2024/06/18 更新

写真a

サイトウ コウスケ
齋藤 孔良
SAITOH Kousuke
所属
教育研究院 医歯学系 医学系列 助教
医学部 医学科 助教
医歯学総合研究科 地域疾病制御医学専攻 国際感染医学 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2000年3月   東京医科歯科大学 )

研究キーワード

  • 老々介護

  • フレイル

経歴

  • 新潟大学   医学部 医学科   助教

    2011年10月 - 現在

  • 新潟大学   医歯学総合研究科 地域疾病制御医学専攻 国際感染医学   助教

    2011年10月 - 現在

 

論文

  • Oral self-care, pneumococcal vaccination, and pneumonia among Japanese older people, assessed with machine learning. 査読 国際誌

    Yuko Inoue, Upul Cooray, Miho Ishimaru, Kousuke Saito, Kenji Takeuchi, Katsunori Kondo, Jun Aida

    The journals of gerontology. Series A, Biological sciences and medical sciences   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Pneumonia is a leading cause of death worldwide. It is a particularly serious burden in older people, as they tend to have a weakened immune response. Identifying the role of oral self-care and pneumococcal vaccination in healthy, independent older people can aid pneumonia prevention among them. This study investigated the associations between oral self-care, pneumococcal vaccination, and pneumonia experience among independent older people. METHODS: This cross-sectional study used data from the 2016 Japan Gerontological Evaluation Study (JAGES). We used machine learning to examine the association between oral self-care and the experience of pneumonia over the previous year, stratified by pneumococcal vaccination. The covariates were sex, age, years of education, equivalent annual income, medical history of stroke, oral health status (choking, dryness, number of teeth), and smoking status. The analysis included 17,217 independent older people aged 65 and over. RESULTS: The prevalence of pneumonia experienced among those who brushed their teeth once or less per day was 4.5% and 5.3% for those with and those without pneumococcal vaccinations, respectively. In the unvaccinated group, the odds ratio of pneumonia experience for those who brushed their teeth once or less a day was 1.57 (95% CI 1.15-2.14) compared to those who brushed their teeth three or more times a day. By contrast, there was no significant association between the frequency of toothbrushing and the experience of pneumonia among people who received pneumococcal vaccination. CONCLUSION: Oral care influenced the experience of pneumonia among independent older people who did not receive pneumococcal vaccination.

    DOI: 10.1093/gerona/glad161

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  • Association of frailty with influenza and hospitalization due to influenza among independent older adults: a longitudinal study of Japan Gerontological Evaluation Study (JAGES) 査読 国際誌

    Kousuke Iwai-Saito, Koryu Sato, Jun Aida, Katsunori Kondo

    BMC Geriatrics   23 ( 1 )   249 - 249   2023年4月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: It is unknown that whether frailty is a risk factor of influenza and the hospitalization among older adults, although it has been shown that frailty was associated with poor recovery from the hospitalization among those. We examined the association of frailty with influenza and the hospitalization and the effect by sex among independent older adults. METHODS: We used the longitudinal data from the Japan Gerontological Evaluation Study (JAGES), performed in 2016 and 2019 and conducted in 28 municipalities in Japan. The target population comprised 77,103 persons aged ≥ 65 years who did not need assistance from the public long-term care insurance. Primary outcome measures were influenza and hospitalization due to influenza. Frailty was evaluated with the Kihon check list. We estimated the risk of influenza, the hospitalization, those risks by sex, and the interaction for frailty and sex using Poisson regression adjusting for covariates. RESULTS: Frailty was associated with both influenza and the hospitalization among the older adults compared with nonfrail individuals after adjusting for covariates (influenza, frail: risk ratio {RR}: 1.36, 95% confidence interval {95% CI}: 1.20 - 1.53, and prefrail: RR: 1.16, 95% CI: 1.09 - 1.23; the hospitalization, frail: RR: 3.18, 95% CI: 1.84 - 5.57, and prefrail: RR: 2.13, 95% CI: 1.44 - 3.16). Male was associated with the hospitalization, but not associated with influenza compared to female (the hospitalization: RR: 1.70, 95% CI: 1.15 - 2.52 and influenza: RR: 1.01, 95% CI: 0.95 - 1.08). The interaction for frailty and sex was significant neither in influenza nor in the hospitalization. CONCLUSION: These results suggest that frailty is a risk of influenza and the hospitalization, that risks of the hospitalization are different by sex, but that the sex difference does not cause the effect heterogeneity of frailty on the susceptibility and severity among independent older adults.

    添付ファイル: s12877-023-03979-y.pdf

    DOI: 10.1186/s12877-023-03979-y

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  • Associations of influenza and pneumococcal vaccinations with burdens of older family caregivers: The Japan Gerontological Evaluation study (JAGES) cross-sectional study. 査読

    Iwai-Saito K, Koryu Sato, Kondo K

    Vaccine   41 ( 2 )   444 - 451   2022年12月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    <h4>Background</h4>Influenza and pneumonia tend to be severe in older adults; thus, vaccination is necessary to prevent these illnesses. Vaccination is especially important for older family caregivers (OFCs) not only to prevent them from becoming ill, but also to prevent secondary infections in the family care receivers (FCRs), who are mostly frail older adults and have a higher risk of severe illness. Thus, we investigated whether caregiving burdens were associated with the vaccinations among older adults.<h4>Methods</h4>We used cross-sectional data from the Japan Gerontological Evaluation Study (JAGES), which was conducted in 64 Japanese municipalities from November 2019 to January 2020. The target population consisted of 26,177 individuals aged 65 years or older who were independent and did not need public long-term care. The primary outcome was the uptakes of either or both influenza and pneumococcal vaccinations. Multinomial logistic regressions were performed, setting those who underwent neither vaccinations as the reference group.<h4>Results</h4>Among the participants, 23.3 %, 25.8 %, 9.4 %, or 41.5 % underwent neither, only influenza, only pneumococcal, or the both vaccinations, respectively. The caregiving frequency, time length in a day, or dementia of FCR were negatively associated with influenza vaccination (caregiving almost every day: relative risk ratio {RRR}: 0.39, 95 % confident interval {95 % CI} [0.24-0.63]; caregiving almost all day: 0.44, 95 % CI: 0.23-0.85; caregiving for FCR: RRR:0.55, 95 % CI: 0.34-0.91). On the other hand, those caregiving burdens were not associated with pneumococcal only or the both vaccinations. Having a family physician mitigated all the negative effect of the caregiving burdens on the vaccinations.<h4>Conclusion</h4>Our results suggest that the caregiving burden is a barrier to influenza vaccination but not to pneumococcal vaccination and that having a physician mitigates the negative effect regardless of the burden kind.

