglycerides (TG) transported by chylomicron (CM) and very-low-density lipoprotein (VLDL). We report a case of severe hyperchylomicronemia with high levels of remnant lipoprotein and total cholesterol (T-Chol) in a 15-year-old boy. Precise examination of the lipid profile showed decreased activities of both LPL and HTGL, although the protein mass for LPL and HTGL were maintained. In addition, bezafibrate treatment effectively ameliorated hypertriglyceridemia in this case. This is the first case of hyperchylomicronemia with decreased activities and unaffected protein masses for both LPL and HTGL, without overt immuno-dysfunction.
Published: 2010

24. Visceral Obesity and Hypoadiponectinemia are Significant Determinants of Hepatic Dysfunction

Author: Yoshihiro Kamada, Tohru Funahashi, Norio Hayashi, Tadashi Nakamura, Shinichi Kiso, Miwa Ryo, Yukiyoshi Okauchi, Juichi Fukushima, Yuichi Yoshida, Hitoshi Nishizawa, and Iichiro Shimomura
Subjects: Adult, Male, medicine.medical_specialty, Aspartate transaminase, Intra-Abdominal Fat, Asymptomatic, Sex Factors, Japan, Liver Function Tests, Nephelometry and Turbidimetry, Internal medicine, Electric Impedance, medicine, Humans, Aspartate Aminotransferases, Obesity, Gamma-glutamyltransferase, biology, Adiponectin, business.industry, Gastroenterology, Alanine Transaminase, gamma-Glutamyltransferase, Middle Aged, medicine.disease, Cross-Sectional Studies, Endocrinology, Liver, Alanine transaminase, biology.protein, Regression Analysis, Female, Liver function, medicine.symptom, business, Bioelectrical impedance analysis
Abstract: BACKGROUND AND AIM Adiponectin is an anti-inflammatory and insulin-sensitizing adipocytokine, and its serum concentrations are reduced in obesity with visceral fat accumulation. Visceral fat accumulation is an independent determinant of elevated serum liver enzymes. Hypoadiponectinemia plays important roles in the clinical progression of nonalcoholic steatohepatitis. The aim of this study was to evaluate the relation between visceral fat area (VFA), serum adiponectin concentration, and biochemical liver tests, such as aspartate aminotransferase, alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) in normal subjects. METHODS The study group comprised 3827 Japanese subjects [mean age+/-SD; 47.6+/-10.7 y: 2854 males (48.4+/-10.7 y), 973 females (45.3+/-10.1 y)], who underwent annual health checkup in 2004. In addition to parameters measured in the annual health checkup, VFA and serum adiponectin concentration were measured by the bioelectrical impedance analysis method and a latex particle-enhanced turbidimetric assay system, respectively. RESULTS Pearson's correlation analysis showed a significant correlation between VFA and the levels of the above 3 liver enzymes in both sexes, and a significant negative correlation between adiponectin and all biochemical liver tests in men and with ALT and GGT in women. Stepwise multiple regression analysis showed that VFA was a significant determinant of serum liver tests in both sexes. Moreover, serum adiponectin concentration significantly and negatively influenced male ALT and GGT and female GGT. CONCLUSIONS Both visceral obesity and hypoadiponectinemia are significant determinants of subtle and asymptomatic hepatic dysfunction in normal Japanese subjects.
Published: 2009

25. Nocturnal reduction in circulating adiponectin concentrations related to hypoxic stress in severe obstructive sleep apnea-hypopnea syndrome

Author: Hitoshi Nishizawa, Ken Kishida, Tohru Funahashi, Ryoko Yoshida, Shinji Kihara, Mina Sonoda, Ayumu Hirata, Atsutaka Yasui, Yasuhiko Nakagawa, Tadashi Nakamura, and Iichiro Shimomura
Subjects: Adult, Male, medicine.medical_specialty, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Gene Expression, Adipokine, Severity of Illness Index, Mice, Stress, Physiological, 3T3-L1 Cells, Physiology (medical), Internal medicine, medicine, Animals, Humans, Continuous positive airway pressure, Hypoxia, Sleep Apnea, Obstructive, Continuous Positive Airway Pressure, Adiponectin, business.industry, Respiratory disease, Sleep apnea, Middle Aged, Hypoxia (medical), medicine.disease, Circadian Rhythm, Mice, Inbred C57BL, Obstructive sleep apnea, Endocrinology, Female, medicine.symptom, business, Hypopnea, hormones, hormone substitutes, and hormone antagonists
Abstract: Previous reports demonstrated that adiponectin has antiatherosclerotic properties. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is reported to exacerbate atherosclerotic diseases. We investigated nocturnal alternation of serum adiponectin levels before sleep and after wake-up in OSAHS patients and the effect of sustained hypoxia on adiponectin in vivo and in vitro. We measured serum adiponectin concentrations in 75 OSAHS patients and 18 control subjects before sleep and after wake-up and examined the effect of one-night nasal continuous positive airway pressure (nCPAP) on adiponectin in 24 severe OSAHS patients. We investigated the effects of hypoxia on adiponectin in mice and cultured adipocytes with a sustained hypoxia model. Circulating adiponectin levels before sleep and after wake-up were lower in severe OSAHS patients than in control subjects [before sleep: 5.9 ± 2.9 vs. 8.8 ± 5.6 μg/ml ( P < 0.05); after wake-up: 5.2 ± 2.6 vs. 8.5 ± 5.5 μg/ml ( P < 0.01), respectively; means ± SD]. Serum adiponectin levels diminished significantly during sleep in severe OSAHS patients ( P < 0.0001), but one-night nCPAP improved the drop in serum adiponectin levels [−18.4 ± 13.4% vs. −10.4 ± 12.4% ( P < 0.05)]. In C57BL/6J mice and 3T3-L1 adipocytes, hypoxic exposure decreased adiponectin concentrations by inhibiting adiponectin regulatory mechanisms at secretion and transcriptional levels. The present study demonstrates nocturnal reduction in circulating adiponectin levels in severe OSAHS. Our experimental studies showed that hypoxic stress induced adiponectin dysregulation at transcriptional and posttranscriptional levels. Hypoxic stress is, at least partly, responsible for the reduction of serum adiponectin in severe OSAHS. Nocturnal reduction in adiponectin in severe OSAHS may be an important risk for cardiovascular events or other OSAHS-related diseases during sleep.
Published: 2008

26. Prolongation of Intrathecal and Sciatic Nerve Blocks Using a Complex of Levobupivacaine with Maltosyl-β-Cyclodextrin in Rats

