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Genomic Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization
Shunichi Yoshioka, Yoshiyuki Tsukamoto, Naoki Hijiya, Chisato Nakada, Tomohisa Uchida, Keiko Matsuura, Ichiro Takeuchi, Masao Seto, Kenji Kawano, Masatsugu Moriyama
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056165
Abstract: We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.
Downregulation of SAV1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma
Keiko Matsuura, Chisato Nakada, Mizuho Mashio, Takahiro Narimatsu, Taichiro Yoshimoto, Masato Tanigawa, Yoshiyuki Tsukamoto, Naoki Hijiya, Ichiro Takeuchi, Takeo Nomura, Fuminori Sato, Hiromitsu Mimata, Masao Seto, Masatsugu Moriyama
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-523
Abstract: We performed array CGH and gene expression analysis of 8 RCC cell lines (786-O, 769-P, KMRC-1, KMRC-2, KMRC-3, KMRC-20, TUHR4TKB, and Caki-2), and expression level of mRNA was confirmed by quantitative RT-PCR (qRT-PCR) analysis. We next re-expressed SAV1 in 786-O cells, and analyzed its colony-forming activity. Then, we transfected siRNAs of SAV1 into the kidney epithelial cell line HK2 and renal proximal tubule epithelial cells (RPTECs), and analyzed their proliferation and apoptosis. Furthermore, the activity of YAP1, which is a downstream molecule of SAV1, was evaluated by western blot analysis, reporter assay and immunohistochemical analysis.We found that SAV1, a component of the Hippo pathway, is frequently downregulated in high-grade ccRCC. SAV1 is located on chromosome 14q22.1, where copy number loss had been observed in 7 of 12 high-grade ccRCCs in our previous study, suggesting that gene copy number loss is responsible for the downregulation of SAV1. Colony-forming activity by 786-O cells, which show homozygous loss of SAV1, was significantly reduced when SAV1 was re-introduced exogenously. Knockdown of SAV1 promoted proliferation of HK2 and RPTEC. Although the phosphorylation level of YAP1 was low in 786-O cells, it was elevated in SAV1-transduced 786-O cells. Furthermore, the transcriptional activity of the YAP1 and TEAD3 complex was inhibited in SAV1-transduced 786-O cells. Immunohistochemistry frequently demonstrated nuclear localization of YAP1 in ccRCC cases with SAV1 downregulation, and it was preferentially detected in high-grade ccRCC.Taken together, downregulation of SAV1 and the consequent YAP1 activation are involved in the pathogenesis of high-grade ccRCC. It is an attractive hypothesis that Hippo signaling could be candidates for new therapeutic target.Renal cell carcinoma (RCC) is histopathologically subdivided into various categories, of which clear cell renal cell carcinoma (ccRCC) is the most common subtype, accounting for 70-80% of all RC
36-Month Follow-Up Study of Post-Intervention Chronic Heart Failure Patients  [PDF]
Haruka Otsu, Michiko Moriyama
Health (Health) , 2014, DOI: 10.4236/health.2014.67075
Abstract: Aim: Although numerous studies of disease management and case management of chronic heart failure (CHF) have been carried out, length of effectiveness after program commencement has not been examined, so we examined a follow-up study at 36 months after program commencement. Methods: Participants went for follow-up visits to one Japanese clinic which specializes in internal cardiovascular medicine and they were given diagnoses of CHF. 104 outpatients participated in this study and randomized control trial was implemented. An educational program was implemented for 6 months. The data were collected at baseline, 3, 6, 9, 12 months from both intervention and control groups and at 24 and 36 months from the intervention group. Results: There was significant improvement in New York Heart Association (NYHA) in the intervention group between baseline and 36 months. Improvement in weight monitoring and activities or exercise in the intervention group continued up to 36 months. Meanwhile, sodium restricted diets and quitting smoking and/or drinking depended on individual preference and it was difficult to make improvements in these areas. Conclusions: The educational program showed promise in preventing CHF outpatients from deteriorating significantly on a long-term basis as self-monitoring of activity and weight continued significantly and there were no participants with CHF who deteriorated in the intervention group at 36 months after program commencement, although the program aimed only to provide illness and self-management knowledge. On the other hand, future work will need to compare participants in this program to a control group over an extended period of time with consideration for relieving the burden of the control group.
Electricity Generation System with Piezoelectric Element Using Acoustic Radiation Energy  [PDF]
Hiroyuki Moriyama, Yuta Yamamura
Journal of Power and Energy Engineering (JPEE) , 2018, DOI: 10.4236/jpee.2018.610001
Abstract: In this study, a circular plate that is installing a piezoelectric element at its center is adopted as energy-harvesting system and is subjected to a harmonic point force. Because this system cannot avoid the influence of its acoustic radiation, the influence is considered theoretically using the equation of plate motion taking into account its radiation impedance and is estimated by the electricity generation efficiency, which is derived from the ratio of the electric power in the electricity generation and the mechanical power supplied to the plate. As a result, the efficiency is suppressed by the acoustic radiation from the plate, so that the efficiencies are so different in whether to take into consideration the radiation impedance or not. Because those results are verified by the electricity generation experiment and radiation acoustic energy has a hopeful prospect for improving the performance of this system, mechanical-acoustic coupling is used to make the most of the acoustic energy. Therefore, a cylinder that has the above plates at both ends is also adopted as the electricity generation system and mechanical-acoustic coupling is caused between the plate vibrations and an internal sound field into the cylindrical enclosure by subjecting one side of each plate to a harmonic point force. Then, the effect of coupling is evaluated by comparing with the efficiencies in the electricity generation system of only plate. Specifically, because the radiation impedance increases with the plate thickness, i.e., with the natural frequency of the plate, it is demonstrated that the effect of coupling becomes remarkable with increasing the thickness on the electricity generation efficiency.
