178 results on '"Kikuchi, Ryota"'
Search Results
152. Contribution of Organic Anion Transporter 3 (Slc22a8) to the Elimination of p-Aminohippuric Acid and Benzylpenicillin across the Blood-Brain Barrier
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Kikuchi, Ryota, primary, Kusuhara, Hiroyuki, additional, Sugiyama, Daisuke, additional, and Sugiyama, Yuichi, additional
- Published
- 2003
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153. In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia.
- Author
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Chiou, William J., de Morais, Sonia M., Kikuchi, Ryota, Voorman, Richard L., Li, Xiaofeng, and Bow, Daniel A. J.
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HYPERBILIRUBINEMIA ,BILIRUBIN ,GENOMES ,ATAZANAVIR ,CLINICAL trials - Abstract
1. Transient benign unconjugated hyperbilirubinemia has been observed clinically with several drugs including indinavir, cyclosporine, and rifamycin SV. Genome-wide association studies have shown significant association of OATP1B1 and UGT1A1 with elevations of unconjugated bilirubin, and OATP1B1 inhibition data correlated with clinical unconjugated hyperbilirubinemia for several compounds. 2. In this study, inhibition of OATP1B3 and UGT1A1, in addition to OATP1B1, was explored to determine whether one measure offers value over the other as a potential prospective tool to predict unconjugated hyperbilirubinemia. OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir. To investigate the intrinsic inhibition by the drugs, both in vivo Fi (fraction of intrinsic inhibition) and R-value (estimated maximum in vivo inhibition) for OATP1B1, OATP1B3 and UGT1A1 were calculated. 3. The results indicated that in vivo Fi values >0.2 or R-values >1.5 for OATP1B1 or OATP1B3, but not UGT1A1, are associated with previously reported clinical cases of drug-induced unconjugated hyperbilirubinemia. 4. In conclusion, inhibition of OATP1B1 and/or OATP1B3 along with predicted human pharmacokinetic data could be used pre-clinically to predict potential drug-induced benign unconjugated hyperbilirubinemia in the clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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154. Isotopic Diet Analysis of the Japanese Water Shrew Chimarrogale platycephala to Estimate Their Feeding Habits and the Usefulness of Body Hair Samples
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Shiozuka, Nao, Katano, Izumi, Kanzaki, Toko, Kikuchi, Ryota, Sato, Nozomu, Nakashita, Rumiko, Kudo, Seiya, Ikeda, Hiroshi, and Azuma, Nobuyuki
- Published
- 2023
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155. DNA Methylation and Histone Modification Profiles of Mouse Organic Anion Transporting Polypeptides
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Imai, Satoki, Kikuchi, Ryota, Kusuhara, Hiroyuki, and Sugiyama, Yuichi
- Abstract
Organic anion transporting polypeptides (rodents, Oatps; human, OATPs) are primarily involved in the transmembrane transportation of a wide range of endogenous and exogenous compounds. Multiple mouse Oatp1isoforms are closely located on chromosome 6, where each isoform shows distinct tissue distribution; Oatp1b2, Oatp1a6, and Oatp1c1 are expressed exclusively in the liver, kidney, and cerebrum, respectively; Oatp1a1 in the liver and kidney; and Oatp1a4 in the liver and cerebrum. We have identified tissue-dependent differentially methylated region (T-DMR) around the transcriptional start site (TSS) of Oatp1b2, which correlates with its liver-specific expression. Bisulfite sequencing also demonstrated the presence of T-DMRs around the TSS in other Oatp1genes: CpG dinucleotides at +149 relative to the TSS for Oatp1c1; −48, +101, and +356 for Oatp1a4; −572 and −550 for Oatp1a1; and −122 and +216 for Oatp1a6were differentially methylated among the liver, kidney, and cerebrum. These methylation profiles were largely consistent with the tissue distribution of Oatp1 mRNAs. Chromatin immunoprecipitation assay revealed that the mRNA expression of Oatp1genes was accompanied by acetylated histone H3. Human OATP1B1and OATP1B3are located on chromosome 12p12 in the OATP1cluster; both show predominant expression in the liver. These genes also contained T-DMRs that were hypomethylated in the liver, compared with kidney cortex: −511, −411, and +92 relative to the TSS for OATP1B1and −331, +70, and +73 for OATP1B3. These results suggest that the difference in epigenetic profiles comprising DNA methylation and histone acetylation determines the distinct tissue distribution of Oatp/OATP mRNAs.
- Published
- 2013
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156. Regulation of tissue-specific expression of renal organic anion transporters by hepatocyte nuclear factor 1 α/β and DNA methylation.