Author: Masahiko Taniguchi, Mitsuru Irikura, Mayumi Takasaki, Tadashi Nakamura, Kanako Matsuo, Ken Karashima, and Tetsumi Irie
Subjects: Male, Time Factors, medicine.drug_class, Intrathecal, Anesthesia, Spinal, Rats, Sprague-Dawley, Muscle tone, medicine, Animals, Maltose, Injections, Spinal, Levobupivacaine, chemistry.chemical_classification, Cyclodextrins, Cyclodextrin, Local anesthetic, business.industry, Nerve Block, Bupivacaine, Sciatic Nerve, Rats, Drug Combinations, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Nociception, chemistry, Anesthesia, Anesthetic, Sciatic nerve, business, medicine.drug
Abstract: BACKGROUND We used a cyclodextrin-based drug delivery system, consisting of levobupivacaine complexed with maltosyl-beta-cyclodextrin (G2-beta-CD), in spinal and sciatic nerve blocks in rats to investigate prolongation of the local anesthetic effect. METHODS Rats were assigned to four groups (n = 6 in each) and received intrathecally 30 microL of 1% levobupivacaine complexed with 0 (control), 50, 100, or 200 mM of G2-beta-CD. Muscle tone and tail flick latency were studied after intrathecal administration. Four more groups (n = 6) of rats received a sciatic nerve block with 0.5% or 1% levobupivacaine complexed with either 0 or 100 mM of G2-beta-CD. The time course of changes in proprioception, motor function, and nociception after circumferential subcutaneous administration to the sciatic nerve was examined. RESULTS With the intrathecal block, all rats stopped tail movement immediately after injection of the local anesthetic. The mean time to recovery of muscle tone with 1% levobupivacaine complexed with 100 mM (80.0 +/- 8.9 min) and 200 mM (91.7 +/- 7.0 min) of G2-beta-CD was significantly longer than that of the control group (38.3 +/- 3.1 min), but tail flick latency was not prolonged. With the sciatic nerve block, all rats were temporarily immobilized after levobupivacaine injection. The anesthetic effects of 0.5% levobupivacaine with 100 mM of G2-beta-CD were twice as long as those for 0.5% levobupivacaine alone, and those of 1% levobupivacaine with 100 mM of G2-beta-CD were 1.4 times longer than those for 1% levobupivacaine alone. CONCLUSIONS The complex of levobupivacaine with G2-beta-CD prolonged the anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks in rats.
Published: 2007

27. CD8+ T lymphocytes infiltrate predominantly in the inflammatory foci of MPO-ANCA-positive thoracic hypertrophic pachymeningitis in a patient with HLA-A24

Author: Kunihiko Tomoda, Kei Hirakawa, Terumi Sakae, Tadashi Nakamura, Ken-ichi Iyama, Michishi Tsukano, and Syu-ichi Higashi
Subjects: Male, Pathology, medicine.medical_specialty, Dura mater, HLA-A24 Antigen, Human leukocyte antigen, CD8-Positive T-Lymphocytes, medicine.disease_cause, Antibodies, Antineutrophil Cytoplasmic, Autoimmunity, Rheumatology, Adrenal Cortex Hormones, Humans, Cytotoxic T cell, Medicine, Meningitis, Aseptic, Aged, Peroxidase, HLA-A Antigens, business.industry, Laminectomy, Autoantibody, Interleukin, Middle Aged, medicine.disease, Radiography, medicine.anatomical_structure, Spinal Cord, Immunology, Female, Dura Mater, business, Vasculitis, Immunosuppressive Agents, CD8
Abstract: Hypertrophic pachymeningitis (HP) is extremely rare and an inflammatory process that thickens the dura mater. A 59-year-old Japanese woman developed backache, became paraplegic, and magnetic resonance imaging revealed diffuse thickening of the thoracic dura mater encompassing the spinal cord. Although a test for myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) was shown to be positive, vasculitis was not found and CD8(+) T lymphocytes that predominated in the inflammatory foci. Both interleukin (IL)-2 and IL-6 were markedly elevated in not only sera but also cerebrospinal fluids, very much higher in the latter. Human leukocyte antigen (HLA) typing revealed A24 positivity, suggesting this molecule was interacting with CD8(+) T lymphocytes. It was suggested that immunological disharmony and autoimmunity would play a pivotal role in the development of HP under genetic background of HLA-A24, and HP would be one feature of multiple organ involvement in ANCA-associated diseases.
Published: 2007

28. Comment on: Dysregulated mature IL-1β production in familial Mediterranean fever: reply

Author: Yoshika Tsuji, Kiyoshi Migita, and Tadashi Nakamura
Subjects: Male, medicine.medical_specialty, Serum Amyloid A Protein, business.industry, Interleukin-1beta, Familial Mediterranean fever, medicine.disease, Familial Mediterranean Fever, Endocrinology, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Female, business
Published: 2015

29. Association of human leukocyte antigen alleles with chronic lung diseases in rheumatoid arthritis

Author: Shouhei Nagaoka, Naoyuki Tsuchiya, Hiroshi Furukawa, Kiyoshi Migita, Akiko Komiya, Shomi Oka, Tadashi Nakamura, Shinichiro Tsunoda, Naoshi Fukui, Akiko Suda, Masao Katayama, Atsushi Hashimoto, Shoji Sugii, Satoshi Ito, Kota Shimada, Shigeto Tohma, Koichiro Saisho, and Hajime Sano
Subjects: 0301 basic medicine, Male, Human leukocyte antigen, Serology, Arthritis, Rheumatoid, 03 medical and health sciences, Epitopes, 0302 clinical medicine, Rheumatology, Usual interstitial pneumonia, medicine, Odds Ratio, HLA-DQ beta-Chains, Humans, Pharmacology (medical), Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Genetic association, Aged, 030203 arthritis & rheumatology, Lung, business.industry, Interstitial lung disease, Odds ratio, Middle Aged, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Phenotype, Pulmonary Emphysema, Rheumatoid arthritis, Immunology, Female, business, Lung Diseases, Interstitial, HLA-DRB1 Chains
Abstract: OBJECTIVES Chronic lung diseases including interstitial lung disease and airway disease (AD) occur in RA patients. Interstitial lung disease and AD in RA are extra-articular manifestations that influence the prognosis quoad vitam of RA. Studies on associations of HLA alleles with RA have been carried out, and shared epitopes of several alleles are reported to be associated with RA susceptibility. Few association studies in RA subpopulations with chronic lung diseases have been conducted. The aim of the study was to identify HLA alleles predisposing to RA phenotypes including the presence of AD. METHODS Associations of HLA-DRB1 and DQB1 alleles with chronic lung diseases in RA were analysed. RESULTS A positive association was found between the DR4 serological group and resistance to usual interstitial pneumonia [P = 0.0250, odds ratio (OR) 0.62, 95% CI: 0.41, 0.93]. The DR2 serological group was associated with susceptibility to usual interstitial pneumonia (P = 0.0036, OR = 1.86, 95% CI: 1.23, 2.81). An association was found for shared epitopes alleles with bronchiolitic AD (P = 0.0040, OR = 2.06, 95% CI: 1.24, 3.41). DQB1*03:01 was associated with bronchiectatic AD (P = 0.0021, corrected P-value (Pc) = 0.0315, OR = 1.99, 95% CI: 1.30, 3.06), as well as with emphysema (P = 0.0007, Pc = 0.0104, OR = 2.43, 95% CI: 1.49, 3.95). In combined analysis, a predisposing association of DQB1*03:01 (P = 1.94 ×10(-5), Pc = 0.0003, OR = 2.16, 95% CI: 1.53, 3.06) and a negative association of DQB1*03:02 (P = 0.0008, Pc = 0.0117, OR = 0.33, 95% CI: 0.17, 0.67) with bronchiectatic AD or emphysema were observed in RA. CONCLUSION The present study identified an association of HLA-DQB1*03:01 with predisposition to, and DQB1*03:02 with resistance to, bronchiectatic AD or emphysema in RA.
Published: 2015

30. Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever

Author: Kiyoshi Migita, Dai Kishida, Tomoko Toma, Masahide Yazaki, Tomohiro Koga, Kazunaga Agematsu, Hiroaki Ida, Akihiro Yachie, A Kawakami, Katsumi Eguchi, Hitomi Nakamura, Michio Yasunami, Hiroshi Furukawa, Tadashi Nakamura, Junya Masumoto, Minoru Nakamura, and Akinori Nakamura
Subjects: Adult, Male, Adolescent, Genotype, Familial Mediterranean fever, Genes, MHC Class I, lcsh:Medicine, Human leukocyte antigen, Biology, Young Adult, Asian People, Japan, medicine, HLA-B Antigens, Humans, Allele, Child, lcsh:Science, Multidisciplinary, Polymorphism, Genetic, lcsh:R, Odds ratio, Middle Aged, Pyrin, MEFV, medicine.disease, Penetrance, Familial Mediterranean Fever, Cytoskeletal Proteins, Immunology, Mutation, Female, lcsh:Q, Research Article, HLA-DRB1 Chains
Abstract: ObjectivesThe genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes.MethodsGenotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment.ResultsThe carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni’s correction for multiple statistical tests (n = 28, pConclusionsThe differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations., Article, PLOS ONE.10(5):e0125938(2015)
Published: 2015

31. Familial massive tendon xanthomatosis with decreased high-density lipoprotein–mediated cholesterol efflux

Author: Ken-ichi Hirano, Akifumi Matsuyama, Ryutaro Komuro, Naohiko Sakai, Shizuya Yamashita, Fumihiko Matsuura, Tohru Ohama, Tadashi Nakamura, Masahiro Koseki, Kenichi Tsujii, Hisatoyo Hiraoka, and Makoto Nishida
Subjects: Male, Proband, medicine.medical_specialty, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Xanthoma, Achilles Tendon, Monocytes, chemistry.chemical_compound, Endocrinology, High-density lipoprotein, Internal medicine, medicine, Humans, Cells, Cultured, Apolipoprotein A-I, biology, Cholesterol, Macrophages, Wolman Disease, Lipoproteins, HDL3, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Pedigree, chemistry, Tendon xanthomatosis, ABCA1, biology.protein, ATP-Binding Cassette Transporters, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, ATP Binding Cassette Transporter 1, Lipoprotein
Abstract: We experienced a family with novel massive tendon xanthomatosis which can be excluded from known disease causing xanthomatosis. The proband was a 58-year-old man who had necrosis in his massive Achilles tendon xanthoma. Three of 5 brothers including him and his nephew had the same clinical phenotype. The systemic tendon xanthomatosis became apparent around 30 years of their age. The proband and his elder brother had mild elevations of serum total cholesterol level (251 and 228 mg/dL, respectively). The low-density lipoprotein receptor activity of the proband's lymphocytes was normal. Neither plant sterol nor cholestanol level was increased in the proband's plasma. Magnetic resonance image of the proband's Achilles tendon demonstrated a massive expansion of the soft tissue with salami sausage-like appearance in his heels (50 mm in thickness). The physiological function of macrophages (MPhi) from the patients was investigated to clarify the mechanism for the formation of xanthomatosis. There was no significant difference in the uptake of oxidized low-density lipoprotein between the proband's MPhi and the control. High-density lipoprotein 3-mediated cholesterol efflux from the patients' MPhi (n = 2) was significantly reduced compared with the controls (n = 3), whereas there was no difference in apolipoprotein (apo) A-I-mediated cholesterol efflux between the patients' MPhi and the controls. Furthermore, there was no reduction of the messenger RNA levels of ATP-binding cassette transporter 1 (ABCA1), which is involved in apo A-I-mediated cholesterol efflux, in the proband's MPhi compared with the control. The present study demonstrates that the mechanism for the formation of novel familial massive tendon xanthomatosis may be, at least in part, associated with decreased high-density lipoprotein 3, but not free apo A-I-mediated cholesterol efflux from MPhi in vivo.
Published: 2005

32. Association of Visceral Fat Accumulation and Plasma Adiponectin with Colorectal Adenoma: Evidence for Participation of Insulin Resistance

Author: Takafumi Saito, Sayaka Otake, Hiroaki Takeda, Yuji Matsuzawa, Katsuyoshi Ishihama, Hitoshi Togashi, Yasukuni Suzuki, Tadahisa Fukui, Shinichiro Watanabe, Sumio Kawata, and Tadashi Nakamura
Subjects: Adenoma, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Adipose tissue, Colorectal adenoma, Insulin resistance, Internal medicine, medicine, Homeostasis, Humans, Abdominal obesity, Aged, Adiponectin, business.industry, Insulin, Middle Aged, medicine.disease, Diet, Endocrinology, Adipose Tissue, Oncology, Case-Control Studies, Colorectal Polyp, Body Composition, Intercellular Signaling Peptides and Proteins, Regression Analysis, Female, Insulin Resistance, medicine.symptom, Colorectal Neoplasms, business
Abstract: Purpose: Colorectal carcinogenesis is thought to be related to abdominal obesity and insulin resistance. To investigate whether visceral fat accumulation contributes to colorectal carcinogenesis, we examined its accumulation and the levels of the adipose tissue–derived hormone adiponectin in Japanese patients with colorectal adenoma. Experimental Design: Fifty-one consecutive Japanese patients ages ≥40 years and with colorectal adenoma were subjected to measurement of visceral fat area by computed tomography scanning and plasma adiponectin concentration. The patients also underwent the 75-g oral glucose tolerance test. Insulin resistance was calculated by the homeostasis metabolic assessment (HOMA-IR) method. The controls were 52 Japanese subjects ages ≥40 years and without colorectal polyp. Cigarette smokers and subjects who consumed alcohol (≥30 g ethanol/d) were excluded. Results: The patients with colorectal adenoma showed significantly more visceral fat area and significantly less plasma adiponectin concentration in comparison with the controls [odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.47-3.28; P < 0.001 and OR, 0.24; 95% CI, 0.14-0.41; P < 0.001, respectively] by logistic regression analysis. HOMA-IR index was also associated with colorectal adenoma (OR 2.60; 95% CI, 1.20-5.64; P = 0.040). Visceral fat area and adiponectin were associated with adenoma number (1, 2, ≥ 3), the size of the largest adenoma ( Conclusions: These results suggest an association of visceral fat accumulation and decreased plasma adiponectin concentration with colorectal adenoma in Japanese patients. This study may offer a new insight to understanding the relationship of colorectal carcinogenesis with abdominal obesity and insulin resistance.
Published: 2005

33. Identification of Unique Lipoprotein Subclasses for Visceral Obesity by Component Analysis of Cholesterol Profile in High-Performance Liquid Chromatography

