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Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 10/2013 (807-815)

Difference between the frequencies of antisecretory drug prescriptions in users of buffered vs. enteric-coated low-dose aspirin therapies

Hiroko Hachiken¹, Ai Murai¹, Kyoichi Wada², Takeshi Kuwahara², Kouichi Hosomi¹ and Mitsutaka Takada¹

¹Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, and ²Department of Pharmacy, National Cerebral and Cardiovascular Center, Osaka, Japan
Objective: To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. Methods: Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. Results: In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 – 3.03) and 1.87 (95% CI, 1.26 – 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). Conclusions: Our findings do not support the notion that entericcoated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kinki University
577-8502, 3-4-1, Kowakae,
Higashi-osaka, Osaka, 577-8502, Japan
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 10/2016 (795-803)

Long-term impact of therapeutic drug monitoring on the risk of hypoglycemia in HOCM patients on cibenzoline therapy 

Yutaro Mukai¹,², Kyoichi Wada¹,², Mai Fujimoto³, Kouichi Hosomi³, Takeshi Kuwahara¹,², Mitsutaka Takada²,³

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Osaka, ²Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, and ³Division of Clinical Drug Informatics, Kindai University School of Pharmacy, Higashi-osaka, Japan
Objective: The purpose of this study was to evaluate the long-term impact of therapeutic drug monitoring (TDM) services on the risk of hypoglycemia in cibenzoline therapy. In addition, we evaluated the impact of changes in clinical setting or patient background on the risk of hypoglycemia in patients receiving cibenzoline. Methods: TDM services for cibenzoline have been performed at the Japan National Cerebral and Cardiovascular Center since March 1998. A case-control study was performed from September 2012 to February 2013, and the calculated risk of hypoglycemia associated with cibenzoline use was compared with data from our previous studies, which were performed ~ 15 years ago. Results: A significantly increased risk for hypoglycemia was observed for users of cibenzoline (adjusted OR: 2.6; 95% CI: 1.5 – 4.7). In an additional analysis, the calculated risk was slightly reduced (adjusted OR; 2.1, 95% CI; 1.1 – 3.8) and hypertrophic obstructive cardiomyopathy (HOCM) was identified as a possible risk factor for hypoglycemia (adjusted OR: 4.7, 95% CI: 1.8 – 12.3). There was a significant difference in the mean level of cibenzoline between outpatients with and without HOCM (360.5 ± 166.9 ng/mL vs. 276.4 ± 136.3 ng/mL). An inverse relationship was observed between the percentage of outpatients whose cibenzoline serum level had been measured and their risk of hypoglycemia. Conclusions: Consistent TDM services for cibenzoline have contributed to a reduced risk of hypoglycemia associated with cibenzoline therapy. Patients with HOCM have a higher risk of developing hypoglycemia. Clinicians should therefore carefully monitor serum glucose levels in patients with HOCM taking cibenzoline. Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University School of Pharmacy
577-8502, 3-4-1, Kowakae, Higashi-osaka,
Osaka, 577-8502, Japan
Email: takada@ phar.kindai.ac.jp

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 1/2017 (1-8)

Circadian pharmacokinetics and limited sampling strategy of everolimus in heart transplant patients 

Yuka Terada¹#²#³, Kyoichi Wada¹#³, Sachi Matsuda¹, Takeshi Kuwahara¹#³, Atsufumi Kawabata², Mitsutaka Takada³, Takuya Watanabe⁴, Seiko Nakajima⁴, Takuma Sato⁴, Osamu Seguchi⁴, Masanobu Yanase⁴, Norihide Fukushima⁴, Takeshi Nakatani⁴ 