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Jin, Li, Kikuchi, Ryota, Saji, Takami, Kusuhara, Hiroyuki, and Sugiyama, Yuichi
- Abstract
We have reported previously that the kidney- and liver-specific expression of transporters in mice involves the coordinated regulation by hepatocyte nuclear factor 1 (HNF1) and DNA methylation. The present study was aimed at investigating the role of this cascade in the transcriptional regulation of renal organic anion transporters (OATs) yet to be characterized in human and mouse. Luciferase assays and electrophoretic mobility-shift assays demonstrated that HNF1α/β enhances the promoter activity of OAT4/SLC22A11 via binding to the HNF1 motif located near the transcriptional start site (TSS). DNA methylation profiles of human OAT1, OAT3, OAT4, and urate transporter 1 (URAT1) were determined in human liver and kidney cortex by bisulfite sequencing. Most of the CpG dinucleotides around the TSSs of OAT1 and OAT3 were highly methylated in the liver compared with kidney cortex, being consistent with their tissue specificity, whereas the difference in the DNA methylation status was less remarkable between the two tissues for OAT4 and URAT1. Mouse Oat1 gene also contained CpG dinucleotides hypomethylated in the kidney and hypermethylated in the liver downstream its TSS, whereas two of the seven CpG dinucleotides around the TSS of mouse Oat3 were significantly methylated in the liver compared with the kidney. Taken together, these findings underscored the central role of HNF1α/β in the transcriptional regulation of OATs and highlighted DNA methylation-dependent gene silencing as one of the mechanisms underlying the tissue-specific transactivation by this master regulator.
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- 2012
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157. Analysis of DNA Methylation and Histone Modification Profiles of Liver-Specific Transporters
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Imai, Satoki, Kikuchi, Ryota, Kusuhara, Hiroyuki, Yagi, Shintaro, Shiota, Kunio, and Sugiyama, Yuichi
- Abstract
Tissue-specific expression of transporters is tightly linked with their physiological functions through the regulation of the membrane transport of their substrates. We hypothesized that epigenetic regulation underlies the tissue-specific expression of mouse liver-specific transporters (Oatp1b2/Slco1b2, Ntcp/Slc10a1, Bsep/Abcb11, and Abcg5/g8). We examined their DNA methylation and histone modification profiles near the transcriptional start site (TSS) in the liver, kidney, and cerebrum. Genome-wide DNA methylation profiling with tissue-dependent differentially methylated region profiling with restriction tag-mediated amplification and subsequent bisulfite genomic sequencing demonstrated that the CpG dinucleotides around the TSS of Oatp1b2 (from -515 to +149 CpGs), Ntcp (from -481 to +495 CpGs), Bsep (from -339 to +282 CpGs), and Abcg5/g8 (from -161 to +5 CpGs for Abcg5, i.e., from -213 to -48 CpGs for Abcg8) were hypomethylated in the liver and hypermethylated in the kidney and cerebrum. The opposite pattern was observed for Pept2/Slc15a2 (from -638 to +4 CpGs), which was expressed in the kidney and cerebrum but not in the liver. These DNA methylation profiles are consistent with the tissue distribution of these transporters. A chromatin immunoprecipitation assay demonstrated that the histone H3 associated with Oatp1b2, Ntcp, Bsep, and Abcg5/g8 promoters was hyperacetylated in the liver but was acetylated very little in the kidney and cerebrum, whereas the upstream region of Pept2 was hyperacetylated only in the kidney and cerebrum. These results suggest the involvement of epigenetic systems in the tissue-specific expression of mouse transporters Oatp1b2, Ntcp, Bsep, Abcg5/g8, and Pept2.
- Published
- 2009
158. Transcriptional regulation of human and mouse organic anion transporter 1 by hepatocyte nuclear factor 1 alpha/beta.
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Saji, Takami, Kikuchi, Ryota, Kusuhara, Hiroyuki, Kim, Insook, Gonzalez, Frank J, and Sugiyama, Yuichi
- Abstract
Organic anion transporter 1 (OAT1/SLC22A6) is predominantly expressed in the proximal tubules of the kidney. Cumulative studies have shown its critical role in the tubular secretion of a variety of organic anions, including several clinically important drugs. In addition, OAT1 is also involved in the pharmacological effect of diuretics and the nephrotoxicity of antiviral drugs. In contrast to these functional characterizations, the regulatory mechanism of OAT1 expression is poorly understood. It was recently demonstrated that the expression of Oat1 was markedly reduced in the kidneys of hepatocyte nuclear factor 1alpha (Hnf1alpha)-null mice. However, in vitro evidence for the involvement of HNF1alpha and further analyses are required to illustrate the transcriptional regulation of OAT1 genes in more detail. Computational analysis of the potential transcription factor binding sites revealed that the HNF1-motif was conserved in the proximal-promoter region of human and mouse OAT1 genes. The mRNA expression of mouse organic anion transporter 1 was drastically reduced in Hnf1alpha-null mice compared with that in wild-type mice, which was consistent with a previous report (Maher et al., 2006). Forced expression of HNF1alpha alone or both HNF1alpha and HNF1beta enhanced the activity of human and mouse OAT1 promoters in the transactivation assays, whereas HNF1beta alone was not active. Mutations in the HNF1-motif significantly reduced this transactivation. Direct binding of HNF1alpha/HNF1alpha homodimer and HNF1alpha/HNF1beta heterodimer to the HNF1-motif found in the human OAT1 promoter was demonstrated by electrophoretic mobility shift assays. These results provide convincing evidence for the involvement of HNF1alpha/beta in the constitutive expression of human and mouse OAT1 in the kidney.
