University of YamanashiYamanashi
University of YamanashiYamanashi
Tanaka T.,University of YamanashiYamanashi |
Okuyama-Dobashi K.,University of YamanashiYamanashi |
Murakami S.,Nagoya City University |
Chen W.,University of YamanashiYamanashi |
And 8 more authors.
Antiviral Research | Year: 2016
Current therapies for hepatitis B virus (HBV) cannot completely eliminate the HBV genome because of the stable population of covalently closed circular DNA (cccDNA) and so on. FIT-039, which is a cyclin-dependent kinase (CDK) 9 inhibitor, is known to suppress the replication of several DNA viruses including HSV, HPV and human adenovirus. In this study, we investigated the antiviral effect of FIT-039 on HBV infection. HepG2 cells expressing human sodium taurocholate cotransporting polypeptide (HepG2/NTCP cells) were infected with HBV in the presence of FIT-039. FIT-039 dose-dependently reduced intracellular viral RNA, nucleocapsid-associated viral DNA, and supernatant viral antigens without cytotoxicity in the infected cells (IC50 = 0.33 μM, CC50 > 50 μM). The antiviral activity of FIT-039 was prominent at an early phase of viral infection, although the compound did not inhibit preS1-binding to HepG2/NTCP cells. FIT-039 reduced cccDNA in HBV-replicating or HBV-infected cells. Furthermore, the antiviral activity of entecavir was significantly enhanced by the combination with FIT-039 in the chimeric mice having human hepatocytes infected with HBV. None of the mice had significant drug-related body weight or serum human-albumin concentration changes. These data suggest that CDK9 inhibitor FIT-039 is a promising antiviral candidate for HBV infection. © 2016 Elsevier B.V.
Gao S.,Shenyang University |
Gao S.,University of YamanashiYamanashi |
Zhang X.,University of YamanashiYamanashi |
Gao K.,University of YamanashiYamanashi |
And 5 more authors.
Cellular Signalling | Year: 2017
Gap junctions (GJs) play a major role in the control of cell structure, function, and metabolism. However, the molecular mechanisms involved are still poorly understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad range of cellular processes, we tested the possible involvement of TXNIP. Disruption of GJs with several chemical GJ inhibitors or connexin43 (Cx43) siRNA potently suppressed TXNIP, which was preceded by an activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK or its upstream kinase with chemical inhibitors prevented the reduction of TXNIP. On the contrary, activation of ERK with mitogens or phosphatase inhibitors reproduced the suppressive effects of GJs. Further analysis revealed that dysfunction of GJs promoted TXNIP phosphorylation, ubiquitination, and degradation, whereas inhibition of ERK exerted the opposite effects. Moreover, inhibition of GJs elevated Glut1 and enhanced cell resistance to ER stress in a similar way to TXNIP downregulation. Collectively, our study thus characterizes ERK-mediated suppression of TXNIP as a presently unreported mechanism by which GJs regulate cell behaviors. © 2017 Elsevier Inc.
Katayama-Hirayama K.,University of YamanashiYamanashi |
Suzuki A.,Engineering Group |
Mukaiyama S.,University of YamanashiYamanashi |
Kaneko H.,University of YamanashiYamanashi |
And 2 more authors.
Sustainable Environment Research | Year: 2010
Tetrabromobisphenol A (TBBPA) is one of the widely used flame retardants in industrial products such as plastic polymers and electronic circuits, and has the potential to enter the water environment after disposal of these products. We tried to remove TBBPA in water by slow sand filtration and UV irradiation. The removal efficiency of TBBPA in river water was relatively low at about 20% at an initial concentration of 100 μg L-1, and 2,6-dibromophenol was identified as a metabolite of TBBPA by slow sand filtetration. To eliminate TBBPA from water effectively, we employed a newly developed UV lamp system. The UV system has microwave-excited lamps. The output light is extremely stable with high luminescence intensity, and many advantages are brought about, such as low generation of heat and a long life compared with low-pressure mercury lamps in the conventional system. TBBPA degradation by UV irradiation was successfully performed in an aqueous solution of TBBPA. After 30 min irradiation, the initial concentration of TBBPA of 22 mg L-1 was decreased to 0, and a stoichiometric amount of bromide ion was released. A decrease in the concentration of dissolved organic carbon suggested mineralization of TBBPA. © 2010, Chinese Institute of Environmental Engineering. All rights reserved.