    添付ファイル: 1-s2.0-S0264410X22014608-main.pdf

    DOI: 10.1016/j.vaccine.2022.11.047

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  • Association of functional competencies with vaccination among older adults: a JAGES cross-sectional study 査読

    Kousuke Iwai-Saito, Koryu Sato, Katsunori Kondo

    Scientific Reports   12 ( 1 )   2022年10月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    It is unknown whether higher functions in sublevels of competence other than instrumental activities of daily living (IADL) are associated with vaccinations. This study examined whether higher functions, including intellectual activity (IA) and social role (SR), were associated with vaccinations among 26,177 older adults. Older adults with incapable activities in IA and SR had increased risks for non-receipt of influenza vaccinations (IA: for one incapable task/activity: incident rate ratio (IRR) = 1.05, 95% confidence interval (CI) = 1.02–1.09; SR: for two incapable tasks: IRR = 1.12, 95% CI = 1.08–1.16). Those with incapable activities in IADL and IA had increased risks for non-receipt of pneumococcal vaccination (IADL: for two incapable tasks: IRR = 1.13, 95% CI = 1.05–1.23; IA: for two incapable tasks: IRR = 1.10, 95% CI = 1.08–1.12). Those with incapable activities in IADL, IA, and SR had increased risks for non-receipt of both of the two vaccinations (IADL: for two incapable tasks: IRR = 1.17, 95% CI = 1.03–1.33; IA: for two incapable tasks: IRR = 1.18, 95% CI = 1.11–1.25; SR: for two incapable tasks: IRR = 1.13, 95% CI = 1.07–1.20). Having a family physician mitigated associations for non-receipt, regardless of competency. Our results suggest—maintaining the higher functions are important for older adults to undergo recommended vaccinations as scheduled; also, having a family physician to promote vaccinations is beneficial even for older adults with limited functions.

    添付ファイル: s41598-022-22192-2.pdf

    DOI: 10.1038/s41598-022-22192-2

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    その他リンク: https://www.nature.com/articles/s41598-022-22192-2

  • Social capital and pneumococcal vaccination (PPSV23) in community-dwelling older Japanese: a JAGES multilevel cross-sectional study. 査読 国際誌

    Kousuke Iwai-Saito, Yugo Shobugawa, Katsunori Kondo

    BMJ open   11 ( 6 )   e043723   2021年6月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Inequalities exist between the 23-valent pneumococcal polysaccharide vaccination (PPSV23) rate in each municipality among Japanese older adults. Exploring individual-level and community-level intervenable factors is necessary to improve the vaccination rates. We examined the associations between community-level and individual-level social capital and the PPSV23 vaccination among older Japanese adults using multilevel Poisson regression analyses. DESIGN: Cross-sectional study. SETTING: We used data from the Japan Gerontological Evaluation Study, conducted between 3 October 2016 and 10 January 2017 in 631 districts, 39 municipalities and 18 prefectures. PARTICIPANTS: The target population comprised persons aged 65 years or older who are physically and cognitively independent (that is, not certified as needing long-term care). Further, 180 021 older adults from 39 Japanese municipalities were enrolled. PRIMARY OUTCOME MEASURE: The primary outcome was the PPSV23 vaccination among the Japanese older adults aged 65 years or older who did not have physical or cognitive disabilities. RESULTS: After adjusting for municipality-, community-, individual-levels effects with multiple imputation, 137 075 individuals who participated in one/more of the civic participation (participation of social groups), social cohesion (social tie), or reciprocity (mutual exchange of social support) were significantly associated with more vaccinations than those without the three social capitals among the 137 075 older adults (13.0% (95% CI 11.0% to 14.9%), 5.0% (95% CI 2.4% to 7.6%) or 33.9% (95% CI23.6% to 44.2%) increase, respectively, p>0.001 for all). The rich (≥+1 SD) community-level civic participation was significantly associated with 3.4% increase [95% CI 0.02% to 6.78%, p<0.05] of the PPSV23 vaccination among the older adults compared to those with the poor or standard one. CONCLUSIONS: Older adults with one/more of the three social capitals at the both levels received more PPSV23 vaccinations than those without those social capitals. Therefore, fostering of those social capitals may improve the inequality of the PPSV23 vaccination rate among older adults in each municipality.

    DOI: 10.1136/bmjopen-2020-043723

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  • Frailty is associated with susceptibility and severity of pneumonia in older adults (A JAGES multilevel cross-sectional study). 査読 国際誌

    Kousuke Iwai-Saito, Yugo Shobugawa, Jun Aida, Katsunori Kondo

    Scientific reports   11 ( 1 )   7966 - 7966   2021年4月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pneumonia is a leading cause of mortality among older adults worldwide. Recently, several studies reported that frailty was associated with mortality among older adults hospitalized due to respiratory infectious diseases, including pneumonia. However, it is unknown whether frailty is associated with susceptibility to and severity of pneumonia in functionally-independent community-dwelling older adults. In this study, we examined whether frailty increased the susceptibility to pneumonia and hospitalization in older adults. We used cross-sectional data from the Japan Gerontological Evaluation Study; the data was collected by using mail-based, self-reported questionnaires from 177,991 functionally-independent community-dwelling older adults aged ≥ 65 years. Our results showed that frailty was significantly associated with both occurrence of and hospitalization due to pneumonia after adjustments with covariates; (Preference ratio {PR} 1.92, 95% confidence interval {95% CI} [1.66-2.22] and PR 1.80, 95% CI [1.42-2.28], respectively, p < 0.001 for the both). Pre-frailty was associated only with the occurrence of pneumonia. Besides, the instrumental activity of daily living, physical strength, nutrition status, oral function, homeboundness, and depression status in frail older adults were associated with either or both occurrence of and hospitalization due to pneumonia. Our results suggest that frailty influenced the susceptibility to and severity of pneumonia in older adults.

    DOI: 10.1038/s41598-021-86854-3

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  • Association of pneumococcal and influenza vaccination with patient-physician communication in older adults: A nationwide cross-sectional study from the JAGES 2016. 査読

    Koryu Sato, Naoki Kondo, Chiyoe Murata, Yugo Shobugawa, Kousuke Saito, Katsunori Kondo

    Journal of epidemiology   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Increasing the coverage of vaccinations recommended by the World Health Organization in the older adult population is an urgent issue, especially in the context of avoiding co-epidemics during the current coronavirus disease 2019 crisis. The aim of this study was to examine factors associated with the quality of perceived patient-physician communication and whether this variable was associated with increased odds of vaccination. METHODS: We used cross-sectional data from the Japan Gerontological Evaluation Study conducted from October 2016 to January 2017. The participants were 22,253 physically and cognitively independent individuals aged 65 or older living in 39 municipalities in Japan. Multilevel logit models were used to estimate the odds of vaccination. RESULTS: Among the participants, 40.0% and 58.8% had received pneumococcal and influenza vaccinations as per the recommended schedule, respectively. People with low educational levels were more likely to have a family physician but rate their experience in asking questions lower than those with higher educational levels. Having a family physician and high rating for physicians' listening attitude were positively associated with increased odds of pneumococcal and influenza vaccinations. High rating for patients' questioning attitude and shared decision-making, compared to an ambiguous attitude toward medical decision-making, were positively associated with increased odds of pneumococcal vaccination. CONCLUSION: The results suggest that promotion of having a family physician, better patient-physician communication, and shared decision-making may encourage older adults to undergo recommended vaccinations.

