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103. Expression and activation of mitogen-activated protein kinase in the human endometrium during the menstrual cycle

Author

Miyazaki, Kohji, Kanasaki, Haruhiko, and Takahashi, Kentaro

Subjects
Protein kinases -- Health aspects, Menstrual cycle -- Health aspects, Endometrium -- Analysis, Health
Abstract

The fluctuation of expression and activation of mitogen-activated protein kinase in normal human endometrium throughout the menstrual cycle is investigated. The expression and fluctuation of extracellular signal-regulated kinase in the human endometrium is increased during the secretory phase, suggesting that fluctuation of extracellular signal-regulated kinase in the human endometrium might be induced by ovarian steroid hormones.

Published
2006

105. “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin

Author

Pavlidis, Stelios, Takahashi, Kentaro, Kwong, Francois Ng Kee, Xie, Jiaxing, Hoda, Uruj, Sun, Kai, Elyasigomari, Vahid, Agapow, Paul, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Shaw, Dominic E., Fleming, Louise J., Howarth, Peter H., Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Knowles, Richard, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Djukanovic, Ratko, Chung, Kian Fan, Pavlidis, Stelios, Takahashi, Kentaro, Kwong, Francois Ng Kee, Xie, Jiaxing, Hoda, Uruj, Sun, Kai, Elyasigomari, Vahid, Agapow, Paul, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Shaw, Dominic E., Fleming, Louise J., Howarth, Peter H., Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Knowles, Richard, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Djukanovic, Ratko, and Chung, Kian Fan

Abstract

Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild–moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort. The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs. 37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild–moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (30 ppb) and blood eosinophils (300 cells·µL −1 ) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression. T2-high severe asthma can be predicted to some extent from raised levels of FeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high. Copyright ©ERS 2019.

Published
2019

108. Research Paper: Comparison of Embryo Development and Pregnancy Rates in Continuous Single and Sequential Media Cultures of Sibling Embryos

Author

Takashima, Akiko, primary, Kimura, Fuminori, additional, Kishida, Kazumi, additional, Izuno, Mika, additional, Hirata, Kimiko, additional, Takebayashi, Akie, additional, Amano, Tsukuru, additional, Tsuji, Shunichiro, additional, Kaku, Shoji, additional, Onoa, Tesuo, additional, Takahashi, Kentaro, additional, and Murakmai, Takashi, additional

Published
2019
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117. Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED : an exploratory analysis

Author

Takahashi, Kentaro, Pavlidis, Stelios, Kwong, Francois Ng Kee, Hoda, Uruj, Rossios, Christos, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandström, Thomas, Shaw, Dominic E., Lutter, Rene, Bakke, Per, Fleming, Louise J., Howarth, Peter H., Caruso, Massimo, Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Chung, Kian Fan, Takahashi, Kentaro, Pavlidis, Stelios, Kwong, Francois Ng Kee, Hoda, Uruj, Rossios, Christos, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandström, Thomas, Shaw, Dominic E., Lutter, Rene, Bakke, Per, Fleming, Louise J., Howarth, Peter H., Caruso, Massimo, Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J., Guo, Yike, Adcock, Ian M., and Chung, Kian Fan

Abstract

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed. Colony-stimulating factor (CSF) 2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated. Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

Published
2018
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118. Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: An exploratory analysis

Author

U-BIOPRED study group, Takahashi, Kentaro, Guo, Yike, Chung, Kian Fan, U-BIOPRED study group, Takahashi, Kentaro, Guo, Yike, and Chung, Kian Fan

Abstract

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed. Colony-stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated. Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

Published
2018

120. The Joint Crediting Mechanism (JCM) at a glance

Author

Mizuno, Yuji, Takahashi, Kentaro, Rocamora, Alexis, and ロカモラ, アレクシ R.

Subjects
Market Mechanisms
Abstract

The Article 6 of the Paris Agreement lays the groundwork for the operation of carbon market after 2020 by providing room for top-down and bottom-up approaches. Linkages between these mechanisms should be promoted to fully enable the potential of market mechanism to contribute to climate mitigation. Although the accounting method toward Nationally Determined Contributions (NDCs) remains to be established, the Joint Crediting Mechanism (JCM) partner countries have recognised that JCM credits can be used as part of their own NDC’s pledge for mitigation efforts, while avoiding double counting, ensuring transparency and environmental integrity. This discussion paper summarizes the current status of the JCM for further understanding on its implementation.

