Yokohama-shi, Japan
Yokohama-shi, Japan

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Khalaj M.,U.S. National Institutes of Health | Abbasi A.,U.S. National Institutes of Health | Akiyama K.,Okayama University | Kikuchi S.,Yokohama University | And 8 more authors.
Journal of Biological Chemistry | Year: 2014

Background: Rev7 encodes a subunit of Pol for translesion DNA synthesis (TLS). Results: We found a Rev7 mutation in mice that causes developmental defects and increases susceptibility for genotoxicity. Conclusion: Rev7 is essential for mouse development through its function in cell proliferation. Significance: These findings demonstrate a unique function of Pol in development that is absent in other TLS polymerases. Repro22 is a mutant mouse produced via N-ethyl-N-nitrosourea- induced mutagenesis that shows sterility with germ cell depletion caused by defective proliferation of primordial germ cells, decreased body weight, and partial lethality during embryonic development. Using a positional cloning strategy, we identified a missense mutation in Rev7/Mad2l2 (Rev7C70R) and confirmed that the mutation is the cause of the defects in repro22 mice through transgenic rescue with normal Rev7. Rev7/Mad2l2 encodes a subunit of DNA polymerase (Pol), 1 of 10 translesion DNA synthesis polymerases known in mammals. The mutant REV7 did not interact with REV3, the catalytic subunit of Pol. Rev7C70R/C70R cells showed decreased proliferation, increased apoptosis, and arrest in S phase with extensive γH2AX foci in nuclei that indicated accumulation of DNA damage after treatment with the genotoxic agent mitomycin C. The Rev7C70R mutation does not affect the mitotic spindle assembly checkpoint. These results demonstrated that Rev7 is essential in resolving the replication stalls caused by DNA damage during S phase. We concluded that Rev7 is required for primordial germ cell proliferation and embryonic viability and development through the translesion DNA synthesis activity of Pol preserving DNA integrity during cell proliferation, which is required in highly proliferating embryonic cells.© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.


Iwai T.,Kanagawa University | Matsui Y.,Kagawa University | Omura S.,Yokohama University | Tohnai I.,Kanagawa University
Journal of Craniofacial Surgery | Year: 2012

Because navigational guidance can localize the operative site 3-dimensionally during maxillofacial surgery and provide precision, reliability, and safety for surgeons, we report Le Fort I osteotomy under navigational guidance for posterior repositioning of the maxilla. Copyright © 2012 Mutaz B. Habal, MD.


Shevtsova V.,MRC | Mialdun A.,MRC | Kawamura H.,Tokyo University of Science | Ueno I.,Tokyo University of Science | And 2 more authors.
Fluid Dynamics and Materials Processing | Year: 2011

The experimental results from nine benchmark test cases conducted by five different groups are presented. The goal of this study is to build an experimental database for validation of numerical models in liquid bridge geometry. The need arises as comparison of numerical results with a single experiment can lead to a large discrepancy due to specific experimental conditions. Perfectly conducting rigid walls and, especially, idealized boundary conditions at the free surface employed in numerical studies are not always realized in experiments. The experimental benchmark has emphasized strong sensitivity of the threshold of instability to the liquid bridge shape. A clear distinction should be made between results belonging to the different disturbance patterns, i.e. different wave numbers. The results of benchmark contributors are in a satisfactory agreement when they are associated with the stability branch with an identical wave number. In this case the discrepancy of the results for determination of the critical parameters is about ±15%-18% and they can be used for the validation of numerical models. © 2011 Tech Science Press.