    DOI: 10.2188/jea.JE20200505

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  • Development of cycling probe based real-time PCR methodology for influenza A viruses possessing the PA/I38T amino acid substitution associated with reduced baloxavir susceptibility. 査読 国際誌

    Hidekazu Osada, Irina Chon, Wint Wint Phyu, Keita Wagatsuma, Nobuo Nagata, Takashi Kawashima, Isamu Sato, Tadashi Saito, Naoki Kodo, Hironori Masaki, Norichika Asoh, Yoshiko Tsuchihashi, Yutaka Shirahige, Yasuhiko Ono, Yasushi Shimada, Hirotsune Hamabata, Kousuke Saito, Reiko Saito

    Antiviral research   188   105036 - 105036   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Baloxavir marboxil has been used for influenza treatment since March 2018 in Japan. After baloxavir treatment, the most frequently detected substitution is Ile38Thr in polymerase acidic protein (PA/I38T), and this substitution reduces baloxavir susceptibility in influenza A viruses. To rapidly investigate the frequency of PA/I38T in influenza A (H1N1)pdm09 and A (H3N2) viruses in clinical samples, we established a rapid real-time system to detect single nucleotide polymorphisms in PA, using cycling probe real-time PCR. We designed two sets of probes that were labeled with either 6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX) to identify PA/I38 (wild type strain) or PA/I38T, respectively. The established cycling probe real-time PCR system showed a dynamic linear range of 101 to 106 copies with high sensitivity in plasmid DNA controls. This real-time PCR system discriminated between PA/I38T and wild type viruses well. During the 2018/19 season, 377 influenza A-positive clinical samples were collected in Japan before antiviral treatment. Using our cycling probe real-time PCR system, we detected no (0/129, 0.0%) influenza A (H1N1)pdm09 viruses with PA/I38T substitutions and four A (H3N2) (4/229, 1.7%) with PA/I38T substitution prior to treatment. In addition, we found PA/I38T variant in siblings who did not received baloxavir treatment during an infection caused by A (H3N2) that afflicted the entire family. Although human-to-human transmission of PA/I38T variant may have occurred in a closed environment, the prevalence of this variant in influenza A viruses was still limited. Our cycling probe-PCR system is thus useful for antiviral surveillance of influenza A viruses possessing PA/I38T.

    DOI: 10.1016/j.antiviral.2021.105036

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  • MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia. 査読

    Kozakai T, Takahashi M, Higuchi M, Hara T, Saito K, Tanaka Y, Masuko M, Takizawa J, Sone H, Fujii M

    International journal of hematology   107 ( 3 )   337 - 344   2018年3月

  • USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells 査読

    Masaya Higuchi, Hiroki Kawamura, Hideaki Matsuki, Toshifumi Hara, Masahiko Takahashi, Suguru Saito, Kousuke Saito, Shuying Jiang, Makoto Naito, Hiroshi Kiyonari, Masahiro Fujii

    STEM CELL REPORTS   7 ( 6 )   1116 - 1129   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Self-renewal, replication, and differentiation of hematopoietic stem cells (HSCs) are regulated by cytokines produced by niche cells in fetal liver and bone marrow. HSCs must overcome stresses induced by cytokine deprivation during normal development. In this study, we found that ubiquitin-specific peptidase 10 (USP10) is a crucial deubiquitinase for mouse hematopoiesis. All USP10 knockout (KO) mice died within 1 year because of bone marrow failure with pancytopenia. Bone marrow failure in these USP10-KO mice was associated with remarkable reductions of long-term HSCs (LT-HSCs) in bone marrow and fetal liver. Such USP10-KO fetal liver exhibited enhanced apoptosis of hematopoietic stem/progenitor cells (HSPCs) including LT-HSCs but not of lineage-committed progenitor cells. Transplantation of USP10-competent bone marrow cells into USP10-KO mice reconstituted multilineage hematopoiesis. These results suggest that USP10 is an essential deubiquitinase in hematopoiesis and functions by inhibiting apoptosis of HSPCs including LT-HSCs.

    DOI: 10.1016/j.stemcr.2016.11.003

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  • The effects of neuraminidase inhibitors on the release of oseltamivir-sensitive and oseltamivir-resistant influenza viruses from primary cultures of human tracheal epithelium 査読

    Mutsuo Yamaya, Lusamba Nadine, Hiroshi Kubo, Kousuke Saito, Reiko Saito, Hidekazu Nishimura

    Journal of Medical Virology   87 ( 1 )   25 - 34   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:John Wiley and Sons Inc.  

    Defining the effects of neuraminidase inhibitors on influenza virus infection may provide important information for the treatment of patients. The effects of neuraminidase inhibitors have been examined using various methods, including viral release from kidney cells. However, the effects of neuraminidase inhibitors on viral release from primary cultures of human tracheal epithelial cells, which retain functions of the original tissues, have not been studied. The effects of neuraminidase inhibitors on the replication of the pandemic influenza virus [A/Sendai-H/N0633/2009 (H1N1) pdm09] and the seasonal influenza virus [A/Sendai-H/216/2009 (H1N1)] that was isolated during the 2008-2009 season were examined. The virus stocks were generated by infecting tracheal cells with the pandemic or seasonal influenza virus. Four types of inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) reduced pandemic viral titers and concentrations of the cytokines interleukin-6 and tumor necrosis factor-α in supernatants and viral RNA in cells. However, oseltamivir did not reduce seasonal viral titers, cytokine concentrations and viral RNA, and the 50% inhibitory concentration (IC50) of oseltamivir for neuraminidase activity in the seasonal virus was 300-fold higher than that observed for the pandemic influenza virus. The seasonal influenza virus had an oseltamivir-resistant genotype. The magnitude of the IC50 values of the neuraminidase inhibitors for the seasonal influenza virus was inversely related to the magnitude of the inhibitory effects on viral release. These methods for measuring the release of virus and inflammatory cytokines from primary cultures of human tracheal epithelium may provide useful information regarding the effects of neuraminidase inhibitors on influenza viruses.

    DOI: 10.1002/jmv.23974

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  • The effects of neuraminidase inhibitors on the release of oseltamivir-sensitive and oseltamivir-resistant influenza viruses from primary cultures of human tracheal epithelium. 査読

    Yamaya M, Nadine L, Kubo H, Saito K, Saito R, Nishimura H

    Journal of medical virology   87 ( 1 )   25 - 34   2015年1月

  • Characterization of human influenza viruses in lebanon during 2010-2011 and 2011-2012 post-pandemic seasons 査読

    Hassan Zaraket, Clyde Dapat, Soha Ghanem, Zainab Ali, Mireille Lteif, Hiroki Kondo, Isolde C. Dapat, Kousuke Saito, Ghazi Kayali, Hiroshi Suzuki, Ghassan Dbaibo, Reiko Saito

    Intervirology   57 ( 6 )   344 - 352   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:S. Karger AG  

    Objective: To genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in Lebanon.
    Methods: Influenza virus was isolated from nasopharyngeal swabs that were obtained from patients with influenza-like illness during 2010-2012 and further analyzed both phenotypically and genotypically.
    Results: During the 2010-2011 season, both 2009 pandemic H1N1 (H1N1p) and B viruses co-circulated with equal prevalence, while the H3N2 virus predominated during the 2011-2012 season. All H3N2 and H1N1 viruses were resistant to amantadine. Importantly, all viruses of the influenza A and B types were susceptible to the neuraminidase (NA) inhibitors oseltamivir, zanamivir, peramivir, and laninamivir. Nonetheless, all 2011-2012 H1N1p isolates had three mutations (V241I, N369K, and N386S) in the NA gene that were suggested to be permissive of the H275Y mutation, which confers resistance to oseltamivir. We also detected one H1N1p virus during the 2010-2011 season with a 4-fold decrease in susceptibility to oseltamivir due to an NA-S247N mutation. This isolate was phylogenetically distinct from other H1N1p viruses that were isolated in other regions.
    Conclusions: Influenza A viruses with reduced susceptibility to oseltamivir and mutations permissive for acquiring NA resistance-conferring mutation with minimal burden on their fitness were isolated in Lebanon.