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ²Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, ³Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, and ⁴Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Objective: To evaluate circadian changes in everolimus (EVL) pharmacokinetics and to identify the time point of blood sampling with the strongest correlation with the area under the blood concentration-time curve (AUC) of EVL in heart transplant patients. Methods: Heart transplant patients receiving the same dose of EVL twice a day were reviewed. In 28 patients enrolled, whole blood samples were collected before (C₀), and 1, 2, 4, 6, 8, and 12 hours after each administration of EVL. Blood concentrations of EVL were compared between active (9:00 AM to 9:00 PM) and resting periods (9:00 PM to 9:00 AM). Results: AUC_0–4h, peak concentration (C_max), C_max/minimum concentration, and peak-trough fluctuation in the resting period were significantly lower than those in the active period (p = 0.008, 0.017, 0.022, and 0.011, respectively). Half-life and mean residence time were significantly longer in the resting period than in the active period (p = 0.002 and 0.002, respectively). AUC_0–12h in the active period was similar (p = 0.154) and correlated with that in the resting period (r² = 0.93). Two-point blood samplings, C₀ and C₂, correlated more strongly with AUC_0–12h for EVL, compared with C₀ alone (0.92 vs. 0.79, respectively, for r² in the active period). Conclusions: EVL pharmacokinetics showed circadian changes, suggesting delayed absorption and decreased metabolic activity at rest. However, the circadian changes did not affect AUC_0–12h. A 2-time-point model that included C₀ and C₂ was more accurate for predicting the AUC_0–12h of EVL than C₀ alone in heart transplant patients. Correspondence to:
Kyoichi Wada, PhD 
Department of  Pharmacy
National Cerebral and Cardiovascular Center
5-7-1 Fujishirodai, Suita 565-8565, Japan 
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 56 – No. 4/2018 (184-188)

Use of rifabutin to treat tuberculosis in a cardiac transplant recipient: A case report 

Maya Takayoshi¹, Kyoichi Wada¹#², Yuka Terada¹, Sachi Matsuda¹, Kazuki Nakagita¹#², Akira Oita¹, Mitsutaka Takada², Aki Shionoiri³, Haruki Sunami³, Seiko Nakajima³, Kensuke Kuroda³, Takuma Sato³, Osamu Seguchi³, Masanobu Yanase³, and Norihide Fukushima³

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ²Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, and ³Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Objective: Tuberculosis is an important concern following organ transplantation. Unfortunately, several antituberculosis drugs interact with immunosuppressants. This report describes our experience with rifabutin (RBT) in the treatment of acute tuberculosis in a cardiac transplant recipient. Case: A 61-year-old cardiac transplant recipient developed tuberculosis meningitis during treatment of miliary tuberculosis. RBT was given for 27 days concomitantly with cyclosporine (CsA). CsA concentrations at 0 hour (C₀) decreased within 3 days of starting RBT. The serum concentration-curve from 0 to 12 hours (AUC_0–12h)/dose 7 days after starting RBT therapy decreased by 28%, compared to the values before RBT therapy. The apparent clearance at both 7 and 21 days after starting RBT therapy was 1.4 times higher than before RBT therapy. Conclusion: RBT has fewer drug-drug interactions than rifampin and should be preferentially used for the treatment of tuberculosis in transplant patients treated with CsA. Close monitoring of CsA blood concentration during RBT therapy minimized the risk of under- or over-immunosuppression in a cardiac transplant patient. Correspondence to:
Kyoichi Wada, PhD
Department of Pharmacy
National Cerebral and Cardiovascular Center
5-7-1,  Fujishirodai, Suita, 565-8565, Japan 
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 56 – No. 6/2018 (270-276)

Effect of fluconazole on the pharmacokinetics of everolimus and tacrolimus in a heart transplant recipient: Case report

Kazuki Nakagita¹#², Kyoichi Wada¹#², Yuka Terada¹, Sachi Matsuda¹, Nobue Terakawa¹, Akira Oita¹, and Mitsutaka Takada²

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, and ²Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, Osaka, Japan
Objective: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been used in combination with calcineurin inhibitors (tacrolimus and cyclosporine) to prevent allograft rejection following organ transplantation. In heart transplant recipients, everolimus should be maintained at a target blood concentration of 3 – 8 ng/mL, in combination with reduced-dose calcineurin inhibitors and therefore, requires strict monitoring. Fluconazole, an azole antifungal agent, affects blood concentration of tacrolimus by inhibiting the cytochromes P450 (CYP) 3A4 and 3A5. Therefore, to avoid overexposure during everolimus-azole cotreatment, the dose of everolimus should be reduced. However, the mechanism of interaction between everolimus and fluconazole remains unclear. Case report: We report the case of a heart transplant recipient who experienced a 2.8-fold increase in everolimus clearance and a 3.5-fold increase in everolimus dosage, following withdrawal of fluconazole therapy. The clearance and dosage of tacrolimus increased 4.7- and 3.0-fold, respectively. Conclusion: The concentrations of everolimus and tacrolimus should be carefully monitored when administered concomitantly with fluconazole to heart transplant recipients. The patient in this case had a CYP3A5*1/*3 genotype, and CYP3A5 constituted the metabolic pathway. Therefore, concomitant use of fluconazole might have a relatively small impact on everolimus and tacrolimus pharmacokinetics in this case. Correspondence to:
Kyoichi Wada, PhD 
Department of  Pharmacy
National Cerebral and Cardiovascular Center
5-7-1 Fujishirodai,  Suita 565-8565, Japan 
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 1/2019 (32-36)