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- 2008
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159. Early intervention of plasma exchange combined with intensive immunosuppressive treatment for anti-MDA-5 antibody–positive rapidly progressive interstitial pneumonia: Two case reports.
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Ishiwari, Mayuko, Togashi, Yuki, Takoi, Hiroyuki, Kikuchi, Ryota, Kawagoe, Junichiro, Toriyama, Kazutoshi, Tanaka, Akane, Nagotomo, Yoko, Kinoshita, Hayato, Kono, Yuta, and Abe, Shinji
- Abstract
Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) has to be reported to often cause rapidly progressive interstitial lung disease (RP-ILD) especially in East Asian countries. Even with the recommended rapid administration of immunosuppressive agents with high-dose corticosteroids, intravenous pulse cyclophosphamide, and calcineurin inhibitors, the prognosis of anti-MDA5 Ab–related RP-ILD is poor. Plasma exchange (PE) has been reported to be effective for steroid-refractory RP-ILD with anti-MDA5 Ab. However, the timing, frequency, and interval of PE for the treatment of RP-ILD with anti-MDA5 Ab have not yet been established. We report two cases of RP-ILD with anti-MDA5 Ab treated by early intervention of PE combined with immunosuppressive treatment. Blood biomarkers including titers of anti-MDA5 Ab, serum KL-6 and ferritin were promptly decreased after each session of PE. Clinical symptoms, oxygenation and chest computed tomography abnormalities were completely improved after immunosuppressive treatment with PE. Early intervention of PE combined with immunosuppressive treatment may prevent the development to lethal severe respiratory failure in RP-ILD with anti-MDA5 Ab. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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160. Graph Classification of Molecules Using Force Field Atom and Bond Types.
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Jippo, Hideyuki, Matsuo, Tatsuru, Kikuchi, Ryota, Fukuda, Daisuke, Matsuura, Azuma, and Ohfuchi, Mari
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MOLECULAR graphs ,MOLECULAR force constants ,MOLECULAR dynamics ,SUPPORT vector machines ,STRUCTURE-activity relationships ,BIOLOGICAL classification ,CHEMICAL bonds - Abstract
Classification of the biological activities of chemical substances is important for developing new medicines efficiently. Various machine learning methods are often employed to screen large libraries of compounds and predict the activities of new substances by training the molecular structure‐activity relationships. One such method is graph classification, in which a molecular structure can be represented in terms of a labeled graph with nodes that correspond to atoms and edges that correspond to the bonds between these atoms. In a conventional graph definition, atomic symbols and bond orders are employed as node and edge labels, respectively. In this study, we developed new graph definitions using the assignment of atom and bond types in the force fields of molecular dynamics methods as node and edge labels, respectively. We found that these graph definitions improved the accuracies of activity classifications for chemical substances using graph kernels with support vector machines and deep neural networks. The higher accuracies obtained using our proposed definitions can enhance the development of the materials informatics using graph‐based machine learning methods. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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161. Sitagliptin-induced diffuse alveolar hemorrhage mimicking pulmonary edema.
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Kikuchi, Ryota, Nakamura, Hiroyuki, and Aoshiba, Kazutetsu
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SITAGLIPTIN , *HEMORRHAGE , *PULMONARY edema - Published
- 2018
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162. Real-Time Prediction of Wind Conditions and Atmospheric Turbulence for Safe and Efficient Aircraft Operation
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Kikuchi, Ryota and 大林茂
- Abstract
要約のみ, 課程
163. Reflectance comparison between Himawari-8 AHI and Terra MODIS over a forest of Shikoku region
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Goldberg, Mitchell, Chen, Jing M., Khanbilvardi, Reza, Adachi, Yusuke, Kikuchi, Ryota, Matsuoka, Masayuki, Ichii, Kazuhito, and Yoshioka, Hiroki
- Published
- 2018
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164. Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.