    DOI: 10.1159/000365758

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  • 耐性ウイルスはどのようにしてみつけるのでしょうか

    齋藤孔良

    インフルエンザ   15 ( 2 )   92 - 92   2014年4月

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  • 【耐性病原体up-to-date?耐性メカニズムから治療戦略まで?】 耐性病原体 ウイルス オセルタミビル耐性インフルエンザ

    齋藤孔良, 齋藤玲子

    化学療法の領域   30 ( 増刊号 )   1070 - 1079   2014年4月

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  • ノイラミニダーゼ阻害薬の種類によって耐性ウイルスの出やすさに違いがあるのですか

    齋藤孔良

    インフルエンザ   15 ( 2 )   90 - 91   2014年4月

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  • Effectiveness of trivalent influenza vaccine among children in two consecutive seasons in a community in Japan. 査読

    Tsubasa Suzuki, Yasuhiko Ono, Hidenori Maeda, Yoshiki Tsujimoto, Yugo Shobugawa, Clyde Dapat, Mohd Rohaizat Hassan, Chihiro Yokota, Hiroki Kondo, Isolde C Dapat, Kousuke Saito, Reiko Saito

    The Tohoku journal of experimental medicine   232 ( 2 )   97 - 104   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Influenza vaccination is considered the single most important medical intervention for the prevention of influenza. The dose of trivalent influenza vaccine in children was increased almost double since 2011/12 season in Japan. We estimated the influenza vaccine effectiveness for children 1-11 years of age using rapid test kits in Isahaya City, involving 28,884 children-years, over two consecutive influenza seasons (2011/12 and 2012/13). Children were divided into two groups, vaccinated and unvaccinated, according to their vaccination record, which was obtained from an influenza registration program organized by the Isahaya Medical Association for all pediatric facilities in the city. There were 14,562 and 14,282 children aged from 1-11 years in the city in 2011 and 2012 respectively. In the 2011/12 season, the overall vaccine effectiveness in children from 1-11 years of age, against influenza A and B were 23% [95% confidence interval (CI): 14%-31%] and 20% [95% CI: 8%-31%], respectively. In the 2012/13 season, vaccine effectiveness against influenza A and B was 13% (95% CI: 4%-20%) and 9% (95% CI: -4%-21%), respectively. The vaccine effectiveness was estimated using the rapid diagnosis test kits. Age-stratified estimation showed that vaccine effectiveness was superior in younger children over both seasons and for both virus types. In conclusion, the trivalent influenza vaccine has a significant protective effect for children 1-11 years of age against influenza A and B infection in the 2011/12 season and against influenza A infection in the 2012/13 season in a community in Japan.

    DOI: 10.1620/tjem.232.97

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  • 耐性ウイルスの基準について教えてください

    齋藤 孔良, 高下恵美

    インフルエンザ   15 ( 1 )   30 - 30   2014年1月

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  • Characterization of Human Influenza Viruses in Lebanon during 2010-2011 and 2011-2012 Post-Pandemic Seasons 査読

    Hassan Zaraket, Clyde Dapat, Soha Ghanem, Zainab Ali, Mireille Lteif, Hiroki Kondo, Isolde C. Dapat, Kousuke Saito, Ghazi Kayali, Hiroshi Suzuki, Ghassan Dbaibo, Reiko Saito

    INTERVIROLOGY   57 ( 6 )   344 - 352   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Objective: To genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in Lebanon. Methods: Influenza virus was isolated from nasopharyngeal swabs that were obtained from patients with influenza-like illness during 2010-2012 and further analyzed both phenotypically and genotypically. Results: During the 2010-2011 season, both 2009 pandemic H1N1 (H1N1p) and B viruses co-circulated with equal prevalence, while the H3N2 virus predominated during the 2011-2012 season. All H3N2 and H1N1 viruses were resistant to amantadine. Importantly, all viruses of the influenza A and B types were susceptible to the neuraminidase (NA) inhibitors oseltamivir, zanamivir, peramivir, and laninamivir. Nonetheless, all 2011-2012 H1N1p isolates had three mutations (V241I, N369K, and N386S) in the NA gene that were suggested to be permissive of the H275Y mutation, which confers resistance to oseltamivir. We also detected one H1N1p virus during the 2010-2011 season with a 4-fold decrease in susceptibility to oseltamivir due to an NA-S247N mutation. This isolate was phylogenetically distinct from other H1N1p viruses that were isolated in other regions. Conclusions: Influenza A viruses with reduced susceptibility to oseltamivir and mutations permissive for acquiring NA resistance-conferring mutation with minimal burden on their fitness were isolated in Lebanon. (C) 2014 S. Karger AG, Basel.

    DOI: 10.1159/000365758

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  • Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan. 査読

    Dapat C, Kondo H, Dapat IC, Baranovich T, Suzuki Y, Shobugawa Y, Saito K, Saito R, Suzuki H

    Antiviral research   99 ( 3 )   261 - 269   2013年9月

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  • Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan. 査読 国際誌

    Clyde Dapat, Hiroki Kondo, Isolde C Dapat, Tatiana Baranovich, Yasushi Suzuki, Yugo Shobugawa, Kousuke Saito, Reiko Saito, Hiroshi Suzuki

    Antiviral research   99 ( 3 )   261 - 9   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Two new influenza virus neuraminidase inhibitors (NAIs), peramivir and laninamivir, were approved in 2010 which resulted to four NAIs that were used during the 2010-2011 influenza season in Japan. This study aims to monitor the susceptibility of influenza virus isolates in 2009-2010 and 2010-2011 influenza seasons in Japan to the four NAIs using the fluorescence-based 50% inhibitory concentration (IC₅₀) method. Outliers were identified using box-and-whisker plot analysis and full NA gene sequencing was performed to determine the mutations that are associated with reduction of susceptibility to NAIs. A total of 117 influenza A(H1N1)pdm09, 59 A(H3N2), and 18 type B viruses were tested before NAI treatment and eight A(H1N1)pdm09 and 1 type B viruses were examined from patients after NAI treatment in the two seasons. NA inhibition assay showed type A influenza viruses were more susceptible to NAIs than type B viruses. The peramivir and laninamivir IC₅₀ values of both type A and B viruses were significantly lower than the oseltamivir and zanamivir IC₅₀ values. Among influenza A(H1N1)pdm09 viruses, the prevalence of H274Y viruses increased from 0% in the 2009-2010 season to 3% in the 2010-2011 season. These H274Y viruses were resistant to oseltamivir and peramivir with 200-300 fold increase in IC₅₀ values but remained sensitive to zanamivir and laninamivir. Other mutations in NA, such as I222T and M241I were identified among the outliers. Among influenza A(H3N2) viruses, two outliers were identified with D151G and T148I mutations, which exhibited a reduction in susceptibility to oseltamivir and zanamivir, respectively. Among type B viruses, no outliers were identified to the four NAIs. For paired samples that were collected before and after drug treatment, three (3/11; 27.3%) H274Y viruses were identified among A(H1N1)pdm09 viruses after oseltamivir treatment but no outliers were found in the laninamivir-treatment group (n=3). Despite widespread use of NAIs in Japan, the prevalence of NAI-resistant influenza viruses is still low.