Nam J.L.,University of Leeds | Ramiro S.,University of Amsterdam | Ramiro S.,Hospital Garcia Of Orta | Gaujoux-Viala C.,University of Nimes | And 11 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) Task Force treatment recommendations. Methods Medline, Embase and Cochrane databases were searched for articles published between January 2009 and February 2013 on infliximab, etanercept, adalimumab, certolizumab-pegol, golimumab, anakinra, abatacept, rituximab, tocilizumab and biosimilar DMARDs (bsDMARDs) in phase 3 development. Abstracts from 2011 to 2012 American College of Rheumatology (ACR) and 2011-2013 EULAR conferences were obtained. Results Fifty-one full papers, and 57 abstracts were identified. The randomised controlled trials (RCT) confirmed the efficacy of bDMARD+conventional synthetic DMARDs (csDMARDs) versus csDMARDs alone (level 1B evidence). There was some additional evidence for the use of bDMARD monotherapy, however bDMARD and MTX combination therapy for all bDMARD classes was more efficacious (1B). Clinical and radiographic responses were high with treat-to-target strategies. Earlier improvement in signs and symptoms were seen with more intensive initial treatment strategies, but outcomes were similar upon addition of bDMARDs in patients with insufficient response to MTX. In general, radiographic progression was lower with bDMARD use, mainly due to initial treatment effects. Although patients may achieve bDMARD- and drug-free remission, maintenance of clinical responses was higher with bDMARD continuation (1B), but bDMARD dose reduction could be applied (1B). There was still no RCT data for bDMARD switching. Conclusions The systematic literature review confirms efficacy of biological DMARDs in RA. It addresses different treatment strategies with the potential for reduction in therapy, particularly with early disease control, and highlights emerging therapies.


Saitoh Y.,Yokohama University | Hikake T.,International University of Japan | Hayashi S.,Yokohama University | Iguchi T.,Graduate University for Advanced Studies | And 3 more authors.
Cell and Tissue Research | Year: 2010

Estradiol (E2) stimulates not only secretion of prolactin (PRL) and proliferation of PRL-producing cells (PRL cells) in the anterior pituitary, but also the expression of growth factors. In insulin-like growth factor-I (IGF-I) knockout (KO) mice, the number of PRL cells is decreased and administration of IGF-I does not increase either the number of PRL cells or plasma PRL levels, indicating that IGF-I plays a pivotal role in PRL cells. The effect of E2 on PRL cells in KO mice was investigated by immunohisto-chemistry and real-time RT-PCR. The number of PRL cells in KO mice was significantly lower than in the wild-type (WT) control mice. E2 increased the PRL mRNA in WT and KO mice; however, an increase of PRL mRNA in KO was less than that in WT. In addition, no vasoactive intestinal peptide (VIP)-immunoreactive cells were found in KO mice, therefore IGF-I is essential for VIP expression. To investigate the roles of IGF-I on PRL cells in the postnatal development, double-immunostaining with PRL and BrdU was performed in WT and KO mice from days 5-20. The percentages of PRL cells and BrdU-labeled cells in the anterior pituitary of KO mice were lower than in WT mice. Thus, IGF-I may be responsible for proliferation and differentiation of PRL cells in this postnatal period. Differentiation and the proliferation of PRL cells are controlled by IGF-I during the postnatal development, and IGF may be a mediator of E2 action through VIP induction in PRL cells of adults. © Springer-Verlag 2010.


Hasegawa S.,Kanagawa Cancer Center | Hasegawa S.,Yokohama University | Yoshikawa T.,Kanagawa Cancer Center | Yoshikawa T.,Yokohama University | And 18 more authors.
Annals of Surgical Oncology | Year: 2013

Objective. The purpose of this study was to clarify the priority of nodal dissection in Siewert types II and III adenocarcinoma of the esophagogastric junction (AEG). Methods. The priority of nodal dissection was evaluated based on the therapeutic value index calculated by multiplying of the frequency of metastasis to each station and the 5-year survival rate of patients with metastasis to that station. Results. A total of 176 patients (95 type II and 81 type III) were examined. Among the lymph nodes that had a metastatic incidence exceeding 10 %, the stations showing the first to fourth highest index were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the node at the root of the left gastric artery (No. 7) in the total cohort, as well as in each type. The next station was the lower thoracic paraesophageal lymph node (No. 110), followed by the nodes along the proximal splenic artery (No. 11p) in type II, whereas it was the nodes along the proximal splenic artery (No. 11p) followed by the para-aortic nodes (No. 16a2), the nodes at the celiac artery (No. 9), and the nodes around the splenic hilum (No. 10) in type III. Conclusions. These results suggest that the highest priority nodal stations to be dissected were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the nodes at the root of the left gastric artery (No. 7), regardless of the Siewert subtype, but the subsequent priority was different depending on the subtype. © Society of Surgical Oncology 2013.