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Tsuji, Takao, Yamaguchi, Kazuhiro, Kikuchi, Ryota, Nakamura, Hiroyuki, Misaka, Ryoichi, Nagai, Atsushi, and Aoshiba, Kazutetsu
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OBSTRUCTIVE lung disease treatment , *METABOLIC disorders , *PULMONARY emphysema treatment , *PROSTAGLANDIN receptors , *ADIPOSE tissues , *COMORBIDITY , *HOMEOSTASIS - Abstract
Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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165. Coproporphyrin-I as a Selective OATP1B Biomarker Can Be Used to Delineate the Mechanisms of Complex Drug-Drug Interactions: Cedirogant Case Study.
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Kikuchi R, Qian Y, Badawi M, Savaryn JP, Gannu S, Eldred A, Hao S, Salem AH, Liu W, Klein CE, and Mohamed MF
- Abstract
Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus developed for the treatment of chronic plaque psoriasis. Cedirogant induces cytochrome P450 (CYP) 3A4 while inhibiting P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3 in vitro. Static drug-drug interactions (DDIs) predictions suggested possible clinical induction of CYP3A4, and inhibition of P-gp, BCRP, and OATP1B1, leading to challenges in interpreting DDI studies between cedirogant and substrates of CYP3A, P-gp, BCRP, and OATP1B1/3. Here the effects of cedirogant on the pharmacokinetics of two statin drugs were investigated in healthy participants. Coproporphyrin-I (CP-I), a selective endogenous OATP1B biomarker, was used to assess the impact of cedirogant on OATP1B. Cedirogant (375 mg once daily) increased rosuvastatin maximum plasma concentration (C
max ) and area under the plasma concentration curve (AUCtau ) by 141% and 55%, respectively when co-administered, whereas atorvastatin Cmax increased by 40% with no effect on its AUCtau compared with administration of rosuvastatin/atorvastatin alone. Cedirogant did not increase CP-I exposures, indicating no clinical OATP1B inhibition. The increased rosuvastatin exposure and minimal change in atorvastatin exposure with co-administration of cedirogant is attributed to BCRP inhibition and interplay between P-gp/BCRP inhibition and CYP3A induction, respectively. Correlation analysis with data from two investigational drugs (glecaprevir and flubentylosin) demonstrated that OATP1B1 R-value of > 1.5 and [Cmax,u ]/[OATP1B1 IC50 ] of > 0.1 are associated with > 1.25-fold increase in CP-I Cmax ratio. This demonstrates the utility of CP-I in disentangling mechanisms underlying a complex DDI involving multiple transporters and enzymes and proposes refined criteria for static OATP1B inhibition predictions., (© 2024 AbbVie Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2024
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166. Prognostic significance of antifibrotic agents in idiopathic pulmonary fibrosis after initiation of long-term oxygen therapy.
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Ishiwari M, Kono Y, Togashi Y, Kobayashi K, Kikuchi R, Kogami M, and Abe S
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Background and Aim: Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown., Methods: We retrospectively investigated favorable factors of survival in consecutive 55 IPF patients with chronic respiratory failure who were introduced LTOT., Results: The 6-, 12-, 18-, and 24-month survival rates in IPF patients after introduction of LTOT were 70.9%, 49.0%, 45.2%, and 32.3%, respectively. Univariate analysis demonstrated that low Glasgow Prognostic Score (GPS) (hazard ratio [HR] 0.482, p=0.043) and treatment with antifibrotic agents (HR 0.401, p=0.013) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 0.449, p=0.032). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0106)., Conclusion: In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.
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- 2024
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167. Impact of sarcopenia on chemotherapy-triggered exacerbation of interstitial lung disease in patients with non-small cell lung cancer.
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Kikuchi R, Takoi H, Ishiwari M, Toriyama K, Kono Y, Togashi Y, and Abe S
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- Humans, Prognosis, Retrospective Studies, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Diseases, Interstitial chemically induced, Lung Diseases, Interstitial complications, Lung Neoplasms complications, Lung Neoplasms drug therapy, Sarcopenia chemically induced
- Abstract
Background: While recent evidence has suggested that sarcopenia could predict chemotoxicity, its association with chemotherapy-triggered interstitial lung disease (ILD) exacerbations has yet to be investigated. Thus, the present study sought to determine whether sarcopenia could predict ILD exacerbations and overall survival (OS) in patients with ILD-complicated non-small cell lung cancer (NSCLC)., Methods: From January 2010 to July 2020, 74 patients with ILD-complicated NSCLC who received chemotherapy were retrospectively investigated. After categorizing patients according to the presence or absence of sarcopenia based on the psoas muscle index, ILD exacerbation rates and OS were evaluated., Results: Among the patients in the study, 39 were included in the sarcopenia group. Moreover, 17 (22.9%) patients developed ILD exacerbations, with the sarcopenia and nonsarcopenia groups having an exacerbation rate of 33.3% and 11.4%, respectively (p = 0.025). Multivariate analysis identified sarcopenia as an independent predictor of ILD exacerbations (p = 0.039). Furthermore, patients with sarcopenia demonstrated a significantly shorter median OS compared to those without the same (9.2 vs. 13.3 months; p = 0.029)., Conclusions: Sarcopenia predicted chemotherapy-triggered ILD exacerbation and OS in patients with ILD-complicated NSCLC, suggesting its utility in determining treatment approaches., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
- Published
- 2022
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168. Hypercapnia Accelerates Adipogenesis: A Novel Role of High CO 2 in Exacerbating Obesity.