Published
2017

121. Photoluminescence and scintillation properties of Ce-doped CaBr2 crystals.

Author

Takahashi, Kentaro, Kimura, Hiromi, Nakauchi, Daisuke, Kato, Takumi, Kawaguchi, Noriaki, and Yanagida, Takayuki

Abstract

Ce-doped CaBr2 crystals were evaluated for photoluminescence (PL) and scintillation properties. The samples showed PL peaking at 370 and 400 nm and decay time constants of 22 ns, which were due to 5d–4f transitions of Ce3+ ions. The PL maximum quantum yield was 66.1% in the 1% Ce-doped sample upon excitation at 340 nm. Under X-ray irradiation, the samples showed an emission peak at 400 nm due to the 5d–4f transitions of Ce3+ ions. The 0.1% Ce-doped sample showed intrinsic emission at around 590 nm as well. From the scintillation decay curves, the two components with decay time constants of ∼20 and 200–400 ns were obtained. Their origins would be attributed to the 5d–4f transitions of Ce3+ ions and intrinsic emission, respectively. From the pulse height spectra, the light yield of the 0.1% Ce-doped sample was 50 ph/5.5 MeV-α. [ABSTRACT FROM AUTHOR]

Published
2020
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123. “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin

Author

Pavlidis, Stelios, primary, Takahashi, Kentaro, additional, Ng Kee Kwong, Francois, additional, Xie, Jiaxing, additional, Hoda, Uruj, additional, Sun, Kai, additional, Elyasigomari, Vahid, additional, Agapow, Paul, additional, Loza, Matthew, additional, Baribaud, Fred, additional, Chanez, Pascal, additional, Fowler, Steve J., additional, Shaw, Dominic E., additional, Fleming, Louise J., additional, Howarth, Peter H., additional, Sousa, Ana R., additional, Corfield, Julie, additional, Auffray, Charles, additional, De Meulder, Bertrand, additional, Knowles, Richard, additional, Sterk, Peter J., additional, Guo, Yike, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, and Fan Chung, Kian, additional

Published
2018
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124. Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis

Author

Takahashi, Kentaro, primary, Pavlidis, Stelios, additional, Ng Kee Kwong, Francois, additional, Hoda, Uruj, additional, Rossios, Christos, additional, Sun, Kai, additional, Loza, Matthew, additional, Baribaud, Fred, additional, Chanez, Pascal, additional, Fowler, Steve J., additional, Horvath, Ildiko, additional, Montuschi, Paolo, additional, Singer, Florian, additional, Musial, Jacek, additional, Dahlen, Barbro, additional, Dahlen, Sven-Eric, additional, Krug, Norbert, additional, Sandstrom, Thomas, additional, Shaw, Dominic E., additional, Lutter, Rene, additional, Bakke, Per, additional, Fleming, Louise J., additional, Howarth, Peter H., additional, Caruso, Massimo, additional, Sousa, Ana R., additional, Corfield, Julie, additional, Auffray, Charles, additional, De Meulder, Bertrand, additional, Lefaudeux, Diane, additional, Djukanovic, Ratko, additional, Sterk, Peter J., additional, Guo, Yike, additional, Adcock, Ian M., additional, and Chung, Kian Fan, additional

Published
2018
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129. Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation

Author

Natsume, Yu, primary, Oaku, Kasumi, additional, Takahashi, Kentaro, additional, Nakamura, Wakana, additional, Oono, Ai, additional, Hamada, Satomi, additional, Yamazoe, Masahiro, additional, Ihara, Kensuke, additional, Sasaki, Takeshi, additional, Goya, Masahiko, additional, Hirao, Kenzo, additional, Furukawa, Tetsushi, additional, and Sasano, Tetsuo, additional

Published
2018
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134. Fetal Right Ventricular Diverticulum Detected by Prenatal Ultrasound Screening

Author

Katsura, Daisuke, Hayashi, Kaori, Tsuji, Shunichiro, Ono, Tetsuo, Ishiko, Akiko, Takahashi, Kentaro, and Murakami, Takashi

Subjects
Article Subject, cardiovascular system, cardiovascular diseases
Abstract

Prenatal ultrasound screening has allowed for the detection of in utero cardiac abnormalities. Specifically, distinction is possible between ventricular diverticula and aneurysms, which is important because each condition has a different clinical outcome. We report the case of a 35-year-old, gravida 1, para 1 woman, with no significant past medical history, who underwent routine prenatal ultrasound screening at 32 weeks’ gestation. A four-chamber ultrasound of the fetal heart combined with M-mode echocardiography showed abnormal dilatation of the right ventricular chamber measuring 2.2 cm × 1.0 cm but with normal contractility. Delivery was performed at full term by cesarean section, and a right ventricular diverticulum was confirmed by postnatal cardiac computed tomography. The baby developed normally with no cardiac sequelae during followup. This case demonstrates the importance of making a correct diagnosis of ventricular diverticula by prenatal ultrasound when abnormal dilatation of the fetal ventricle is identified during routine screening. Because evaluating the wall contractility by M-mode ultrasound leads to evaluating whether it has the myocardium, we conclude that M-mode echocardiography is effective for the purpose of prenatal cardiac diagnosis and can distinguish between ventricular aneurysms and functioning ventricular diverticula.