Author: Tadashi Nakamura, Shizuya Yamashita, Masato Ishigami, Yuji Matsuzawa, Naohiko Sakai, Shinichi Usui, and Mitsuyo Okazaki
Subjects: Adult, Male, medicine.medical_specialty, Very low-density lipoprotein, Lipoproteins, Coronary Disease, Lipoproteins, VLDL, Subcutaneous fat, High-performance liquid chromatography, chemistry.chemical_compound, Risk Factors, Internal medicine, medicine, Humans, Obesity, Chromatography, High Pressure Liquid, Aged, Triglyceride, Chemistry, Cholesterol, Middle Aged, medicine.disease, Lipoproteins, LDL, Viscera, Endocrinology, Adipose Tissue, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, Cardiology and Cardiovascular Medicine, Biomarkers, Visceral Obesity, Lipoprotein
Abstract: Objective— The contribution of visceral fat accumulation to the development of coronary heart disease was previously reported, but the relation between visceral fat accumulation and serum lipoprotein subclasses was unknown. Methods and Results— We examined the relation of lipoprotein subclasses with visceral fat accumulation in 62 male subjects (aged 22 to 67 years) with visceral fat syndrome or obesity. Cholesterol levels in very low–density, low-density, and high-density lipoprotein subclasses (VLDL, LDL, and HDL) were determined by computer-assisted high-performance liquid chromatography. Subcutaneous fat area and visceral fat area were measured by computed tomographic scanning. There was no significant correlation between the subcutaneous fat area and the cholesterol levels in all lipoprotein subclasses. In contrast, the visceral fat area was correlated positively ( P P P P Conclusion— These findings indicate that this simple high-performance liquid chromatography method may be applied for easy detection and evaluation of abnormal distribution of lipoprotein subclasses.
Published: 2005

34. Oral Administration of Royal Jelly Facilitates mRNA Expression of Glial Cell Line-Derived Neurotrophic Factor and Neurofilament H in the Hippocampus of the Adult Mouse Brain

Author: Kumiko Ikeno, Tadashi Nakamura, Manabu Hashimoto, Yoshinobu Ogawa, Yoshirou Hayashi, Hidefumi Fukumitsu, Masafumi Kanda, Hiroshi Nomoto, and Shoei Furukawa
Subjects: Male, Aging, DNA, Complementary, Neurofilament, Administration, Oral, Stimulation, Hippocampus, Applied Microbiology and Biotechnology, Biochemistry, Neuroprotection, Analytical Chemistry, Mice, Neurofilament Proteins, Neurotrophic factors, Glial cell line-derived neurotrophic factor, Animals, Glial Cell Line-Derived Neurotrophic Factor, Nerve Growth Factors, RNA, Messenger, Receptor, Molecular Biology, biology, Fatty Acids, Organic Chemistry, General Medicine, Cell biology, Gene Expression Regulation, nervous system, Immunology, biology.protein, GDNF family of ligands, Biotechnology, Neurotrophin
Abstract: Royal jelly (RJ) is known to have a variety of biological activities toward various types of cells and tissues of animal models, but nothing is known about its effect on brain functions. Hence, we examined the effect of oral administration of RJ on the mRNA expression of various neurotrophic factors, their receptors, and neural cell markers in the mouse brain. Our results revealed that RJ selectively facilitates the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that RJ shows neurotrophic effects on the mature brain via stimulation of GDNF production, and that enhanced expression of neurofilament H mRNA is involved in events subsequently caused by GDNF. RJ may play neurotrophic and/or neuroprotective roles in the adult brain through GDNF.
Published: 2005

35. Efficacy of cyclophosphamide combined with prednisolone in patients with AA amyloidosis secondary to rheumatoid arthritis

Author: Kunihiko Tomoda, Tadashi Nakamura, Yuji Yamamura, Masahiro Shono, Satoshi Baba, and Michishi Tsukano
Subjects: Male, medicine.medical_specialty, Genotype, Prednisolone, Risk Assessment, Severity of Illness Index, Drug Administration Schedule, Statistics, Nonparametric, Arthritis, Rheumatoid, Japan, Rheumatology, AA amyloidosis, Internal medicine, Odds Ratio, Humans, Medicine, Rheumatoid factor, Prospective Studies, Serum amyloid A, Cyclophosphamide, Serum Amyloid A Protein, Aged, Probability, Dose-Response Relationship, Drug, medicine.diagnostic_test, business.industry, Amyloidosis, General Medicine, Middle Aged, medicine.disease, Apolipoproteins, Treatment Outcome, Endocrinology, Rheumatoid arthritis, Erythrocyte sedimentation rate, Drug Therapy, Combination, Female, business, Follow-Up Studies, medicine.drug
Abstract: Secondary amyloid A (AA) amyloidosis is an uncommon yet important complication of rheumatoid arthritis (RA). It is one of the most relentless of the extra-articular features of RA, and suitable treatments have not yet been found. We studied the efficacy of cyclophosphamide (CYC) combined with prednisolone (PSL) in amyloidotic patients who had serum amyloid A (SAA) 1.3 genotype, which is a risk factor for secondary amyloidosis in Japanese RA patients. Fifteen RA patients who were SAA1.3 homo- and heterozygotes with biopsy-confirmed AA amyloidosis were treated with a combination of CYC and PSL. Laboratory variables of C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), serum albumin (Alb), serum creatinine (Cre) and Lansbury’s index were carried out by statistical analysis of changes between before and during the medication. According to the Mann–Whitney rank test, CRP, RF, ESR, Alb and Cre levels improved significantly with the combination treatment (p
Published: 2003

36. Matrix Metalloproteinases as Novel Disease Markers in Takayasu Arteritis

Author: Ayumu Hirata, Yuji Matsuzawa, Shizuya Yamashita, Akifumi Matsuyama, Naohiko Sakai, Tadashi Nakamura, Susumu Kashine, Hisatoyo Hiraoka, and Masato Ishigami
Subjects: Adult, Male, Systemic disease, Pathology, medicine.medical_specialty, Disease, Matrix metalloproteinase, Sensitivity and Specificity, Severity of Illness Index, Predictive Value of Tests, Reference Values, Physiology (medical), medicine, Humans, Aged, Tissue Inhibitor of Metalloproteinase-1, medicine.diagnostic_test, Vascular disease, business.industry, Remission Induction, Anatomical pathology, Middle Aged, medicine.disease, Takayasu Arteritis, Matrix Metalloproteinases, Pathophysiology, Matrix Metalloproteinase 9, Erythrocyte sedimentation rate, Disease Progression, Matrix Metalloproteinase 2, Female, Matrix Metalloproteinase 3, Cardiology and Cardiovascular Medicine, Vasculitis, business, Biomarkers
Abstract: Background—Takayasu arteritis (TA) is a chronic vasculitis that primarily affects large elastic arteries. Monitoring of disease activity is crucial because the disease tends to progress despite treatment with glucocorticoid and/or immunosuppressive agents. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have generally been used as disease activity markers, but these are nonspecific inflammatory markers and lack the sensitivity and specificity to accurately monitor the disease status. Given the histological findings characterized by destruction of elastic fibers, we hypothesized that matrix metalloproteinases (MMPs) could be useful as markers of disease activity in TA.Methods and Results—A consecutive series of 25 patients with TA were enrolled in this study. According to the National Institutes of Health criteria of disease activity, 11 were in an active phase and the remaining 14 were in remission. Circulating levels of MMP-2, MMP-3, and MMP-9 were determined by ELISA in all patients with TA and controls. MMP-2 levels were higher in patients with TA than in controls, but no correlation was found between serum MMP-2 and disease activity score. In contrast, MMP-3 and MMP-9 levels in patients with active disease were higher than in patients in remission and controls, and a positive correlation was demonstrated between circulating levels of MMP-3 or MMP-9 and disease activity score. The high levels of MMP-3 and MMP-9 improved when patients underwent remission.Conclusions—The present results indicate that MMP-2 can be helpful in diagnosing TA and that MMP-3 and MMP-9 can be used as activity markers for TA.
Published: 2003