Iwashita Y.,Kumamoto University |
Iwashita Y.,Kumamoto Health Science University |
Kuwabara T.,Kumamoto University |
Hayata M.,Kumamoto University |
And 5 more authors.
American Journal of Physiology - Renal Physiology | Year: 2016
Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease. © 2016 the American Physiological Society.
Jin L.,University of YamanashiYamanashi |
Kobayashi D.,University of YamanashiYamanashi |
Kondoh E.,University of YamanashiYamanashi |
Kowa H.,Uniopt Co. |
Gelloz B.,Nagoya University
Optics Express | Year: 2016
In semiconductor and optics fields, some devices are constructed with layered systems including two or three individual layers. Measurement of polarization properties of the individual components of these layered systems is often desired. In this paper, we present methods allowing the simultaneous extraction of the polarization parameters of the individual components by analyzing spectroscopic Mueller matrices (measured at two wavelengths). We have studied both retarder-retarder and retarder-polarizer-retarder systems. The validities of the methods were successfully tested using both simulations and real polarization systems. ©2016 Optical Society of America.
Miyamoto T.,University of YamanashiYamanashi |
Honda R.,University of Tokyo
Life-Cycle of Structural Systems: Design, Assessment, Maintenance and Management - Proceedings of the 4th International Symposium on Life-Cycle Civil Engineering, IALCCE 2014 | Year: 2015
This paper introduces the concept of a "design set of input motions", a suite of various types of input motions which satisfy certain conditions for the seismic design. Diversity of input motions in the set is an index to evaluate the reliability of the design set. We construct a concrete scheme of setting design input motions based on the concept of design set. As the first stage, a set of design input motions which has appropriate degree of diversity is selected. For the practical purpose, however, we need to have some specific input motions to be utilized in the design. In the second stage, we present a method to synthesize an input motion which represents the design set. © 2015 Taylor & Francis Group, London.
Fukasawa M.,University of YamanashiYamanashi
Journal of Vascular Access | Year: 2015
Introduction: To promote the increase in patients undergoing peritoneal dialysis (PD) in Japan, the Japanese Society for Dialysis Access started offering workshops on peritoneal access (PA) preparation procedures for doctors with less experience. Since the transfer of technology used in surgical procedures is difficult in small communities such as individual hospitals, a specialist group such as a society should take the initiative and fulfill this responsibility. Methods: Here we used a hybrid simulator developed by Terumo Medical Pranex that uses the abdominal wall of an edible pig (a lump from the peritoneum to skin) and a mannequin. Since the structure of the porcine abdominal wall is similar to that of humans, the PA procedure can be simulated in this actual procedure. With three-dimensional reproduction of the Douglas pouch and other features of the pelvis using human computed tomography images, we created a system in which even drainage is possible if the catheter is well placed. Results: Using this simulator, students were able to experience the PA access preparation procedure 2-4 times and easily observed the catheter position after insertion by peeling the abdominal wall from the mannequin. Conclusions: In the future, by leveraging the advantages of the hybrid simulator, we aim to promote the training of medical staff interested in PD health care and increase the number of patients able to benefit from the many advantages of PD. © 2015 Wichtig Publishing.
Takai T.,Task Force for House Dust Mite Allergen Standardization |
Takai T.,Juntendo University |
Okamoto Y.,Task Force for House Dust Mite Allergen Standardization |
Okamoto Y.,Chiba UniversityChiba |
And 13 more authors.