Omnus D.J.,Hannover Medical School | Omnus D.J.,University of Stockholm | Mehrtens S.,Hannover Medical School | Ritter B.,Hannover Medical School | And 5 more authors.
Journal of Molecular Biology | Year: 2011

Heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP) 1 was implicated in cap-independent translation by binding to the internal ribosome entry site in the 5′ untranslated region (UTR) of NF-κB-repressing factor (NRF). Two different NRF mRNAs have been identified so far, both sharing the common 5′ internal ribosome entry site but having different length of 3′ UTRs. Here, we used a series of DNA and RNA luciferase reporter constructs comprising 5′, 3′ or both NRF UTRs to study the effect of JKTBP1 on translation of NRF mRNA variants. The results indicate that JKTBP1 regulates the level of NRF protein expression by binding to both NRF 5′ and 3′ UTRs. Using successive deletion and point mutations as well as RNA binding studies, we define two distinct JKTBP1 binding elements in NRF 5′ and 3′ UTRs. Furthermore, JKTBP1 requires two distinct RNA binding domains to interact with NRF UTRs and a short C-terminal region for its effect on NRF expression. Together, our study shows that JKTBP1 contributes to NRF protein expression via two disparate mechanisms: mRNA stabilization and cap-independent translation. By binding to 5′ UTR, JKTBP1 increases the internal translation initiation in both NRF mRNA variants, whereas its binding to 3′ UTR elevated primarily the stability of the major NRF mRNA. Thus, JKTBP1 is a key regulatory factor linking two pivotal control mechanisms of NRF gene expression: the cap-independent translation initiation and mRNA stabilization. © 2011 Elsevier Ltd.


Okuno Y.,Yokohama University | Isomura S.,Yokohama University | Sugamata A.,Yokohama University | Tamahori K.,Yokohama University | And 5 more authors.
ChemSusChem | Year: 2015

The utility and applicability of polyethylene-g-polyacrylic acid-immobilized dimethylaminopyridine (g-DMAP) as a catalyst in a continuous-flow system were investigated for decarboxylative esterification. High catalytic activity toward acylation was provided by g-DMAP containing a flexible grafted-polymer structure. During decarboxylation, carboxylic acids and alcohols were converted cleanly using di-tert-butyl dicarbonate (Boc2O) as a coupling reagent, which reduced by-products. In addition, the use of Boc2O resulted in the formation of tert-butyl esters. These esterifications dramatically reduced the reaction time under continuous-flow conditions, with a residence time of approximately 2 min. This highly efficient esterification procedure will provide more practical industrial applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Recent development of protein crystallography allows us to understand protein function at atomic level. However, protein is always in motion in solution, which is of great importance to the function. Here, we show a novel method using solution X-ray scattering (SXS) and molecular dynamics (MD) simulation to characterize protein dynamics in solution. © 2011 Hie Society of Polymer Science.


Taguchi T.,Yokohama University | Oridate N.,Yokohama University
Practica Oto-Rhino-Laryngologica | Year: 2014

We reviewed our experiences with concurrent chemoradiotherapy (CCRT) treatment for patients with resectable squamous cell carcinoma (SCC) of the hypopharynx and considered the indication of CCRT for this disease. The survival rates of stage I-II hypopharyngeal SCC patients treated with radiotherapy alone were reported to be adequate. CCRT may be applied to improve the laryngeal preservation rate for stage II disease. We reported that the chemotherapy regimen and the N staging could predict the treatment outcomes of patients with advanced stage. The indication of CCRT was able to be determined by these factors. A functioning larynx could be preserved in most of the patients with hypopharyngeal SCC treated with CCRT according to our previous reports on the evaluation of laryngeal functions after CCRT.

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