37. Measurement of fasting serum apoB-48 levels in normolipidemic and hyperlipidemic subjects by ELISA

Author: Yasuhiko Saika, Yuji Matsuzawa, Shizuya Yamashita, Yoshiaki Uchida, Naohiko Sakai, Shinji Kihara, Toshiyuki Hibuse, Tadashi Nakamura, Yoshiaki Tomari, Satoru Ito, Koji Ohashi, and Hisatoyo Hiraoka
Subjects: Adult, Male, medicine.medical_specialty, Apolipoprotein B, Microgram, Enzyme-Linked Immunosorbent Assay, Hyperlipidemias, Biochemistry, chemistry.chemical_compound, Endocrinology, Chylomicron remnant, Internal medicine, medicine, Humans, In patient, Lipoprotein metabolism, Triglycerides, Aged, Apolipoproteins B, biology, Triglyceride, business.industry, nutritional and metabolic diseases, Fasting, Cell Biology, Metabolism, Middle Aged, Postprandial Period, Cholesterol, chemistry, biology.protein, Female, lipids (amino acids, peptides, and proteins), Apolipoprotein B-48, business, Chylomicron
Abstract: The present study was designed to evaluate the metabolism of chylomicron and chylomicron remnants by measuring serum apolipoprotein B-48 (apoB-48) levels in 335 normolipidemic and 253 hyperlipidemic subjects using a novel ELISA system. The distribution of fasting serum apoB-48 levels in normolipidemic subjects varied widely, ranging from 24 microgram/ml (mean, 5.2 +/- 3.8 microgram/ml; median, 3.9 microgram/ml). Serum apoB-48 levels correlated with serum triglyceride (TG) concentrations (r = 0.45, P < 0.001), but not with total cholesterol levels. Serum apoB-48 levels were 7 to 18 times higher in patients with Type I, Type V, and Type III hyperlipidemia, and only slightly higher in patients with Type IIa, Type IIb, and Type IV hyperlipidemia, compared with normolipidemic subjects. The calculated apoB-48/TG ratio was elevated only in patients with dysbetalipoproteinemia (apoE2/2 phenotype). In normolipidemic subjects, oral fat loading resulted in about 2-fold increase in serum apoB-48 levels, with a peak level recorded at 3-4 h postloading, and then returned to the baseline level within 6 h. On the other hand, in patients with dysbetalipoproteinemia, serum apoB-48 levels did not change considerably. Our results indicate that serum apoB-48 is a very useful parameter for evaluating lipoprotein metabolism in exogenous pathways.
Published: 2003

38. Atorvastatin markedly improves type III hyperlipoproteinemia in association with reduction of both exogenous and endogenous apolipoprotein B-containing lipoproteins

Author: Tadashi Nakamura, Yuji Matsuzawa, Shizuya Yamashita, Naohiko Sakai, Ken-ichi Hirano, Masato Ishigami, and Hisatoyo Hiraoka
Subjects: Male, Apolipoprotein B-48, medicine.medical_specialty, Very low-density lipoprotein, Apolipoprotein B, Lipoproteins, Atorvastatin, Phospholipid, chemistry.chemical_compound, Internal medicine, Hyperlipoproteinemia Type III, medicine, Humans, Pyrroles, Triglycerides, Aged, Apolipoproteins B, Triglyceride, biology, Cholesterol, Anticholesteremic Agents, Osmolar Concentration, nutritional and metabolic diseases, Middle Aged, Lipids, Apolipoproteins, Endocrinology, chemistry, Heptanoic Acids, Apolipoprotein B-100, biology.protein, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, Lipoprotein, medicine.drug
Abstract: Remnant lipoproteins are known to promote atherosclerosis especially in patients with type III hyperlipoproteinemia (HLP). In the current study, the effects of atorvastatin were investigated with special reference to the exogenous and endogenous apolipoprotein (apo) B-containing lipoprotein metabolism in type III HLP. Four Japanese male patients with type III HLP associated with homozygous apoE2 were studied. One-month administration of atorvastatin (20 mg once daily), after a 4-week dietary run-in, strikingly reduced serum total cholesterol and triglyceride (TG) levels by 52 (P
Published: 2003

39. End-to-end anastomosis in chronic tracheal stenosis

Author: Hiroya Iwatake, Hachiro Suzuki, Kouichiro Tsutsumi, Izumi Koizuka, Tadashi Nakamura, and Isao Kato
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Recurrent nerve, Adenocarcinoma, Anastomosis, Wounds, Nonpenetrating, Tracheostomy, Blunt, Intubation, Intratracheal, medicine, Humans, Intubation, Thyroid Neoplasms, Thyroid cancer, End to end anastomosis, Aged, business.industry, Anastomosis, Surgical, General Medicine, Middle Aged, respiratory system, medicine.disease, Surgery, Tracheal Stenosis, Trachea, Treatment Outcome, Otorhinolaryngology, Chronic Disease, Recurrent Laryngeal Nerve Injuries, Female, Segmental resection, business
Abstract: Objective: This study assessed the efficacy and safety of end-to-end anastomosis of the trachea following segmental resection in chronic tracheal stenosis. Methods: End-to-end anastomoses of the trachea were performed in 35 patients with chronic tracheal stenosis; 18 patients with tracheal invasion of thyroid cancer and 17 patients with long-term intubation and blunt injuries of the trachea. Results: All operations were successful, except one whose unilateral recurrent nerve had not been identified in the recurrent thyroid cancer invasion with trachea. Conclusion: This operation provides a one-step cure for the stenosed trachea and can be applied to the resection of less than six tracheal segments.
Published: 2003

40. Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein

Author: Hidehiko Kondo, Ken Kishida, Yuji Matsuzawa, Yoshihiro Tochino, Shinji Kihara, Hiroyuki Nagaretani, Hiroshi Kuriyama, Norikazu Maeda, Morihiro Matsuda, Tohru Funahashi, Tadashi Nakamura, Naoki Furuyama, Hitoshi Nishizawa, and Iichiro Shimomura
Subjects: Adult, Male, medicine.medical_specialty, Ovariectomy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biology, Mice, chemistry.chemical_compound, Insulin resistance, Internal medicine, Adipocyte, Adipocytes, Internal Medicine, medicine, Animals, Humans, Insulin, Testosterone, Adiponectin secretion, Pancreatic hormone, Mice, Inbred ICR, Sex Characteristics, Adiponectin, Proteins, nutritional and metabolic diseases, 3T3 Cells, Middle Aged, medicine.disease, Mice, Inbred C57BL, Postmenopause, Endocrinology, chemistry, Androgens, Intercellular Signaling Peptides and Proteins, Female, hormones, hormone substitutes, and hormone antagonists, Hormone
Abstract: Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 ± 11.9 years [mean ± SD]) than in 137 women (53.2 ± 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.
Published: 2002