Allergology International | Year: 2015
Abstract Background In the 1990s, the Japanese Society of Allergology (JSA) standardized Japanese cedar pollen allergen vaccines. In the present study, the task force for house dust mite (HDM) allergen standardization of the Committee for Allergens and Immunotherapy of JSA reports the standardization of HDM allergen vaccines in Japan. Methods In vivo allergenic potency was determined by intradermal testing of 51 Japanese adults with positive serum specific IgE to HDM allergens. In vitro total IgE binding potency was analyzed by competition ELISA using a pooled serum, with sera obtained from 10 allergic patients. The amounts of HDM group 1 (Der 1) and group 2 major allergens in eight HDM allergen extracts were measured by sandwich ELISAs. Correlation between the in vitro total IgE binding potency and major allergen levels was analyzed. Results We selected a JSA reference HDM extract and determined its in vivo allergenic potency. The in vitro total IgE binding potency significantly correlated with Der 1 content, group 2 allergen content, and their combined amount, indicating that measurement of major allergen contents can be used as a surrogate in vitro assay. Conclusions The task force determined the in vivo allergenic potency (100,000 JAU/ml) and Der 1 content (38.5 μg/ml) of the JSA reference HDM extract, selected the measurement of Der 1 content as the surrogate in vitro assay, and decided that manufacturers can label a HDM allergen extract as having a titer of 100,000 JAU/ml if it contains 22.2-66.7 μg/ml of Der 1. © 2015 Japanese Society of Allergology.
Osonoi T.,Naka Kinen ClinicIbaraki |
Saito M.,Naka Kinen ClinicIbaraki |
Hariya N.,University of YamanashiYamanashi |
Goto M.,Sanwa Kagaku Kenkyusho Co. |
Mochizuki K.,University of YamanashiYamanashi
Peptides | Year: 2016
Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin. Forty-two Japanese T2DM patients with inadequately controlled disease (HbA1c: 6.5%–8.0%) treated with metformin (n = 14), miglitol (n = 14) or a combination of the two drugs (n = 14) received additional treatment with anagliptin (100 mg, p.o., b.i.d.) for 52 weeks. We assessed glycemic control, postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of leptin in those patients. Add-on therapy with anagliptin for 52 weeks improved glycemic control and increased the area under the curve of biologically active GLP-1 concentration without altering obesity indicators. Total GIP concentration at 52 weeks was reduced by add-on therapy in groups treated with miglitol compared with those treated with metformin. Add-on therapy reduced leptin concentrations. Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration. © 2016 Elsevier Inc.
Motosugi U.,University of Wisconsin - Madison |
Motosugi U.,University of YamanashiYamanashi |
Bannas P.,University of Wisconsin - Madison |
Bannas P.,University of Hamburg |
And 4 more authors.
Magnetic Resonance in Medical Sciences | Year: 2016
Purpose: We performed a quantitative intraindividual comparison of the performance of 0.025- and 0.05-mmol/kg doses for gadoxetic acid-enhanced liver magnetic resonance (MR) imaging. Materials and Methods: Eleven healthy volunteers underwent liver MR imaging twice, once with a 0.025- and once with a 0.05-mmol/kg dose of gadoxetic acid. MR spectroscopy and 3-dimensional gradient-echo T1-weighted images (3D-GRE) were obtained before and 3, 10, and 20 min after injection of the contrast medium to measure T1 and T2 values and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) performance. During the dynamic phase, highly time-resolved 3D-GRE was used to estimate the relative CNR (CNRrel) of the hepatic artery and portal vein (PV) to the liver. We used paired t-tests to compare the results of different doses. Results: During the hepatobiliary phase, we observed shorter T1 values and higher SNRs of the liver (P < 0.001) and higher liver-to-PV and liver-to-muscle CNRs (P < 0.002) using 0.05 mmol/kg compared to 0.025 mmol/kg. Increasing the dose to 0.05 mmol/kg yielded a greater T1-shortening effect at 10 min delay even compared with 0.025 mmol/kg at 20 min (P < 0.001). During the dynamic phase, the peak CNRrel for the hepatic artery and portal vein were higher using 0.05 mmol/kg (P = 0.007 to 0.035). Conclusion: Use of gadoxetic acid at a dose of 0.05 mmol/kg leads to significantly higher SNR and CNR performance than with 0.025 mmol/kg. Quantitatively, a 10-min delay may be feasible for hepatobiliary-phase imaging when using 0.05 mmol/kg of gadoxetic acid. © 2015 Japanese Society for Magnetic Resonance in Medicine.