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Kikuchi R, Tsuji T, Watanabe O, Yamaguchi K, Furukawa K, Nakamura H, and Aoshiba K
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- Adipocytes metabolism, Down-Regulation, Humans, Hypercapnia complications, Obesity complications, PPAR gamma metabolism, Adipocytes cytology, Adipogenesis physiology, Carbon Dioxide metabolism, Hypercapnia metabolism, Obesity metabolism
- Abstract
Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO
2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia. Adipogenesis was also induced under intermittent or sustained hypercapnia. Differentiated adipocytes were maintained to maturity under normocapnia or hypercapnia. Our main findings are as follows: (1) hypercapnia accelerated adipogenesis in visceral and subcutaneous preadipocytes, whereas hypocapnia inhibited adipogenesis; (2) hypercapnia did not affect adipocyte hypertrophy; (3) hypercapnia-accelerated adipogenesis was independent of extracellular acidosis, oxygen concentration, or either intermittent or sustained exposure to high CO2 ; and (4) the mechanisms underlying hypercapnia-accelerated adipogenesis involved increased production of cyclic adenosine monophosphate (cAMP) via soluble adenylyl cyclase, leading to the activation of protein kinase A and exchanger protein directly activated by cAMP, which, in turn, activated proadipogenic transcription factors, such as cAMP response element binding protein, CCAAT/enhancer binding protein β, and peroxisome proliferator-activated receptor γ. This study reveals a novel role of high CO2 in promoting adipogenesis, which provides mechanistic clues to a pathoetiological interaction between OSA/OHS and obesity. Our data suggest a vicious cycle of disease progression via the following mechanism: OSA/OHS → hypoventilation → hypercapnia → increased adipogenesis → increased fat mass → exacerbated OSA/OHS.- Published
- 2017
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169. Development of the Japanese version of the Pediatric Quality of Life Inventory ™ Transplant Module.
- Author
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Kikuchi R, Mizuta K, Urahashi T, Sanada Y, Yamada N, Onuma E, Ono M, Endo M, Sato I, and Kamibeppu K
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- Adolescent, Child, Child, Preschool, Female, Humans, Japan, Male, Reproducibility of Results, Surveys and Questionnaires, Liver Transplantation psychology, Parents psychology, Psychometrics methods, Quality of Life psychology
- Abstract
Background: Health-related quality of life (HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory
™ (PedsQL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity., Methods: Based on the PedsQL linguistic validation process, the Japanese version of the PedsQL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population., Results: Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3-7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed., Conclusions: Excellent feasibility, reliability, and validity of this Japanese self-report version of the PedsQL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the PedsQL Transplant Module is appropriate for use in clinical and research settings., (© 2016 Japan Pediatric Society.)- Published
- 2017
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170. Hypertrophic Osteoarthropathy Secondary to Lung Cancer: Beneficial Effect of Anti-vascular Endothelial Growth Factor Antibody.
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Kikuchi R, Itoh M, Tamamushi M, Nakamura H, and Aoshiba K
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- Adenocarcinoma of Lung, Angiogenesis Inhibitors administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cyclooxygenase 2 metabolism, Humans, Male, Middle Aged, Neoplasm Staging, Superior Vena Cava Syndrome diagnosis, Superior Vena Cava Syndrome etiology, Treatment Outcome, Vascular Endothelial Growth Factor A antagonists & inhibitors, Vascular Endothelial Growth Factor A metabolism, Adenocarcinoma complications, Adenocarcinoma metabolism, Adenocarcinoma pathology, Bevacizumab administration & dosage, Bone and Bones diagnostic imaging, Lung Neoplasms complications, Lung Neoplasms metabolism, Lung Neoplasms pathology, Osteoarthropathy, Secondary Hypertrophic diagnosis, Osteoarthropathy, Secondary Hypertrophic etiology, Radiography methods, Radionuclide Imaging methods, Radiotherapy, Intensity-Modulated methods
- Published
- 2017
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171. Salivary Gland Enlargement as an Unusual Imaging Manifestation of Granulomatosis With Polyangiitis Involving the Head and Neck Region.