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  • 耐性インフルエンザウイルスの動向 (特集 新型インフルエンザは再びおこるか)

    齋藤 玲子, 齋藤 孔良

    化学療法の領域   29 ( 増刊号 )   1018 - 1026   2013年4月

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  • 【新興・再興感染症up to date〜Emerging and re-emerging infectious disease〜】 ウイルス感染症 RSウイルス感染症

    齋藤 孔良, 菖蒲川 由郷, 佐野 康子, 齋藤 玲子, 鈴木 宏

    化学療法の領域 (Antibiotics & Chemotherapy)   29 ( 増刊号 )   1018 - 1026   2013年4月

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  • インフルエンザ・ワクチンについて (ワクチンをめぐる最近の話題)

    齋藤 孔良, 齋藤 玲子

    順天堂醫事雑誌   59 ( 1 )   41 - 48   2013年2月

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    記述言語:日本語   出版者・発行元:順天堂医学会  

    DOI: 10.14789/pjmj.59.41

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    その他リンク: http://search.jamas.or.jp/link/ui/2014071034

  • Clinical effectiveness of neuraminidase inhibitors--oseltamivir, zanamivir, laninamivir, and peramivir--for treatment of influenza A(H3N2) and A(H1N1)pdm09 infection: an observational study in the 2010-2011 influenza season in Japan. 査読

    Shobugawa Y, Saito R, Sato I, Kawashima T, Dapat C, Dapat IC, Kondo H, Suzuki Y, Saito K, Suzuki H

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   18 ( 6 )   858 - 864   2012年12月

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    出版者・発行元:Elsevier {BV}  

    DOI: 10.1007/s10156-012-0428-1

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  • Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells. 査読

    Kousuke Saito, Mineki Saito, Naoko Taniura, Takako Okuwa, Yoshiro Ohara

    Virology   403 ( 2 )   173-180   2010年8月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.virol.2010.04.018

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  • Hepatitis C Virus Core Protein Interacts With Fibrinogen-beta and Attenuates Cytokine Stimulated Acute-Phase Response 査読

    Malika Ait-Goughoulte, Arup Banerjee, Keith Meyer, Budhaditya Mazumdar, Kousuke Saito, Ratna B. Ray, Ranjit Ray

    HEPATOLOGY   51 ( 5 )   1505 - 1513   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Fibrinogen-beta (FBG-beta), an important acute-phase protein (APP), is generated by the liver as a target for inflammatory mediators. Here we identified FBG-beta as a hepatitis C virus (HCV) core interacting protein by screening a human liver complementary DNA (cDNA) library using mammalian two-hybrid analysis. An association between FBG-beta and HCV core protein was verified by confocal microscopy and coimmunoprecipitation from the transfected human hepatocyte (Huh-7) cell line. HCV core or genomic RNA transfected Huh-7 cells modestly increased FBG-beta protein expression when compared to the basal level in control hepatocytes. Transfection of HCV core or full-length (FL) gene into Huh-7 cells up-regulated basal FBG-beta promoter activity. Exogenous addition of IL-6 stimulates FBG-beta promoter activity in hepatocytes. However, ectopic expression of HCV core or FL in hepatocytes inhibited IL-6-stimulated FBG-beta promoter activation. Inhibition of endogenous FBG-beta expression following introduction of small interfering RNA (siRNA) into cells displayed a gain of function of promoter regulation by HCV core protein. Further studies suggested that HCV core gene expression in stable transfectants of Huh-7 cells resulted in a basal up-regulation of FBG-beta and other APPs. However, treatment with cytokines, interleukin-6 (IL-6), or tumor necrosis factor-alpha repressed FBG-beta and other acute-phase response (APR) genes. Conclusion: Our results reveal that the core/FBG-beta interaction may act as a regulatory feedback, allowing repression of IL-6-stimulated APR genes. Together, these data suggested a network of interactions between HCV core and the hepatic APR genes, and may contribute to impaired innate immunity for viral persistence. (HEPATOLOGY 2010;51:1505-1513.)

    DOI: 10.1002/hep.23502

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  • Analysis of the mechanism by which BALB/c mice having prior immunization with nucleocapsid protein of SARS-CoV develop severe pneumonia after SARS-CoV infection. 国際誌

    Fumihiko Yasui, Chieko Kai, Kousuke Saito, Shingo Inoue, Misako Yoneda, Kouichi Morita, Kyosuke Mizuno, Michinori Kohara

    Procedia in vaccinology   2 ( 1 )   44 - 50   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The precise mechanism of severe acute respiratory syndrome (SARS), which is caused by SARS-associated coronavirus (SARS-CoV), is still unclear. We generated recombinant vaccinia virus (rVV) LC16m8 strain which simultaneously expresses four structural proteins of SARS-CoV, including nucleocapsid (N), membrane (M), envelop (E), spike (S) proteins (rVV-NMES) and reported that old BALB/c mice having prior immunization with rVV-NMES develop severe pneumonia similar to those of control mice though rVV-NMES-immunized mice showed lower pulmonary viral titer than in the control mice. Furthermore, we determined which SARS-CoV structural protein for the prior rVV-immunization is responsible for the severe pneumonia after the SARS-CoV infection as observed in the rVV-NMES-immunized mice. Old BALB/c mice were inoculated intradermally with rVV that expressed each structural proteins of SARS-CoV (rVV-N, -M, -E, or -S) with or without rVV-S and then infected intranasally with SARS-CoV more than 4 weeks later. At 9 days after SARS-CoV infection, the rVV-N-immunized mice show more severe pneumonia than in other groups. Furthermore, significant up-regulation of Th1 (IL-2)- and Th2 (IL-4 and IL-5)-bias cytokines and down-regulation of anti-inflammatory cytokine (IL-10 and TGF-β) were observed in rVV-N-immunized mice, resulting in the intensive infiltration of immunocompetent cells into the lung. In contrast, rVV-S-immunized mice showed only low pulmonary viral tier and slight pneumonia. However, the mice having co-immunization with both rVV-N and rVV-S showed severe pneumonia though their pulmonary viral titer was low. These results suggest that an excessive host immune response against the N protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.