Changes in blood concentration of mycophenolic acid and FK506 in a heart-transplant patient treated with plasmapheresis 

Shoji Kawauchi¹#², Kyoichi Wada²#³, and Akira Oita²

¹Educational Center for Clinical Pharmacy, Kobe Pharmaceutical University, Higashinada-ku, Kobe, ²Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, and ³Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, Osaka, Japan
Objective: Prior to heart transplant, sensitization to human leukocyte antigen can occur after blood transfusions used during implantation of ventricular assist devices. The result is an increased risk of antibody-mediated rejection (AMR) after heart transplant. While plasmapheresis (PPH) treats serious AMR cases, what subsequent changes occur in the blood concentrations of immunosuppressive agents is still unknown. We investigated pre- and post-PPH changes in blood concentrations of tacrolimus (FK506) and mycophenolic acid (MPA) in a heart-transplant patient experiencing AMR. Case: A 40-year-old woman with a history of dilated cardiomyopathy had heart transplantation for advanced heart failure. Since the patient was donor-specific antibody-positive and at risk for AMR, intravenous immunoglobulin therapy and PPH were performed just before transplantation. Triple combination immunosuppressive therapy was initiated, but 4 days after transplantation, panel-reactive antibody increased drastically, and AMR was diagnosed by biopsy. Multidisciplinary therapy, including PPH, was performed. Blood samples were collected to measure blood concentrations of FK506 and MPA before and after passage through the plasma separator. Results: The elimination efficiency of FK506 from PPH was –6.25 – 2.25%, while the elimination efficiency of MPA was much greater at 32.35 – 51.43%. Conclusion: These results show the necessity of carefully considering changes in blood concentrations that occur in immunosuppressive agents due to PPH, including the pharmacokinetics of the particular drug. However, proper timing of the PPH relative to drug administration can also minimize immunosuppressant loss. Correspondence to:
Kyoichi Wada, PhD
 Department of  Pharmacy
National Cerebral and  Cardiovascular Center
5-7-1 Fujishirodai,  Suita 565-8565, Japan
Email: kyowada@ gaps.oups.ac.jp

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 6/2019 (315-322)

Comparison of CYP3A5*3 genotyping assays for personalizing immunosuppressive therapy in heart transplant patients 

Takaya Uno¹#²#³, Kyoichi Wada¹#³, Sachi Matsuda¹, Yuka Terada¹#³, Akira Oita¹, Mitsutaka Takada²#³, Masanobu Yanase⁴, and Norihide Fukushima⁴

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, ²Division of Clinical Drug Informatics, Faculty of Pharmacy, ³Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, and ⁴Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Objective: This study aimed to compare a novel point-of-care assay that involves a flap endonuclease reaction performed using GTS-7000^® to a conventional assay that involves DNA sequencing performed using 3130xl Genetic Analyzers*. Materials and methods: This study enrolled 74 patients who underwent heart transplantation at the National Cerebral and Cardiovascular Center between May 2004 and October 2016. Each patient was genotyped as cytochrome P450 (CYP) 3A5*1/*1, CYP3A5*1/*3, or CYP3A5*3/*3. Quantitative and qualitative comparison between the two assays was carried out. Results: Four patients were genotyped as CYP3A5*1/*1, 25 as CYP3A5*1/*3, and 45 as CYP3A5*3/*3. Genotyping results of the point-of-care method were completely consistent with those of the conventional method. The total analysis time of the point-of-care method was shorter than that of the conventional method (~ 1.5 vs. 7.5 h). However, the cost of the point-of-care method was higher than that of the conventional method (~ 21 vs. 17 US$). Conclusion: Compared with a laboratory-based assay, the point-of-care assay that utilizes GTS-7000^® is accurate and rapid despite being slightly more expensive. Further trials using this assay are warranted.Correspondence to:
 Norihide Fukushima, PhD 
Department of Transplant Medicine
National Cerebral and Cardiovascular Center
5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 1/2021 (63-70)

Relationship between serum bepridil concentration and corrected QT interval 

Kazuki Matsui¹#²#³, Yutaro Mukai³, Kota Sakakura³, Kyoichi Wada⁴, Tsutomu Nakamura⁴, Atsufumi Kawabata², Nobue Terakawa³, Naoki Hayakawa³, Kengo Kusano⁵, Kouichi Hosomi⁶#⁷, Satoshi Yokoyama⁶#⁷, and Mitsutaka Takada¹#⁶#⁷