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Kikuchi R, Aoshiba K, and Nakamura H
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- Aged, Granulomatosis with Polyangiitis complications, Humans, Male, Tomography, X-Ray Computed, Granulomatosis with Polyangiitis diagnostic imaging, Salivary Gland Diseases diagnostic imaging, Salivary Gland Diseases etiology
- Published
- 2016
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172. Health-related quality of life in parents of pediatric solid organ transplant recipients in Japan.
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Kikuchi R, Ono M, Kinugawa K, Endo M, Mizuta K, Urahashi T, Ihara Y, Yoshida S, Ito S, and Kamibeppu K
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- Adult, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Infant, Japan, Male, Middle Aged, Quality of Life, Regression Analysis, Retrospective Studies, Social Support, Surveys and Questionnaires, Time Factors, Transplant Recipients, Organ Transplantation psychology, Parents psychology
- Abstract
Few studies have examined HRQOL in pediatric Tx recipients' parents. This study investigated HRQOL in these parents and relationships between HRQOL and perceived burden of nurturing, family functioning, and social support. Self-report anonymous questionnaires and a survey of medical records were completed between September and December 2013. The SF-36v2, which evaluates physical, psychological, and social health, was used to measure HRQOL. While values for physical and psychological health were higher than standard values (Cohen's d = 0.34 and 0.17, respectively), social health scores were lower (d = 0.21). "Parental consultation unrelated to donation" (standardized partial regression coefficient: β = -0.52) was associated with physical health. "Family functioning" and "Commuting time between home and primary follow-up hospital" (β = 0.57 and -0.31) were related to psychological health. "Total score for perceived burden of nurturing" (β = -0.31) was related to social health. Regarding parental HRQOL, while physical and psychological health was favorable, social health was impaired. In clinical practice, interventions targeting parents' physical conditions and facilitation of community and family understanding and support to share recipients' nurturing are important in improving parental HRQOL., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
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173. Repeated exposure to 5-bromo-2'-deoxyuridine causes decreased proliferation and low-grade inflammation in the lungs of mice.
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Tsuji T, Itoh M, Kikuchi R, Uruma T, Watanabe H, Yamaguchi K, Nakamura H, and Aoshiba K
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- Animals, Bromodeoxyuridine administration & dosage, Fluorescent Antibody Technique, Lung drug effects, Lung pathology, Macrophages drug effects, Male, Mice, Mice, Inbred C57BL, Pneumonia pathology, Pulmonary Alveoli drug effects, Respiratory Mucosa drug effects, Respiratory Mucosa pathology, T-Lymphocytes drug effects, Bromodeoxyuridine adverse effects, Cell Proliferation drug effects, Pneumonia chemically induced
- Abstract
Incorporation of 5-bromo-2'-deoxyuridine (BrdU) into proliferating cells has been used to label dividing cells in many tissues. Although BrdU has been shown to be genotoxic, teratogenic and mutagenic, such adverse effects have largely been ignored by researchers. We determined whether long-term BrdU exposure causes any histopathological changes in the lungs of mice. Eight-week-old male C57/BL6J mice were administered BrdU by intraperitoneal injection on 3 consecutive days of each week for 14 weeks. While no obvious structural changes such as tissue damage, fibrosis, emphysema, airway remodeling, vascular thickening or tumorigenesis were noted, a moderate degree of macrophage infiltration was observed in the airways and lung parenchyma in the lungs of the mice exposed repeatedly to BrdU (BrdU-exposed mice). The proliferative activities of the airway and alveolar epithelial and mesenchymal cells were reduced in the BrdU-exposed mice, although the numbers of these cells in the lungs were maintained. Double immunofluorescence study of the lungs of the BrdU-exposed mice showed overexpression of IL-6 in the airway epithelial and alveolar wall cells, some of which were also double-positive for BrdU. These results indicate that long-term exposure to BrdU inhibits cell proliferation and induces low-grade inflammation in the lungs of mice. Our findings underscore the need for caution in the interpretation of studies that involve long-term exposure to BrdU., (Copyright © 2015 Elsevier GmbH. All rights reserved.)
- Published
- 2015
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174. Parents' quality of life and family functioning in pediatric organ transplantation.