    DOI: 10.1016/j.provac.2010.03.009

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  • ウイルス性脱髄におけるアポトーシスの役割(第2報)

    大原 義朗, 大桑 孝子, 谷浦 直子, 齊藤 峰輝, 斎藤 孔良

    臨床神経学   49 ( 12 )   1191 - 1191   2009年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • HAM、ATL治療標的候補分子Bcl-3のHTLV-1感染による高発現機構の解析と制御法の検討

    齊藤 峰輝, 斎藤 孔良, 谷浦 直子, 大桑 孝子, 大原 義朗

    臨床神経学   49 ( 12 )   1068 - 1068   2009年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • Hepatitis C Virus Core Protein and Cellular Protein HAX-1 Promote 5-Fluorouracil-Mediated Hepatocyte Growth Inhibition 査読

    Arup Banerjee, Kousuke Saito, Keith Meyer, Sutapa Banerjee, Malika Ait-Goughoulte, Ratna B. Ray, Ranjit Ray

    JOURNAL OF VIROLOGY   83 ( 19 )   9663 - 9671   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Hepatitis C virus (HCV) often causes chronic infection and may lead to hepatocellular carcinoma (HCC). We have shown previously that HCV core protein has pleiotropic functions, including transcriptional regulation of a number of cellular genes, although the mechanism for gene regulation remains unclear. In this study, a mammalian two-hybrid screen identified a novel binding partner, HS1-associated protein X-1 (HAX-1), for HCV core protein from a human liver cDNA library. An association between HAX-1 and HCV core protein was further verified by confocal microscopy and coimmunoprecipitation in HepG2 cells expressing HCV core or full-length (FL) gene. Both HCV core protein and a chemotherapeutic agent for HCC, 5-flouorouracil (5-FU), are known to modulate p53. We examined here whether an association between core and HAX-1 has any functional relevance to p53 modulation in 5-FU-treated cells. For this, the role of HAX-1 on 5-FU treatment was examined in HepG2 cells expressing HCV core or FL gene using cell proliferation, p53 expression, and caspase activation analysis. Cells expressing HCV-core or FL gene were more susceptible to 5-FU-induced growth inhibition than control cells, whereas cell survival was enhanced after suppression of HAX-1 by small interfering RNA. Further, 5-FU-mediated p53 expression was reduced with concurrent HAX-1 suppression in core-or polyprotein-expressing cells compared to control HepG2 cells, and caspase-2 and -7 activities were diminished. On the other hand, HCV core protein did not play a detectable role in 5-FU-mediated caspase-7 activation in the absence of functional p53 in Hep3B or Huh-7 cells. These observations underscore an association between HCV core and HAX-1, which promotes 5-FU mediated p53-dependent caspase-7 activation and hepatocyte growth inhibition.

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  • Different subcellular localization of Theiler's murine encephalomyelitis virus leader proteins of GDVII and DA strains in BHK-21 cells. 査読 国際誌

    Naoko Taniura, Mineki Saito, Takako Okuwa, Kousuke Saito, Yoshiro Ohara

    Journal of virology   83 ( 13 )   6624 - 30   2009年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The highly virulent GDVII strain of Theiler's murine encephalomyelitis virus causes acute and fatal encephalomyelitis, whereas the DA strain causes mild encephalomyelitis followed by a chronic inflammatory demyelinating disease with virus persistence. The differences in the amino acid sequences of the leader protein (L) of the DA and GDVII strains are greater than those for any other viral protein. We examined the subcellular distribution of DA L and GDVII L tagged with the FLAG epitope in BHK-21 cells. Wild-type GDVII L was localized predominantly in the cytoplasm, whereas wild-type DA L showed a nucleocytoplasmic distribution. A series of the L mutant experiments demonstrated that the zinc finger domain, acidic domain, and C-terminal region of L were necessary for the nuclear accumulation of DA L. A GDVII L mutant with a deletion of the serine/threonine (S/T)-rich domain showed a nucleocytoplasmic distribution, in contrast to the predominant cytoplasmic distribution of wild-type GDVII L. A chimeric DA/GDVII L, D/G, which encodes the N region of DA L including the zinc finger domain and acidic domain, followed by the GDVII L sequence including the S/T-rich domain, was distributed exclusively throughout the cytoplasm but not in the nucleus, as observed with wild-type GDVII L. Another chimeric L, G/D (which is the converse of the D/G construct), accumulated in the nucleus as well as the cytoplasm, as was observed for wild-type DA L. The findings suggest that the differential distribution of DA L and GDVII L is determined primarily by the S/T-rich domain. The S/T-rich domain may be important for the viral activity through the regulation of the subcellular distribution of L.

    DOI: 10.1128/JVI.02385-08

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  • ウイルス性脱髄におけるアポトーシスの果たす役割

    大桑 孝子, 谷浦 直子, 齊藤 峰輝, 斎藤 孔良, 大原 義朗

    神経免疫学   17 ( 1 )   112 - 112   2009年3月

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    記述言語:日本語   出版者・発行元:(一社)日本神経免疫学会  

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  • HTLV-1感染T細胞の機能異常をもたらす恒常的なBcl-3高発現機構の解析とその制御法の検討

    斎藤 孔良, 齊藤 峰輝, 谷浦 直子, 大桑 孝子, 大原 義朗

    神経免疫学   17 ( 1 )   117 - 117   2009年3月

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    記述言語:日本語   出版者・発行元:(一社)日本神経免疫学会  

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  • In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) 査読

    Mineki Saito, Toshio Matsuzaki, Yorifumi Satou, Jun-ichirou Yasunaga, Kousuke Saito, Kimiyoshi Arimura, Masao Matsuoka, Yoshiro Ohara

    RETROVIROLOGY   6   19   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Recently, human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL) development. However, there have been no reports on the role of HBZ in patients with HTLV-1 associated inflammatory diseases.
    Results: We quantified the HBZ and tax mRNA expression levels in peripheral blood from 56 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 10 ATL patients, 38 healthy asymptomatic carriers (HCs) and 20 normal uninfected controls, as well as human leukemic T-cell lines and HTLV-1-infected T-cell lines, and the data were correlated with clinical parameters. The spliced HBZ gene was transcribed in all HTLV-1-infected individuals examined, whereas tax mRNA was not transcribed in significant numbers of subjects in the same groups. Although the amount of HBZ mRNA expression was highest in ATL, medium in HAM/TSP, and lowest in HCs, with statistical significance, neither tax nor the HBZ mRNA expression per HTLV-1-infected cell differed significantly between each clinical group. The HTLV-1 HBZ, but not tax mRNA load, positively correlated with disease severity and with neopterin concentration in the cerebrospinal fluid of HAM/TSP patients. Furthermore, HBZ mRNA expression per HTLV-1-infected cell was decreased after successful immunomodulatory treatment for HAM/TSP.
    Conclusion: These findings suggest that in vivo expression of HBZ plays a role in HAM/TSP pathogenesis.