Published
2016
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140. Exploring influential factors on transition process of vehicle ownership in developing Asian city, A case study in Bogor city Indonesia

Author

Nugroho, Sudarmanto Budi, primary, Zusman, Eric, additional, Nakano, Ryoko, additional, Takahashi, Kentaro, additional, Kaswanto, Regan Leonardus, additional, Arifin, Hadi Susilo, additional, Arifin, Nurhayati, additional, Munandar, Aris, additional, Muchtar, Mochamad, additional, Gomi, Kei, additional, and Fujita, Tsuyoshi, additional

Published
2017
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142. Selective degradation of splicing factor CAPERα by anticancer sulfonamides

Author

Uehara, Taisuke, primary, Minoshima, Yukinori, additional, Sagane, Koji, additional, Sugi, Naoko Hata, additional, Mitsuhashi, Kaoru Ogawa, additional, Yamamoto, Noboru, additional, Kamiyama, Hiroshi, additional, Takahashi, Kentaro, additional, Kotake, Yoshihiko, additional, Uesugi, Mai, additional, Yokoi, Akira, additional, Inoue, Atsushi, additional, Yoshida, Taku, additional, Mabuchi, Miyuki, additional, Tanaka, Akito, additional, and Owa, Takashi, additional

Published
2017
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144. Effects of β-estradiol on cold-sensitive receptor channel TRPM8 in ovariectomized rats

Author

Kubo, Takuro, primary, Tsuji, Shunichiro, additional, Amano, Tsukuru, additional, Yoshino, Fumi, additional, Niwa, Yoko, additional, Kasahara, Kyoko, additional, Yoshida, Saori, additional, Mukaisho, Ken-ichi, additional, Sugihara, Hiroyuki, additional, Tanaka, Sachiko, additional, Kimura, Fuminori, additional, Takahashi, Kentaro, additional, and Murakami, Takashi, additional

Published
2017
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148. Effects of high-dose dexamethasone in postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.

Author

Takahashi, Akimasa, Kita, Nobuyuki, Tanaka, Yuji, Tsuji, Shunichiro, One, Tetsuo, Ishiko, Akiko, Kimura, Fuminori, Takahashi, Kentaro, and Murakami, Takashi

Subjects
HELLP syndrome, LIVER enzymes, PUERPERAL disorders, ASPARTATE aminotransferase, DEXAMETHASONE, MEDICAL sciences, ADRENOCORTICAL hormones, ALANINE aminotransferase
Abstract

This study was performed to investigate the effectiveness of dexamethasone in the management of postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. This retrospective study was conducted on 18 women with class 1 HELLP syndrome at the Shiga University of Medical Science. They were divided into two groups: Group A comprised participants who did not receive dexamethasone, and Group B comprised participants that intravenously received dexamethasone. The main outcomes were the serum laboratory values, mortality and morbidity. The only significant difference between the two groups in baseline characteristics was the aspartate aminotransferase levels. The linear regression analysis showed a significant difference between the two groups in the recovery of platelet counts (p = .046) and aspartate aminotransferase (p = .009). These findings support the use of high-dose dexamethasone to promote recovery of the platelet counts and aspartate aminotransferase levels in postpartum women with class 1 HELLP syndrome. Impact statement What is already known on this subject? Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is one of the most dangerous complications that can occur during pregnancy and is considered a particularly serious variant of severe preeclampsia. Several clinical trials have been performed since 1994 because it was expected that corticosteroid therapy, primarily with dexamethasone, accelerates recovery after delivery. However, the effect of dexamethasone therapy on class 1 HELLP syndrome is unclear. What do the results of this study add? In this retrospective study, we demonstrated that dexamethasone administration significantly improved the recovery of the platelet count in postpartum women with class 1 HELLP syndrome, and did not increase the rate of maternal postpartum complications. What are the implications of these findings for clinical practice and/or further research? The use of high-dose dexamethasone in postpartum women with class 1 HELLP syndrome might be effective to promote recovery of the platelet count, and contributes a shorter duration of hospitalisation. Because the number of patients with class 1 HELLP syndrome is small, it is important to confirm these findings with well-designed multicentre prospective studies. [ABSTRACT FROM AUTHOR]

Published
2019
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149. Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics.