- Author
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Kikuchi R and Kamibeppu K
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Male, Organ Transplantation statistics & numerical data, Pediatrics, Tissue and Organ Procurement methods, Young Adult, Family Relations psychology, Organ Transplantation psychology, Parent-Child Relations, Parents psychology, Quality of Life
- Abstract
Solid organ transplantation is an important treatment option for pediatric patients in end-stage organ failure. The impact of pediatric organ transplantation on parents' quality of life and family functioning has been found to be substantial, but findings on this topic have not previously been consolidated. Thirty-one studies were selected for analysis after a database search on this topic. We present future research questions and suggestions to improve clinical practice based on the integration of this knowledge., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
175. Prediction of clinical drug-drug interactions of veliparib (ABT-888) with human renal transporters (OAT1, OAT3, OCT2, MATE1, and MATE2K).
- Author
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Kikuchi R, Lao Y, Bow DA, Chiou WJ, Andracki ME, Carr RA, Voorman RL, and De Morais SM
- Subjects
- Animals, Benzimidazoles blood, Cell Line, Humans, Mice, Mice, Knockout, Models, Biological, Organic Anion Transporters, Sodium-Independent antagonists & inhibitors, Organic Cation Transport Proteins antagonists & inhibitors, Organic Cation Transport Proteins genetics, Benzimidazoles metabolism, Benzimidazoles pharmacokinetics, Kidney metabolism, Organic Anion Transporters, Sodium-Independent metabolism, Organic Cation Transport Proteins metabolism
- Abstract
Veliparib (ABT-888) is largely eliminated as parent drug in human urine (70% of the dose). Renal unbound clearance exceeds glomerular filtration rate, suggesting the involvement of transporter-mediated active secretion. Clinically relevant pharmacokinetic interactions in the kidney have been associated with OAT1, OAT3, OCT2, MATE1, and MATE2K. In the present study, interactions of veliparib with these transporters were investigated. Veliparib inhibited OAT1, OAT3, OCT2, MATE1, and MATE2K with IC50 values of 1371, 505, 3913, 69.9, and 69.5 μM, respectively. The clinical unbound maximum plasma concentration of veliparib after single oral dose of 50 mg (0.45 μM) is manyfold lower than IC50 values for OAT1, OAT3, OCT2, MATE1, or MATE2K. These results indicate a low potential for drug-drug interaction (DDI) with OAT1/3, OCT2, or MATE1/2K. Additional studies demonstrated that veliparib is a substrate of OCT2. In Oct1/Oct2 double-knockout mice, the plasma exposure of veliparib was increased by 1.5-fold, and the renal clearance was decreased by 1.8-fold as compared with wild-type mice, demonstrating that organic cation transporters contribute to the renal elimination in vivo. In summary, the in vitro transporter data for veliparib predicts minimal potential for an OAT1/3-, OCT2-, and MATE1/2K-mediated DDI given the clinical exposure after single oral dose of 50 mg., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2013
- Full Text
- View/download PDF
176. Epigenetic regulation of organic anion transporting polypeptide 1B3 in cancer cell lines.
- Author
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Imai S, Kikuchi R, Tsuruya Y, Naoi S, Nishida S, Kusuhara H, and Sugiyama Y
- Subjects
- Cell Line, Cell Line, Tumor, DNA Methylation, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Epigenesis, Genetic, Humans, Neoplasms metabolism, Organic Anion Transporters, Sodium-Independent metabolism, RNA Interference, RNA, Messenger genetics, Solute Carrier Organic Anion Transporter Family Member 1B3, Gene Expression Regulation, Neoplastic, Neoplasms genetics, Organic Anion Transporters, Sodium-Independent genetics
- Abstract
Purpose: The expression of a multispecific organic anion transporter, OATP1B3/SLCO1B3, is associated with clinical prognosis and survival of cancer cells. The aims of present study were to investigate the involvement of epigenetic regulation in mRNA expression of a cancer-type variant of OATP1B3 (Ct-OATP1B3) in cancer cell lines., Methods: The membrane localization and transport functions of Ct-OATP1B3 were investigated in HEK293 cells transiently expressing Ct-OATP1B3. DNA methylation profiles around the transcriptional start site of Ct-OATP1B3 in cancer cell lines were determined. The effects of a DNA methyltransferase inhibitor and siRNA knockdown of methyl-DNA binding proteins (MBDs) on the expression of Ct-OATP1B3 mRNA were investigated., Results: 5'-RACE identified the TSS of Ct-OATP1B3 in PK-8 cells. Ct-OATP1B3 was localized on the plasma membrane, and showed the transport activities of E217βG, fluvastatin, rifampicin, and Gd-EOB-DTPA. The CpG dinucleotides were hypomethylated in Ct-OATP1B3-positive cell lines (DLD-1, TFK-1, PK-8, and PK-45P) but were hypermethylated in Ct-OATP1B3-negative cell lines (HepG2 and Caco-2). Treatment with a DNA methyltransferase inhibitor and siRNA knockdown of MBD2 significantly increased the expression of Ct-OATP1B3 mRNA in HepG2 and Caco-2., Conclusions: Ct-OATP1B3 is capable of transporting its substrates into cancer cells. Its mRNA expression is regulated by DNA methylation-dependent gene silencing involving MBD2.