41. Molecular strategy using cis-element ‘decoy’ of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model

Author: T Asai, H Sakonjo, Tadashi Nakamura, Naotaka Hashiya, Ryuichi Morishita, Toshio Ogihara, Keita Yamasaki, Yasufumi Kaneda, N Tsuboniwa, and Motokuni Aoki
Subjects: Male, Intimal hyperplasia, medicine.medical_treatment, Cell Cycle Proteins, Coronary Disease, Anterior Descending Coronary Artery, Transfection, environment and public health, Coronary Restenosis, In vivo, Angioplasty, Intravascular ultrasound, Genetics, medicine, Animals, Angioplasty, Balloon, Coronary, skin and connective tissue diseases, Molecular Biology, Binding Sites, medicine.diagnostic_test, business.industry, Cell Cycle, Balloon catheter, Genetic Therapy, Haplorhini, medicine.disease, biological factors, E2F Transcription Factors, DNA-Binding Proteins, Oligodeoxyribonucleotides, Models, Animal, Immunology, health occupations, Cancer research, Swine, Miniature, Molecular Medicine, Tunica Intima, business, Decoy, Transcription Factors
Abstract: Transcription factor E2F plays a pivotal role in the transactivation of cell cycle regulatory genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for E2F as 'decoy' cis elements may block the activation of genes mediating the cell cycle, resulting in an effective therapeutic agent for treating intimal hyperplasia. In this study, we tested the feasibility of E2F decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model. An angioplasty catheter was inserted in the left anterior descending coronary artery of pigs to cause vascular injury. Initially, we tested the feasibility of transfection of FITC-labeled E2F decoy ODN using a hydrogel balloon catheter. Fluorescence due to E2F decoy ODN could be detected throughout the medial layer. Therefore, we transfected E2F decoy ODN into the balloon-injured artery using hydrogel catheter. Of importance, intravascular ultrasound (IVUS) and histological evaluation demonstrated that plaque area in the balloon-injured artery was significantly reduced by E2F decoy ODN compared with mismatched decoy ODN at 1 month after a single transfection (P < 0.01). In contrast, luminal and total vessel areas were significantly increased in vessels treated with E2F decoy ODN as compared with mismatched decoy. Endothelial function after angioplasty was not affected by E2F decoy transfection. Finally, we tested the acute toxicity of E2F decoy ODN in monkeys, and no apparent side-effects were detected. Here, we report the successful in vivo transfer of E2F decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery without any apparent side-effects.
Published: 2002

42. Effect of ionotropic glutamate receptor antagonists on Fos-like immunoreactivity in the dorsal horn following transection of the rat sciatic nerve

Author: Toshikazu Nishimori, Ryuji Terayama, Yasushi Ishida, Tadashi Nakamura, Noriko Otahara, and Tetsuya Ikeda
Subjects: Male, Nerve Crush, medicine.medical_treatment, Glutamic Acid, Pain, AMPA receptor, Receptors, N-Methyl-D-Aspartate, Synaptic Transmission, Rats, Sprague-Dawley, Ganglia, Spinal, medicine, Animals, Receptors, AMPA, Molecular Biology, Afferent Pathways, Chemistry, General Neuroscience, fungi, Glutamate receptor, Nociceptors, Peripheral Nervous System Diseases, Anatomy, Nerve injury, Spinal cord, Immunohistochemistry, Sciatic Nerve, Rats, Up-Regulation, Posterior Horn Cells, medicine.anatomical_structure, Receptors, Glutamate, nervous system, NMDA receptor, Neurology (clinical), Sciatic nerve, Axotomy, medicine.symptom, Excitatory Amino Acid Antagonists, Proto-Oncogene Proteins c-fos, Developmental Biology, Ionotropic effect
Abstract: Fos-like immunoreactivity (FLI) was investigated in the lumbar dorsal horn 2 h after transection of the rat sciatic nerve and sham operation. FLI following nerve transection was distributed through the medio-lateral extension of the superficial layer of the dorsal horn, while FLI after sham operation, tissue injury, was restricted to the lateral one-third of this layer. The number of FLI neurons in the lateral one-third was similar in the two operations, indicating that neurons expressing FLI in the medial two-thirds and in the lateral one-third of the superficial layer after nerve transection are derived from nerve injury and tissue injury, respectively. FLI in the lateral one-third, but not the medial two-thirds, after nerve transection was significantly reduced by pretreatment with NMDA and AMPA/KA receptor antagonists, indicating that there is a considerable difference in the contributions of ionotropic glutamate receptors to FLI in this layer induced by nerve injury and tissue injury.
Published: 2002

43. Protective Effect of the HLA-DRB1*13:02 Allele in Japanese Rheumatoid Arthritis Patients

Author: Shouhei Nagaoka, Aya Kawasaki, Kiyoshi Migita, Koichiro Saisho, Hajime Sano, Shoji Sugii, Satoshi Ito, Kota Shimada, Atsushi Hashimoto, Hiroshi Furukawa, Shinichiro Tsunoda, Tadashi Nakamura, Akiko Suda, Shigeto Tohma, Naoyuki Tsuchiya, Shomi Oka, Akiko Komiya, Masao Katayama, and Naoshi Fukui
Subjects: Male, Autoimmunity, Pathogenesis, Major Histocompatibility Complex, Arthritis, Rheumatoid, Epitopes, Gene Frequency, Japan, immune system diseases, Genotype, Genetics of the Immune System, Medicine and Health Sciences, Odds Ratio, Amino Acids, skin and connective tissue diseases, HLA-DRB1, Multidisciplinary, biology, Middle Aged, Rheumatoid arthritis, Medicine, Female, Antibody, Research Article, musculoskeletal diseases, Adult, medicine.medical_specialty, Heterozygote, Science, Immunology, Rheumatoid Arthritis, Autoimmune Diseases, Rheumatology, Asian People, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Allele, Alleles, Autoantibodies, business.industry, Arthritis, Biology and Life Sciences, Odds ratio, medicine.disease, Case-Control Studies, biology.protein, Clinical Immunology, business, HLA-DRB1 Chains
Abstract: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. Certain HLA-DRB1 "shared-epitope" alleles are reported to be positively associated with increased RA susceptibility, whereas some of the other alleles may be negatively associated. However, studies on the latter are rare. Here, we focus on the protective effects of DRB1 alleles in Japanese RA patients in an association study. Relative predispositional effects (RPE) were analyzed by sequential elimination of carriers of each allele with the strongest association. The protective effects of DRB1 alleles were investigated in patients stratified according to whether they possessed anti-citrullinated peptide antibodies (ACPA). The DRB1*13:02 allele was found to be negatively associated with RA (P = 4.59×10(-10), corrected P (Pc) = 1.42×10(-8), odds ratio [OR] 0.42, 95% CI 0.32-0.55, P [RPE] = 1.27×10(-6)); the genotypes DRB1*04:05/*13:02 and *09:01/*13:02 were also negatively associated with RA. The protective effect of *13:02 was also present in ACPA-positive patients (P = 3.95×10(-8), Pc = 1.22×10(-6), OR 0.42, 95%CI 0.31-0.58) whereas *15:02 was negatively associated only with ACPA-negative RA (P = 8.87×10(-5), Pc = 0.0026, OR 0.26, 95%CI 0.12-0.56). Thus, this study identified a negative association of DRB1*13:02 with Japanese RA; our findings support the protective role of DRB1*13:02 in the pathogenesis of ACPA-positive RA.
Published: 2014