    DOI: 10.1186/1742-4690-6-19

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  • ウイルス性脱髄におけるアポトーシスの役割

    大原 義朗, 大桑 孝子, 谷浦 直子, 齊藤 峰輝, 斎藤 孔良

    臨床神経学   48 ( 12 )   1097 - 1097   2008年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • タイラーウイルスDA株のマクロファージ感染・増殖に寄与するLタンパク内領域の検索

    野尻 正史, 淺倉 慶子, 谷浦 直子, 大桑 孝子, 斎藤 孔良, 齊藤 峰輝, 大原 義朗

    金沢医科大学雑誌   33 ( 2 )   101 - 102   2008年8月

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    記述言語:日本語   出版者・発行元:金沢医科大学医学会  

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  • Hepatitis C virus inhibits cell surface expression of HLA-DR, prevents dendritic cell maturation, and induces interleukin-10 production 査読

    Kousuke Saito, Malika Ait-Goughoulte, Steven M. Truscott, Keith Meyer, Azra Blazevic, Getahun Abate, Ratna B. Ray, Daniel F. Hoft, Ranjit Ray

    JOURNAL OF VIROLOGY   82 ( 7 )   3320 - 3328   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Hepatitis C virus (HCV) chronic infection is characterized by low-level or undetectable cellular immune responses against HCV antigens. HCV proteins have been shown to affect various intracellular events and modulate immune responses, although the precise mechanisms used to mediate these effects are not fully understood. In this study, we have examined the effect of HCV proteins on the modulation of major histocompatibility complex (MHC) class II expression and other functions important for antigen presentation in humans. Expression of an HCV1-2962 genomic clone (HCV-FL) in human fibrosarcoma cells (HT1080) inhibited gamma interferon (IFN-gamma)-induced upregulation of human leukocyte antigen-DR (HLA-DR) cell surface expression. Furthermore, inhibition of promoter activities of MHC class II transactivator (CIITA), IFN-gamma-activated site (GAS), and HLA-DR was observed in IFN-gamma-inducible HT1080 cells expressing HCV-FL by in vitro reporter assays. Exposure of human monocyte-derived dendritic cells (DCs) to cell culture-grown HCV (HCVcc) genotype la (clone H77) or 2a (clone JFH1) significantly inhibited DC maturation and was associated with the production of IL-10. Furthermore, DCs exposed to HCVcc were impaired in their functional ability to stimulate antigen-specific CD4-positive (CD4(+)) and CD8(+) T-cell responses. Taken together, our results indicated that HCV can have direct and/or indirect inhibitory effects on antigen-presenting cells, resulting in reduction of antigen-specific T-cell activation. These effects may account for or contribute to the low overall level of immunogenicity of HCV observed in chronically infected patients.

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  • 中枢神経系脱髄疾患 EAE動物モデルからの解析 タイラーウイルス両亜群非構成蛋白Lの細胞内局在の解析

    谷浦 直子, 齊藤 峰輝, 大桑 孝子, 斎藤 孔良, 大原 義朗

    神経免疫学   16 ( 1 )   42 - 42   2008年4月

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  • Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance. 査読 国際誌

    Sutapa Banerjee, Kousuke Saito, Malika Ait-Goughoulte, Keith Meyer, Ratna B Ray, Ranjit Ray

    Journal of virology   82 ( 6 )   2606 - 12   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Chronic hepatitis C virus (HCV) infection has a significantly increased prevalence of type 2 diabetes mellitus (T2DM). Insulin resistance is a critical component of T2DM pathogenesis. Several mechanisms are likely to be involved in the pathogenesis of HCV-related insulin resistance. Since we and others have previously observed that HCV core protein activates c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase, we examined the contribution of these pathways to insulin resistance in hepatocytes. Our experimental findings suggest that HCV core protein alone or in the presence of other viral proteins increases Ser(312) phosphorylation of the insulin receptor substrate-1 (IRS-1). Hepatocytes infected with cell culture-grown HCV genotype 1a or 2a displayed a significant increase in the Ser(473) phosphorylation status of the Ser/Thr kinase protein kinase B (Akt/PKB), while Thr(308) phosphorylation was not significantly altered. HCV core protein-mediated Ser(312) phosphorylation of IRS-1 was inhibited by JNK (SP600125) and phosphatidylinositol-3 kinase (LY294002) inhibitors. A functional assay also suggested that hepatocytes expressing HCV core protein alone or infected with cell culture-grown HCV exhibited a suppression of 2-deoxy-d-[(3)H]glucose uptake. Inhibition of the JNK signaling pathway significantly restored glucose uptake despite HCV core expression in hepatocytes. Taken together, our results demonstrated that HCV core protein increases IRS-1 phosphorylation at Ser(312) which may contribute in part to the mechanism of insulin resistance.

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  • タイラーウイルスのマクロファージ内増殖におけるL及びL*蛋白の役割

    淺倉 慶子, 谷浦 直子, 大桑 孝子, 斎藤 孔良, 齊藤 峰輝, 大原 義朗

    金沢医科大学雑誌   32 ( 2 )   125 - 126   2007年8月

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    記述言語:日本語   出版者・発行元:金沢医科大学医学会  

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  • Sulfated homologues of heparin inhibit hepatitis C virus entry into mammalian cells 査読

    Arnab Basu, Tatsuo Kanda, Aster Beyene, Kousuke Saito, Keith Meyer, Ranjit Ray

    JOURNAL OF VIROLOGY   81 ( 8 )   3933 - 3941   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    The mechanism of entry of hepatitis C virus (HCV) through interactions between the envelope glycoproteins and specific cell surface receptors remains unclear at this time. We have previously shown with the vesicular stomatitis virus (VSV)/HCV pseudotype model that the hypervariable region I of the HCV E2 envelope glycoprotein helps in binding with glycosaminoglycans present on the cell surface. In this study, we have examined the binding of HCV envelope glycoproteins with chemically modified derivatives of heparin. Furthermore, we have determined the functional relevance of the interaction of heparin derivatives with HCV envelope glycoproteins for infectivity by using a human immunodeficiency virus (HIV)/HCV pseudotype, a VSV/HCV pseudotype, and cell culture-grown HCV genotype 1a. Taken together, our results suggest that the HCV envelope glycoproteins rely upon O-sulfated esters of a heparin homologue to facilitate entry into mammalian cells.

    DOI: 10.1128/JVI.02622-06

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  • Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance 査読

    Banerjee, S, Saito, K, Ait-Goughoulte, M, Meyer, K, Ray, R. B, Ray, R

    Journal of virology   82 ( 6 )   2606 - 2012   2007年

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  • Stellate cell apoptosis by a soluble mediator from immortalized human hepatocytes 査読

    Arnab Basu, Kousuke Saito, Keith Meyer, Ratna B. Ray, Scott L. Friedman, Yie-Hwa Chang, Ranjit Ray

    APOPTOSIS   11 ( 8 )   1391 - 1400   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Activated hepatic stellate cells (HSCs) are the major source of extracellular matrix in fibrosis and cirrhosis. In this study, we have investigated the role of hepatitis C virus (HCV) core protein induced immortalized human hepatocytes (IHH) on HSC growth. Preferential growth of IHH and apoptosis of activated human hepatic stellate cells (LX2) were observed upon coculture of these two cell types in a dual chamber or in the presence of conditioned medium (CM) from IHH. CM did not display a growth inhibitory role on other hepatic (Huh-7, HepG2, Hep3B and THLE) and non-hepatic (HeLa, MCF-7, and BHK) epithelial cells, indicating that the soluble mediator from IHH does not have a generalized effect on cell lines examined in our study. Further studies suggested that CM from IHH increased the expression of TRAIL receptors on LX2 cell surface, and induced apoptosis by a caspase dependent mechanism. Peptide mass fingerprinting of the purified soluble mediator from CM suggested that gelsolin fragments may play a role in apoptosis of LX2 cells. Taken together, our results suggested that a soluble mediator secreted from immortalized human hepatocytes plays an important role in hepatic stellate cell growth regulation.

