Kumamoto UniversityKumamoto

Kumamoto-shi, Japan

Kumamoto UniversityKumamoto

Kumamoto-shi, Japan
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Suzuki K.,St Vincents Center For Applied Medical Research | Hattori S.,Kumamoto UniversityKumamoto | Marks K.,St Vincents Center For Applied Medical Research | Ahlenstiel C.,University of New South Wales | And 10 more authors.
Molecular Therapy - Nucleic Acids | Year: 2013

Despite prolonged and intensive application, combined antiretroviral therapy cannot eradicate human immunodeficiency virus (HIV)-1 because it is harbored as a latent infection, surviving for long periods of time. Alternative approaches are required to overcome the limitations of current therapy. We have been developing a short interfering RNA (siRNA) gene silencing approach. Certain siRNAs targeting promoter regions of genes induce transcriptional gene silencing. We previously reported substantial transcriptional gene silencing of HIV-1 replication by an siRNA targeting the HIV-1 promoter in vitro. In this study, we show that this siRNA, expressed as a short hairpin RNA (shRNA) (shPromA-JRFL) delivered by lentiviral transduction of human peripheral blood mononuclear cells (PBMCs), which are then used to reconstitute NOJ mice, is able to inhibit HIV-1 replication in vivo, whereas a three-base mismatched variant (shPromA-M2) does not. In shPromA-JRFL–treated mice, HIV-1 RNA in serum is significantly reduced, and the ratio of CD4+/CD8+ T cells is significantly elevated. Expression levels of the antisense RNA strand inversely correlates with HIV-1 RNA in serum. The silenced HIV-1 can be reactivated by T-cell activation in ex vivo cultures. HIV-1 suppression is not due to offtarget effects of shPromA-JRFL. These data provide “proof-of principle” that an shRNA targeting the HIV-1 promoter is able to suppress HIV-1 replication in vivo. © 2013 American Society of Gene & Cell Therapy

Okada Y.,Kumamoto UniversityKumamoto | Aniya M.,Kumamoto UniversityKumamoto
Solid State Ionics | Year: 2015

Some solid electrolytes exhibit the non-Arrhenius type ionic conductivity whose origin is still not well understood. In the present study, a model for the non-Arrhenius ionic conductivity is proposed by exploiting the formulation of the bond strength-coordination number fluctuation (BSCNF) model developed originally to describe the transport properties of supercooled liquids. According to the present model, the origin of the non-Arrhenius ionic conductivity as described by the VFT equation traces back to the bonding energy fluctuations of the diffusing ions within the solid. The model suggests that good ionic conductors exhibit a non-Arrhenius behavior in the ionic conductivity. The present study reveals also that the degree of the non-Arrhenius behavior of different materials is separated roughly into two groups depending on the nature of the chemical bonds. One of these groups consists mainly of compounds such as Ag ion conductors, and the other group contains materials such as Li ion conductors. © 2015 Elsevier B.V.All rights reserved.

Pambudi N.A.,Semarang State UniversitySemarang | Torii S.,Kumamoto UniversityKumamoto | Saptoadi H.,Gadjah Mada UniversityYogyakarta | Sumbodo W.,Semarang State UniversitySemarang | And 2 more authors.
Sustainable Environment Research | Year: 2010

This paper described conversion of Jatropha curcas waste into solid fuel through densification. The J. curcas waste contains 61-67% cake seed per unit weight. The densification makes a cake seed easy to collect, ship, store and use. The cake seed is useful as a solid fuel. Initially, the waste was examined with proximate and heating value analyses which were used to identify moisture, volatile matter and ash contain. Next, the fixed bed reactor was adopted as the process of the combustion characteristic identification. The results showed that the increasing surface area per mass reduced the reaction time. Meanwhile, the increasing diameter of the cake seed pellet would result in decreasing combustion gas temperature. The diameter of the pellet did not influence CO emission significantly. The highest CO emission was found at the air flow veloocity of 0.1 m s−1 and temperature of 222 °C. © 2010, Chinese Institute of Environmental Engineering. All rights reserved.