44. Fat accumulation and obesity-related cardiovascular risk factors in middle-aged Japanese men and women

Author: Kazuaki Kotani, Miwa Ryo, Katsuto Tokunaga, Yuji Matsuzawa, Shinji Kihara, Tohru Funahashi, Tadashi Nakamura, and Iichiro Shimomura
Subjects: Adult, Male, medicine.medical_specialty, genetic structures, Intra-Abdominal Fat, Population, Subcutaneous Fat, Gastroenterology, Body Mass Index, Impaired glucose tolerance, Diabetes Complications, Asian People, Japan, Weight loss, Risk Factors, Internal medicine, Glucose Intolerance, Internal Medicine, medicine, Body Fat Distribution, Humans, Obesity, education, Aged, Dyslipidemias, Metabolic Syndrome, education.field_of_study, business.industry, General Medicine, Middle Aged, medicine.disease, Endocrinology, Cardiovascular Diseases, Hyperglycemia, Hypertension, Female, medicine.symptom, Metabolic syndrome, business, Body mass index, Dyslipidemia
Abstract: Objective A cluster of multiple risk factors has been noted to constitute the background of cardiovascular disease. The purpose of this study was to evaluate the relationship between the visceral fat area (VFA) or subcutaneous fat area (SFA) and a cluster of obesity-related cardiovascular risk factors, including hyperglycemia, dyslipidemia and elevated blood pressure, in middle-aged Japanese men and women. Methods A total of 571 subjects (m=434; f=137; age: 53 ± 9 years) who underwent health examinations with evaluations of body fat distribution using computed tomography scans and assessments of 75-g oral glucose tolerance tests were enrolled in this study. Results The VFA and SFA were linearly correlated with the number of risk factors in both men and women. The area under the receiver-operating characteristic curve of VFA (m=0.741, f=0.763) was significantly higher than that of SFA (m=0.636, f=0.689) with respect to the clustering of risk factors (one or more). The men exhibited larger VFA values and smaller SFA values than the women in similar body mass index (BMI) categories. Men with a VFA of ≥100 cm(2) irrespective of BMI and women with a VFA of ≥100 cm(2) and a BMI of ≥25 kg/m(2) demonstrated a high prevalence of diabetes mellitus and impaired glucose tolerance. Men and women with a VFA of ≥100 cm(2) irrespective of BMI demonstrated a high prevalence of type IIb dyslipidemia. Conclusion These results suggest that the absolute value of VFA rather than SFA is more closely associated with a cluster of risk factors irrespective of sex and is a good marker for selecting subjects to whom weight reduction should be recommended in order to prevent cardiovascular disease in the general population.
Published: 2014

45. Galectin-12, an Adipose-expressed Galectin-like Molecule Possessing Apoptosis-inducing Activity

Author: Morihiro Matsuda, Barbara C. Hansen, Masahiko Takahashi, Yoshihiro Tochino, Shinji Kihara, Hiroshi Kuriyama, Ken Kishida, Yuji Matsuzawa, Tadashi Nakamura, Yuko Matsukawa, Tohru Funahashi, Kikuko Hotta, Hitoshi Nishizawa, and Noni L. Bodkin
Subjects: Male, Adipose tissue, Apoptosis, Cell Cycle Proteins, Biochemistry, Mice, Lectins, Adipocytes, Tissue Distribution, 3T3 Cells, Transfection, Immunohistochemistry, Recombinant Proteins, Hemagglutinins, COS Cells, Protein Binding, medicine.drug, DNA, Complementary, animal structures, Galectins, Adipose tissue macrophages, Molecular Sequence Data, Biology, Complementary DNA, otorhinolaryngologic diseases, medicine, Animals, Humans, Amino Acid Sequence, RNA, Messenger, Molecular Biology, Gene Library, Galectin, Cell Nucleus, Base Sequence, Sequence Homology, Amino Acid, cDNA library, Troglitazone, Galactosides, Cell Biology, Blotting, Northern, Macaca mulatta, Molecular biology, Protein Structure, Tertiary, Rats, Rats, Zucker, Mice, Inbred C57BL, Thiazoles, stomatognathic diseases, Protein Biosynthesis, Thiazolidinediones
Abstract: Galectins constitute a family of proteins that bind to beta-galactoside residues and have diverse physiological functions. Here we report on the identification of a galectin-like molecule, galectin-12, in a human adipose tissue cDNA library. The protein contained two potential carbohydrate-recognition domains with the second carbohydrate-recognition domain being less conserved compared with other galectins. In vitro translated galectin-12 bound to a lactosyl-agarose column far less efficiently than galectin-8. Galectin-12 mRNA was predominantly expressed in adipose tissue of human and mouse and in differentiated 3T3-L1 adipocytes. Caloric restriction and treatment of obese animals with troglitazone increased galectin-12 mRNA levels and decreased the average size of the cells in adipose tissue. The induction of galectin-12 expression by the thiazolidinedione, troglitazone, was paralleled by an increase in the number of apoptotic cells in adipose tissue. Immunocytochemical analysis revealed that galectin-12 was localized in the nucleus of adipocytes, and transfection with galectin-12 cDNA induced apoptosis of COS-1 cells. These results suggest that galectin-12, an adipose-expressed galectin-like molecule, may participate in the apoptosis of adipocytes.
Published: 2001

46. The Expression of SPARC in Adipose Tissue and Its Increased Plasma Concentration in Patients with Coronary Artery Disease

Author: Hiroshi Kuriyama, Kikuko Hotta, Ken Kishida, Yuji Matsuzawa, Hitoshi Nishizawa, Shizuya Yamashita, Tohru Funahashi, Iichiro Shimomura, Noriyuki Ouchi, Kazuhisa Maeda, Masahiko Takahashi, Norikazu Maeda, Hiroyuki Nagaretani, Tadashi Nakamura, and Shinji Kihara
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Gene Expression, Medicine (miscellaneous), Adipose tissue, Coronary Disease, Body Mass Index, Immunoenzyme Techniques, Coronary artery disease, Mice, chemistry.chemical_compound, Endocrinology, In vivo, Internal medicine, Adipocyte, RNA, Ribosomal, 28S, Gene expression, Animals, Humans, Medicine, Osteonectin, Obesity, RNA, Messenger, Northern blot, biology, business.industry, Public Health, Environmental and Occupational Health, Middle Aged, Blotting, Northern, medicine.disease, Up-Regulation, Mice, Inbred C57BL, Blot, Adipose Tissue, chemistry, biology.protein, Female, business, Food Science
Abstract: Objective: Adipocytes secrete various cytokines and matrix proteins. Several of them precipitate in obesity-associated diseases, including atherosclerosis. In the current study, we have examined the expression of secreted protein, acidic and rich in cysteine (SPARC) in adipose tissue and its significance in obesity and coronary artery disease (CAD). Research Methods and Procedures: The SPARC mRNA expressions both in vivo and in vitro were detected by Northern blot analysis. Plasma SPARC concentrations were measured by enzyme immunosorbent assay. First, we investigated the plasma SPARC levels of 88 unrelated adult Japanese subjects (62 men and 26 women; average age: [± SD] 50 ± 12 years; body mass index [BMI]: 16 to 46 kg/m2). Additionally 31 subjects with CAD diagnosed by coronary angiography (20 men and 11 women) were also investigated. Results: Human adipose tissues expressed abundant SPARC mRNA. SPARC expression in adipose tissues was upregulated in obese db/db mice. Markedly enhanced expression of SPARC mRNA was observed in 3T3-L1 fibroblasts during adipocyte differentiation. Consistent with these results, plasma SPARC levels proved a positive correlation with BMI in humans (r = 0.27; p < 0.01). Interestingly, plasma SPARC concentrations were significantly elevated in age- and BMI-matched subjects with CAD (p < 0.05). Discussion: SPARC was expressed in adipose tissues and its expression was enhanced in obese mice. In human, plasma SPARC levels were elevated in obesity and CAD patients. This elevated SPARC may be involved in the progression of CAD.
Published: 2001