Author

Takahashi, Kentaro, Meguro, Kazuyuki, Kawashima, Hirotoshi, Kashiwakuma, Daisuke, Kagami, Shin-ichiro, Ohta, Shoichiro, Ono, Junya, Izuhara, Kenji, and Iwamoto, Itsuo

Subjects
*ASTHMATICS, *PERIOSTIN, *SERUM, *FLUTICASONE propionate, *INFLAMMATION
Abstract

Objective: Periostin, a matricellular protein, is produced from airway epithelial cells and lung fibroblasts by IL-13. It has been suggested that periostin is involved in allergic inflammation and fibrosis. However, the usefulness of serum periostin measurement in the assessment of airway inflammation and remodeling and management of asthmatic patients is still debated. We aimed to determine whether serum periostin levels reflect eosinophilic airway inflammation and airway remodeling in asthma. Methods: We examined the relationship of serum periostin levels with clinical features, biomarkers for eosinophilic airway inflammation, fraction of exhaled nitric oxide (FeNO) levels and blood eosinophil counts, and pulmonary functions in 235 well-controlled asthmatic patients on inhaled corticosteroids (ICS) treatment. Results: Serum periostin levels were positively correlated with blood eosinophil counts (%) and age (r = 0.36 and 0.23, respectively), and were negatively correlated with body weight and FEV1/FVC (%) (r = −0.24 and − 0.23, respectively) in well-controlled asthmatic patients on ICS treatment (daily dose of 453 µg equivalent to fluticasone propionate). Blood eosinophil counts and serum periostin levels were similarly associated with increased FeNO levels (≥40 ppb) in the asthmatics. Serum periostin levels were better associated with fixed airflow limitation (FEV1/FVC ratio <70%) than FeNO levels, blood eosinophil counts or total IgE levels in the asthmatics. Multivariate analysis showed that fixed airflow limitation was significantly associated with high serum periostin levels (≥97 ng/ml) (Odds ratio 3.2). Conclusions: Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics on ICS treatment. [ABSTRACT FROM AUTHOR]

Published
2019
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150. Genetic analysis and phenotype in von Hippel-Lindau disease

Author

Takahashi, Kentaro and Iida, Keiji

Subjects
肝血管腫, 褐色細胞腫, 家族性腫瘍, von Hippel-Lindau病, 遺伝子解析
Abstract

von Hippel-Lindau (VHL)病は血管芽腫,腎透明細胞癌,褐色細胞腫,膵腫瘍,精巣上体嚢胞腫,などの腫瘍が多発する常染色体優性遺伝の家族性腫瘍症候群であり,VHL遺伝子がその原因遺伝子とされている。今回我々は,当科においてVHL病が疑われる4家系22名の患者に対し遺伝子解析を行なった。VHL遺伝子のβsheet領域のナンセンス変異の症例では褐色細胞腫を伴わないVHL病タイプ1の表現型を示し,α domainのミスセンス変異の家系では褐色細胞腫を伴うVHLタイプ2であり,既報の所見を確認できた。また,新規変異を同定した家系1では,褐色細胞腫に加えて肝血管腫の合併を見出した。最近VHL遺伝子のノックアウトマウスで高率に肝血管腫を発症することが報告された。今までヒトのVHL病で肝血管腫合併の報告は乏しいが,今回合併例が見出されたことより,VHL遺伝子変異の種類と肝血管腫合併の関連について注意深く観察し分析することは病態のメカニズム解明に重要であると思われる。, Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome, characterized by retinal, spinal, and cerebellar haemangioblastomas, clear cell renal carcinomas, phaeochromocytomas, pancreatic tumors, and endolymphatic sac tumor that is associated with a germ line mutation of the VHL gene. We performed genetic analysis in patients with VHL disease and their family members, and identified 4 different mutations of the VHL gene. As described previously, patients with nonsense mutation at the region encoding the β sheet showed type 1 VHL disease without pheochromocytoma (PHE) whereas those with missense mutation at the region encoding the α domain showed type 2 phenotype with PHE. In addition, we identified a novel missense mutation (P154S) in family 1. It is of interest that one of the family members showed hepatic hemangiomas (HH) as well as PHE. Although HH is not reported as a phenotype of VHL disease so far, heterozygous vhl gene disrupted mice (vhl+/-mice) demonstrated HH, suggesting that HH may be one the phenotype of VHL disease even in human. Codon 154 is located at the boundary between α and β domain of the VHL protein. In summary, the finding in our patients suggests that HH may be one of the phenotype of human VHL disease and may provide novel information about genotype-phenotype correlation in terms of hepatic hemangioma in human VHL disease.

Published
2005

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