Sakaguchi I.,Kumamoto UniversityKumamoto | Motohara T.,Kumamoto UniversityKumamoto | Saito F.,Kumamoto UniversityKumamoto | Takaishi K.,Kumamoto UniversityKumamoto | And 6 more authors.
Journal of Gynecologic Oncology | Year: 2015

Objective: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. Methods: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. Results: In the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). Conclusion: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease. © 2015. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Kurauchi Y.,Kumamoto UniversityKumamoto | Hisatsune A.,Kumamoto UniversityKumamoto | Seki T.,Kumamoto UniversityKumamoto | Katsuki H.,Kumamoto UniversityKumamoto
Brain Research | Year: 2016

Cerebrovascular endothelial cell dysfunction resulting in imbalance of cerebral blood flow contributes to the onset of psychiatric disorders such as depression, schizophrenia and bipolar disorder. Although decrease in Na+, K+-ATPase activity has been reported in the patients with schizophrenia and bipolar disorder, the contribution of Na+, K+-ATPase to endothelial cell dysfunction remains poorly understood. Here, by using rat neonatal prefrontal cortex slice cultures, we demonstrated that pharmacological inhibition of Na+, K+-ATPase by ouabain induced endothelial cell injury. Treatment with ouabain significantly decreased immunoreactive area of rat endothelial cell antigen-1 (RECA-1), a marker of endothelial cells, in a time-dependent manner. Ouabain also decreased Bcl-2/Bax ratio and phosphorylation level of glycogen synthase kinase 3β (GSK3β) (Ser9), which were prevented by lithium carbonate. On the other hand, ouabain-induced endothelial cell injury was exacerbated by concomitant treatment with LY294002, an inhibitor of phosphoinositide 3- (PI3-) kinase. We also found that xestospongin C, an inhibitor of inositol triphosphate (IP3) receptor, but not SEA0400, an inhibitor of Na+, Ca2+ exchanger (NCX), protected endothelial cells from cytotoxicity of ouabain. These results suggest that cerebrovascular endothelial cell degeneration induced by Na+, K+-ATPase inhibition resulting in Ca2+ release from endoplasmic reticulum (ER) and activation of GSK3β signaling underlies pathogenesis of these psychiatric disorders. © 2016 Elsevier B.V.

Kishimoto N.,Kumamoto UniversityKumamoto | Onitsuka-Kishimoto A.,Kumamoto UniversityKumamoto | Iga N.,Kumamoto UniversityKumamoto | Takamune N.,Kumamoto UniversityKumamoto | And 2 more authors.
Biochemistry and Biophysics Reports | Year: 2016

Human immunodeficiency virus type-1 (HIV-1) requires the packaging of human tRNALys3 as a primer for effective viral reverse transcription. Previously, we reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) suppresses the packaging efficiency of tRNALys3. Although the binding of GAPDH to Pr55gag is important for the suppression mechanism, it remains unclear which domain of GAPDH is responsible for the interaction with Pr55gag. In this study, we show that Asp256, Lys260, Lys263 and Glu267 of GAPDH are important for the suppression of tRNALys3 packaging. Yeast two-hybrid analysis demonstrated that the C-terminal domain of GAPDH (151–335) interacts with both the matrix region (MA; 1–132) and capsid N-terminal domain (CA-NTD; 133–282). The D256R, K263E or E267R mutation of GAPDH led to the loss of the ability to bind to wild-type (WT) MA, and the D256R/K260E double mutation of GAPDH resulted in the loss of detectable binding activity to WT CA-NTD. In contrast, R58E, Q59A or Q63A of MA, and E76R or R82E of CA-NTD abrogated the interaction with the C-terminal domain of GAPDH. Multiple-substituted GAPDH mutant (D256R/K260E/K263E/E267R) retained the oligomeric formation with WT GAPDH in HIV-1 producing cells, but the incorporation level of the hetero-oligomer was decreased in viral particles. Furthermore, the viruses produced from cells expressing the D256R/K260E/K263E/E267R mutant restored tRNALys3 packaging efficiency because the mutant exerted a dominant negative effect by preventing WT GAPDH from binding to MA and CA-NTD and improved the reverse transcription. These findings indicate that the amino acids Asp256, Lys260, Lys263 and Glu267 of GAPDH is essential for the mechanism of tRNALys3-packaging suppression and the D256R/K260E/K263E/E267R mutant of GAPDH acts in a dominant negative manner to suppress tRNALys3 packaging. © 2016 The Authors

Tokuda K.,Yamaguchi University | Kuramitsu Y.,Yamaguchi University | Byron B.,Yamaguchi University | Kitagawa T.,Yamaguchi University | And 6 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage. Immunohistological evaluations and immunoblotting confirmed the emergence of neuronal progenitor cells in the mature retina treated with glutamate. Proteomic analysis revealed the up-regulation of dihydropyrimidinase-related protein 3 (DRP-3), DRP-2 and stress-induced-phosphoprotein 1 (STIP1) during neural progenitor cell induction by glutamate. Moreover, mRNA expression of DRP-3, especially, its long isoform, robustly increased in the treated retina compared to that in the untreated retina. These results may indicate that glutamate induces neural progenitor cells in the mature rat retina by up-regulating the proteins which mediate cell mitosis and neurite growth. © 2015 Elsevier Inc.All rights reserved.

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