47. Effects of previous noxious stimulus applied to remote areas on noxious stimulus-evoked c-Fos expression in the rat trigeminal nucleus caudalis

Author: Ryuji Terayama, Tetsuya Ikeda, Tadashi Nakamura, Mikako Koganemaru, Nahoko Nagamatsu, and Toshikazu Nishimori
Subjects: Male, Dorsum, animal structures, c-Fos, Rats, Sprague-Dawley, Fixatives, Trigeminal Caudal Nucleus, Formaldehyde, Forelimb, Noxious stimulus, medicine, Animals, Trigeminal system, Neurons, biology, Chemistry, General Neuroscience, Diffuse noxious inhibitory control, General Medicine, Anatomy, Trigeminal nucleus, Stimulation, Chemical, Rats, medicine.anatomical_structure, Vibrissae, biology.protein, Proto-Oncogene Proteins c-fos, Neuroscience, Nucleus
Abstract: Noxious stimulus-evoked c-Fos expression in the spinal dorsal horn is modulated by noxious stimuli applied previously to remote areas of the body. To confirm the existence of such modulation in c-Fos expression in the trigeminal system, changes in c-Fos expression in the trigeminal nucleus caudalis induced by formalin injection into the rat whisker pad were examined by previously injecting formalin into different areas (contralateral whisker pad, ipsilateral or contralateral forepaw) of the body. Formalin injection-evoked c-Fos expression in this nucleus was significantly reduced by previous formalin injection into the contralateral whisker pad or ipsilateral forepaw but not into the contralateral forepaw. The interval between the two injections of formalin that produced a maximal reduction of formalin injection-evoked c-Fos expression was 1 h, and the reduction of c-Fos expression was less when the interval of the two noxious stimuli was longer or shorter than 1 h. These results suggested that noxious stimulus-evoked c-Fos expression in the trigeminal nucleus caudalis is reduced by noxious stimulus applied previously to remote areas, and the reduction is dependent on the area of previous noxious stimulation and interval between the two noxious stimuli.
Published: 2001

48. Plasma Concentrations of a Novel, Adipose-Specific Protein, Adiponectin, in Type 2 Diabetic Patients

Author: Tadashi Nakamura, Tohru Funahashi, Yasukazu Ohmoto, Yukio Arita, Makoto Nishida, Toshiaki Hanafusa, Tadahisa Nakajima, Masahiko Takahashi, Noriyuki Ouchi, Yuji Matsuzawa, Yoshihisa Okamoto, Kazuhisa Maeda, Hiroshi Kuriyama, Naohiko Sakai, Shizuya Yamashita, Kyoichi Hasegawa, Hiromi Iwahashi, Kikuko Hotta, Masahiro Muraguchi, Shinji Kihara, and Morihiro Matsuda
Subjects: Adult, Blood Glucose, Leptin, Male, medicine.medical_specialty, Coronary Disease, Body Mass Index, chemistry.chemical_compound, Diabetes mellitus, Internal medicine, Humans, Insulin, Medicine, Adiponectin secretion, Triglycerides, Adiponectin receptor 1, Adiponectin receptor 2, Adiponectin, business.industry, Microangiopathy, Proteins, Fasting, Middle Aged, medicine.disease, AdipoRon, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Intercellular Signaling Peptides and Proteins, Female, Cardiology and Cardiovascular Medicine, business, Diabetic Angiopathies
Abstract: Abstract —Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)–matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6±0.4 versus 7.9±0.5 μg/mL in men, 7.6±0.7 versus 11.7±1.0 μg/mL in women; P P r =−0.18, P r =−0.26, P
Published: 2000

49. An Adipocyte-Derived Plasma Protein, Adiponectin, Adheres to Injured Vascular Walls

Author: Makoto Nishida, Yukio Arita, Masahiko Takahashi, Yoshihisa Okamoto, Masahiro Muraguchi, Noriyuki Ouchi, Takumi Igura, Yoshiaki Inui, Tohru Funahashi, Shizuya Yamashita, Yuji Matsuzawa, S. Kihara, Jun-ichiro Miyagawa, and Tadashi Nakamura
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Complement factor I, In Vitro Techniques, Transfection, Biochemistry, Iodine Radioisotopes, Rats, Sprague-Dawley, Gene product, chemistry.chemical_compound, Endocrinology, Adipocyte, Internal medicine, Complementary DNA, Adipocytes, medicine, Animals, Extracellular Matrix Proteins, COS cells, Adiponectin, Chemistry, Biochemistry (medical), Proteins, Blood Proteins, General Medicine, Rats, Adipose Tissue, COS Cells, Intercellular Signaling Peptides and Proteins, Collagen, Endothelium, Vascular, Carotid Artery Injuries, Angioplasty, Balloon, hormones, hormone substitutes, and hormone antagonists, Protein Binding
Abstract: Adipose tissue secretes a variety of proteins into the bloodstream. We have previously reported a novel cDNA, apM1 (adipose most abundant gene transcript 1), which is specifically and abundantly expressed in adipose tissue [1]. Primary structure analysis predicted that the apM1 gene product possesses significant homology to collagens VIII, X and complement factor C1q, and we named it adiponectin. In the current study, we analyzed characteristics of adiponectin in vitro and in vivo. Adiponectin protein was proved to be secreted into the medium when the cDNA was transfected to COS cells. Anti-adiponectin cross-reactivities were abundantly detected in the human plasma. In solid-phase binding assays, adiponectin specifically bound to collagen types I, III and V, which are present in vascular intima. Immunohistochemical analysis revealed that adiponectin was detected in the walls of the catheter-injured vessels but not in the intact vascular walls. These data suggest that adiponectin is a plasma protein produced by adipose tissue and accumulates in vascular walls when the endothelial barrier is injured.
Published: 2000

50. Abdominal Fat: Standardized Technique for Measurement at CT

Author: Kouichi Yamasaki, Abdul Hasan M. Waliul Islam, Tohru Funahashi, Tohru Yoshizumi, Kazuaki Kotani, Mitsukazu Yamane, Tadashi Nakamura, Yuji Matsuzawa, Masakazu Menju, Shizuya Yamashita, and Takeshi Arai
Subjects: Adult, Male, medicine.medical_specialty, Computed tomography, Standardized technique, Hounsfield scale, Abdominal fat, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Obesity, Observer Variation, Measurement method, medicine.diagnostic_test, business.industry, Attenuation, Reproducibility of Results, Middle Aged, medicine.anatomical_structure, Adipose Tissue, Case-Control Studies, Body Constitution, Abdomen, Female, Radiology, Tomography, Tomography, X-Ray Computed, business, Nuclear medicine
Abstract: The authors estimated abdominal fat distribution on the basis of measurements at computed tomography (CT). The attenuation range for fat tissue was defined as the interval within the mean plus or minus 2 SDs considered to be individual variation. Fat areas found with this method were closely correlated with those obtained by means of the computed planimetric method or with a fixed attenuation range from -190 to -30 HU as the standard of reference. Although the average CT numbers obtained with different scanners were distributed widely, the calculated fat areas were almost identical. This method might be a practical and standardized method at CT.
Published: 1999

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