¹Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, ²Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, ³Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ⁴Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, ⁵Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, ⁶Division of Clinical Drug Informatics, Kindai University Graduate School of Pharmacy, and ⁷Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-Osaka, Japan
Objective: Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil.
Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. Patients with atrial fibrillation who were treated with bepridil from January 2014 to December 2015 were enrolled in the study. Serum bepridil concentrations and electrocardiogram data collected more than 21 days after the initiation of bepridil were used for analysis.
Results: A total of 60 patients were included in this study. There was a significant difference in mean QTc interval before and after initiation of bepridil (p < 0.0001). A significant relationship was observed between bepridil dose (p = 0.014) or serum bepridil concentration (p < 0.001) and QTc interval. Additionally, a significant relationship was observed between serum bepridil concentration and ΔQTc (p = 0.034). In the study, 4 patients developed QTc prolongation ≥ 500 ms after the initiation of bepridil. Serum bepridil concentration in this group was significantly higher compared with the group that did not display prolonged QTc (973 ± 651 vs. 526 ± 310 ng/mL, p = 0.01).
Conclusion: This study revealed that the QTc interval was significantly associated with serum bepridil concentration. Serum bepridil concentration beyond a therapeutic range may be a critical risk factor for developing QTc prolongation.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University Graduate School of Pharmacy
Higashi-Osaka, Osaka, 577-8502, Japan
Email:  takada@ phar.kindai.ac.jp

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 8/2021 (566-571)

Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients 

Megumi Ikura¹, Tsutomu Nakamura², Takaya Uno¹, Kazuki Nakagita¹, Hiromi Takenaka¹, Sachi Matsuda¹, Ryosuke Oda¹, Kyoichi Wada², Yuji Hattori¹, Osamu Seguchi³, Masanobu Yanase³, Naoki Hayakawa¹, and Norihide Fukushima³

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ²Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, and ³Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Objective: Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients.
Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis.
Results: A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment.
Conclusion: The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.Correspondence to:
Tsutomu Nakamura, PhD, Professor
Education and Research Center for Clinical Pharmacy
Faculty of Pharmacy, Osaka Medical and Pharmaceutical University
4-20-1 Nasahara, Takatsuki 569-1094, Japan
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 62 – No. 11/2024 (525-533)

Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy 

Megumi Ikura¹, Tsutomu Nakamura², Kyoichi Wada², Rikako Nagata¹, Tomoko Ueno¹, Kazuyoshi Kawabata¹, Fumiki Yoshihara³, Takuya Watanabe⁴, and Yasumasa Tsukamoto⁴

¹Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, ²Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, ³Department of Hypertension and Nephrology, and ⁴Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Objective: In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy.
Materials and methods: 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients. AKI was evaluated within 7 days of tacrolimus administration.
Results: The rate of increase in tacrolimus trough concentration to the target trough concentration of 10 µg/mL early after its administration was set to be similar in the basiliximab induction and non-induction group; 8 and 2 patients developed AKI in the induction and non-induction group, respectively. In the induction group, there was no significant difference in the timing of tacrolimus initiation and the time required to reach the target concentration between patients who developed and did not develop AKI. In contrast, the cumulative incidence of AKI was significantly different between patients with an estimated glomerular filtration rate below and those with an estimated glomerular filtration rate above 43 mL/min/1.73m² at the start of tacrolimus administration (37.5% and 11.4%, respectively; p = 0.045).
Conclusion: In patients receiving basiliximab induction therapy, the timing of tacrolimus initiation and the time to reach the target concentration are unlikely to be associated with early AKI after tacrolimus administration. However, the recovery of sufficient renal function after heart transplantation is important for determining the start time of tacrolimus.Correspondence to:
Tsutomu Nakamura, PhD, Professor
Education and Research Center for Clinical Pharmacy
Faculty of Pharmacy
Osaka Medical and Pharmaceutical University
4-20-1 Nasahara, Takatsuki 569-1094, Japan
Email: [email protected]

Abstract

Intern. Journal of Clinical Pharmacology and Therapeutics, Vol. 62 – No. 12/2024 – Corrigendum

Corrigendum for the article Int J Clin Pharmacol Ther 2024; 11: 525-533

Megumi Ikura, Tsutomu Nakamura, Kyoichi Wada, Rikako Nagata, Tomoko Ueno, Kazuyoshi Kawabata, Fumiki Yoshihara, Takuya Watanabe, and Yasumasa Tsukamoto

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