Lengua y etnicidad: una relación con matices
Masatsugu Matsuo
Revista CS , 2009,
Abstract: La lengua es uno de los principales factores que permiten diferenciar a un grupo étnico de otro. Sin embargo, la relación que los grupos étnicos tienen con respecto a su lengua no es invariable y el examen de casos particulares refleja una amplia gama de matices. Dada esta ambivalencia propia del tema, este artículo busca examinar qué propiedades puede asumirse que son necesarias para establecer un vínculo entre una lengua y un grupo étnico, para posteriormente explicar, por medio de algunos ejemplos, cómo dicho vínculo puede llegar a encontrarse más en una percepción compartida por el grupo que en un uso efectivo de la lengua.
Is Japanese Politics 'Un-Westminster'? Examining the Role of the PARC
YOSHIOKA, Masatsugu
Electronic Journal of Contemporary Japanese Studies , 2007,
Genomic Profiling of Submucosal-Invasive Gastric Cancer by Array-Based Comparative Genomic Hybridization
Akiko Kuroda,Yoshiyuki Tsukamoto,Lam Tung Nguyen,Tsuyoshi Noguchi,Ichiro Takeuchi,Masahiro Uchida,Tomohisa Uchida,Naoki Hijiya,Chisato Nakada,Tadayoshi Okimoto,Masaaki Kodama,Kazunari Murakami,Keiko Matsuura,Masao Seto,Hisao Ito,Toshio Fujioka,Masatsugu Moriyama
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022313
Abstract: Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic.
Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population
Tomohisa Uchida, Lam Nguyen, Akiko Takayama, Tadayoshi Okimoto, Masaaki Kodama, Kazunari Murakami, Takeshi Matsuhisa, Tuan Trinh, Long Ta, Dang Ho, Hoa Hoang, Tetsuko Kishida, Toshio Fujioka, Masatsugu Moriyama, Yoshio Yamaoka
BMC Microbiology , 2009, DOI: 10.1186/1471-2180-9-175
Abstract: The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh.Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.Helicobacter pylori is recognized to play a causative role in the pathogenesis of various gastroduodenal diseases including gastritis, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma [1-6]. However, only a minority of H. pylori-infected patients will develop severe manifestations, indicating that the clinical outcome is dependent on interactions between bacterial virulence, and host-related and environmental factors.Gastric cancer is still a significant health problem in Asian countries. More than 56% of newly diagnosed gastric cancers arise in Asia, of which 42% are reported from China and 12% from Japan (data available at http://www-dep.iarc.fr/ webcite). However the incidence of gastric cancer varies greatly, even among different regions of Asia. Based on the age-standardized incidence rate (ASR) of gastric cancer, Asian countries can be categorized as high-risk (e.g., Japan, Korea, China), intermediate
MDM2 SNP309 (rs2279744) and p53 Codon Arg72Pro (rs1042522) SNP in Cervical Carcinogenesis  [PDF]
Osamu Nunobiki, Hirohide Sawada, Masatsugu Ueda
Advances in Bioscience and Biotechnology (ABB) , 2014, DOI: 10.4236/abb.2014.57072

To investigate the association between polymorphisms (SNP) in the p53 and murine double minute 2 homolog (MDM2) promoter 309 in cervical carcinogenesis. SNP at p53 codon 72 polymorphisms and MDM2 promoter 309 (T/G) together with human papillomavirus (HPV) types were examined in a total of 187 cervical smear samples using real time PCR. 27 cases with HPV types 16 and/or 18 had significantly higher frequency of the TG + GG genotype and G allele than 56 with other types of high-risk HPV (P = 0.0136). 48 cases with HPV types 52 and/or 58 had significantly higher frequency of the TG + GG genotype and G allele than 56 with other types of high-risk HPV (P = 0.001). Our studies have demonstrated that the frequency of G allele in MDM2 promoter 309 increased from LSIL to HSIL and that there was an increased OR for G allele in HSIL cases with high-risk HPV types including 52 and 58. It is known that geographically different oncogenic HPV types 52 and 58 are more prevalent than 16 and 18 in a Japanese population.

Factor Structure of the Coping Inventory for Stressful Situations (CISS) in Japanese Workers  [PDF]
Yukihiro Takagishi, Masatsugu Sakata, Toshinori Kitamura
Psychology (PSYCH) , 2014, DOI: 10.4236/psych.2014.514172
Abstract: Different models of factor structure were proposed for the Coping Inventory for Stressful Situations (CISS) as a measure of coping style. This study confirmed psychometric properties and stability of the factor structure and differences among models for various age groups. The CISS of the Japanese version and the Hopkins Symptom Checklist (HSCL) were administered to a sample of 781 Japanese workers. Using factor analysis, three-, four-, and five-factor models were examined. Simultaneous multiple-group analysis was conducted using samples of 568 workers and 507 students. The five-factor model was more robust than the original three- and four-factor models. Reliabilities and applicability for a wide age range were confirmed. In terms of predictive validity, symptoms of somatization, obsessive-compulsiveness, interpersonal sensitivity, depression, and anxiety were positively related with Rumination coping.
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