- Published
- 2013
- Full Text
- View/download PDF
177. DNA methylation profiles of organic anion transporting polypeptide 1B3 in cancer cell lines.
- Author
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Ichihara S, Kikuchi R, Kusuhara H, Imai S, Maeda K, and Sugiyama Y
- Subjects
- Cell Line, Tumor, CpG Islands, Deoxycytidine pharmacology, Humans, RNA, Messenger genetics, Solute Carrier Organic Anion Transporter Family Member 1B3, Transcription Factors genetics, Transcriptional Activation, DNA Methylation, Gene Expression Regulation, Neoplastic, Neoplasms genetics, Organic Anion Transporters, Sodium-Independent genetics
- Abstract
Purpose: Multispecific organic anion transporter, OATP1B3/SLCO1B3, is expressed in several cancer cell lines as well as tumor tissues, and its expression sensitizes the cells to some anti-cancer agents. The present study was aimed to characterize the DNA methylation profiles around the transcriptional start site (TSS) of OATP1B3 and correlate them with the mRNA expression in cancer and immortalized cell lines., Methods: The mRNA expression and DNA methylation profiles of OATP1B3 were determined by RT-PCR and bisulfite sequencing, respectively., Results: The expression of OATP1B3 mRNA was detected in DLD-1, TFK-1, PK-8, and PK-45P cells, but below the limit of detection in HepG2, Caco-2, and HEK293 cells. Bisulfite sequencing demonstrated that CpG dinucleotides around the TSS are differentially methylated among cell lines and partly associated with the mRNA expression profile of OATP1B3. Furthermore, treatment with 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferase, significantly increased the mRNA expression of OATP1B3 in HepG2 and Caco-2 cells by 18- and 14-fold, respectively, but not in DLD-1 and TFK-1 cells., Conclusion: DNA methylation-dependent gene silencing is at least partly involved in the regulation of OATP1B3 expression in cancer/immortalized cell lines.
- Published
- 2010
- Full Text
- View/download PDF
178. Regulation of tissue-specific expression of the human and mouse urate transporter 1 gene by hepatocyte nuclear factor 1 alpha/beta and DNA methylation.
- Author
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Kikuchi R, Kusuhara H, Hattori N, Kim I, Shiota K, Gonzalez FJ, and Sugiyama Y
- Subjects
- Animals, Base Sequence, Cell Line, Female, Gene Expression Regulation physiology, Hepatocyte Nuclear Factor 1-alpha biosynthesis, Hepatocyte Nuclear Factor 1-alpha genetics, Hepatocyte Nuclear Factor 1-beta biosynthesis, Hepatocyte Nuclear Factor 1-beta genetics, Humans, Male, Mice, Mice, Knockout, Molecular Sequence Data, Organic Anion Transporters genetics, Organic Cation Transport Proteins genetics, Tissue Distribution genetics, Transcriptional Activation genetics, DNA Methylation, Hepatocyte Nuclear Factor 1-alpha physiology, Hepatocyte Nuclear Factor 1-beta physiology, Organic Anion Transporters biosynthesis, Organic Cation Transport Proteins biosynthesis
- Abstract
Expression of Urate transporter 1 (URAT1/SLC22A12) is restricted to the proximal tubules in the kidney, where it is responsible for the tubular reabsorption of urate. To elucidate the mechanism underlying its tissue-specific expression, the transcriptional regulation of the hURAT1 and mUrat1 genes was investigated. Hepatocyte nuclear factor 1 alpha (HNF1alpha) and HNF1beta positively regulate minimal promoter activity of the URAT1 gene as shown by reporter gene assays. Electrophoretic mobility shift assays revealed binding of HNF1alpha and/or HNF1beta to the HNF1 motif in the hURAT1 promoter. Furthermore, the mRNA expression of Urat1 is reduced in the kidneys of Hnf1alpha-null mice compared with wild-type mice, confirming the indispensable role of HNF1alpha in the constitutive expression of URAT1 genes. It was also shown that the proximal promoter region of mUrat1 was hypermethylated in the liver and kidney medulla, whereas this region was relatively hypomethylated in the kidney cortex. These methylation profiles are in a good agreement with the proximal tubule-restricted expression of mUrat1 in the kidney cortex. Taken together, these results strongly suggest that tissue-specific expression of the URAT1 genes is coordinately regulated by the transcriptional activation by HNF1alpha/HNF1beta heterodimer and repression by DNA methylation.
- Published
- 2007
- Full Text
- View/download PDF
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