    DOI: 10.1007/s10495-006-8312-z

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  • Microarray analyses and molecular profiling of Stat3 signaling pathway induced by hepatitis C virus core protein in human hepatocytes 査読

    A Basu, K Meyer, KK Lai, K Saito, AM Di Bisceglie, LE Grosso, RB Ray, R Ray

    VIROLOGY   349 ( 2 )   347 - 358   2006年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Hepatitis C virus (HCV) infection is a major contributor to the development of end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC). We have previously shown that HCV core protein promotes immortalization of primary human hepatocytes. To identify molecular changes involved in core protein-mediated immortalization, we have investigated differential gene expression by microarray analyses in primary human hepatocytes and HCV core gene introduced hepatocytes after senescence (early passage), immortalization (middle passage), and anchor-independent growth (late passage). Out of 33,000 human genes screened, 1918 transcripts were differentially expressed (&gt; 2-fold) in immortalized human hepatocytes (IHH) as compared to negative controls. Our analyses provided a molecular portrait of changes in gene expression associated with three distinct stages of hepatocytes after introduction of HCV core gene. Many of the overall changes were involved with important cellular pathways, including cell growth regulation, immune regulation, oxidative stress, and apoptosis. We focused on the Stat3 signaling pathway by further verifying selected pries at the protein level relevant to hepatocyte growth regulation. Our data suggested that the introduction of HCV core protein results in all increase in expression of IL-6, gp130, leptin receptor, and Stat3. Upregulation of these genes in turn may requlate c-myc and cyclin D1, downstream of the Stat3 signaling pathway. Identification of these modulated genes with potential roles may help in the selection of targets for therapies against HCV-mediated liver disease progression. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.virol.2006.02.023

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  • Hepatitis C virus core protein inhibits tumor necrosis factor alpha-mediated apoptosis by a protective effect involving cellular FLICE inhibitory protein 査読

    K Saito, K Meyer, R Warner, A Basu, RB Ray, R Ray

    JOURNAL OF VIROLOGY   80 ( 9 )   4372 - 4379   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    We have previously shown that hepatitis C virus (HCV) core protein modulates multiple cellular processes, including those that inhibit tumor necrosis factor alpha (TNF-alpha)-mediated apoptosis. In this study, we have investigated the signaling mechanism for inhibition of TNF-alpha-mediated apoptosis in human hepatoma (HepG2) cells expressing core protein alone or in context with other HCV proteins. Activation of caspase-3 and the cleavage of DNA repair enzyme poly (ADP-ribose) polymerase were inhibited upon TNF-alpha exposure in HCV core protein-expressing HepG2 cells. In vivo protein-protein interaction studies displayed an association between TNF receptor 1 (TNFR1) and TNFR1-associated death domain protein (TRADD), suggesting that the core protein does not perturb this interaction. A coimmunoprecipitation assay also suggested that HCV core protein does not interfere with the TRADD-Fas-associated death domain protein (FADD)-procaspase-8 interaction. Further studies indicated that HCV core protein expression inhibits caspase-8 activation by sustaining the expression of cellular FLICE (FADD-like interleukin-1 beta-converting enzyme)-like inhibitory protein (c-FLIP). Similar observations were also noted upon expression of core protein in context to other HCV proteins expressed from HCV full-length plasmid DNA or a replicon. A decrease in endogenous c-FLIP by specific small interfering RNA induced TNF-a-mediated apoptotic cell death and caspase-8 activation. Taken together, our results suggested that the TNF-alpha-induced apoptotic pathway is inhibited by a sustained c-FLIP expression associated with the expression of HCV core protein, which may play a role in HCV-mediated pathogenesis.

    DOI: 10.1128/JVI.80.9.4372-4379.2006

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  • Inhibition of hepatitis C virus core protein expression in immortalized human hepatocytes induces cytochrome c-independent increase in Apaf-1 and caspase-9 activation for cell death 査読

    K Meyer, A Basu, K Saito, RB Ray, R Ray

    VIROLOGY   336 ( 2 )   198 - 207   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Hepatitis C virus (HCV) core protein has multifunctional activities. We have previously reported that the core protein of HCV immortalizes primary human hepatocytes, which may relate to multistage hepatocarcinogenic events. These immortalized human hepatocytes (IHH) served as a model to study the mechanism of HCV core protein-mediated cell growth regulation. Inhibition of core protein expression in earlier stages after hepatocyte immortalization leads to the induction of apoptosis. Here, we have observed that introduction of antisense core (AS-Core) sequences for inhibition of core protein expression enhanced the expression of E2F1 and p53 levels in early passage IHH. Inhibition of core protein expression also altered the expression level of Bcl-2 family proteins, displaying an increase of the proapoptotic Bax and a decrease in the level of the anti-apoptotic Bcl-xL proteins. These alterations, however, did not result in the release of cytochrome c from the mitochondria. Apaf-1 is frequently deregulated under various pathologic conditions, and examination of AS-Core-expressing apoptotic cells indicated a significant increase in the level of Apaf-1, which coincided with caspase-9 activation. Knockdown of Apaf-l or the transcriptional regulatory proteins, E2F1 or p53, by small interfering RNA (siRNA) duplexes inhibited the activation of caspase-9 and enhanced cell viability in AS-Core-expressing cells. These findings may contribute to the understanding of the pathophysiology of HCV core protein-mediated hepatocyte growth regulation and disease progression. (c) 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.virol.2005.03.016

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  • Molecular visualization of immunoglobulin switch region RNA/DNA complex by atomic force microscope 査読

    R Mizuta, K Iwai, M Shigeno, M Mizuta, T Uemura, T Ushiki, D Kitamura

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 7 )   4431 - 4434   2003年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Immunoglobulin heavy-chain (IgH) class switch recombination (CSR) is initiated by DNA breakage in the switch (S) region featuring tandem repetitive nucleotide sequences. Various studies have demonstrated that S-region transcription and splicing proceed to genomic recombination and are indispensable for CSR in vivo, although the precise molecular mechanism is largely unknown. Here, we show the novel physical property of the in vitro transcribed S-region RNA by direct visualization using an atomic force microscope (AFM). The S-region sense RNA, but not the antisense RNA, forms a persistent hybrid with the template plasmid DNA and changes the plasmid conformation from supercoil to open circle in the presence of spermidine. In addition, the S-region transcripts generate globular forms and are assembled on the template DNA into a large aggregate that may stall replication and increase the recombinogenicity of the S-region DNA.

    DOI: 10.1074/jbc.M209262200

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  • The structure of human metaphase chromosomes: Its histological perspective and new horizons by atomic force microscopy 査読

    Tatsuo Ushiki, Osamu Hoshi, Kousuke Iwai, Eiji Kimura, Masatsugu Shigeno

    Archives of Histology and Cytology   65 ( 5 )   377 - 390   2002年12月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

    Studies on the structure of the human chromosome were reviewed from the histological perspective and discussed in connection with our recent findings obtained mainly by atomic force microscopy (AFM). In this paper, we introduce several hitherto known models of the high-order structure of the metaphase chromosome and discuss the actual structure of chromosomes in relation to such structures as spiral chromatids, chromosome bands, and chromosome scaffolds. In chromosomes treated with Ohnuki's hypotonic solution, the chromosome arms were elongated and showed a characteristic spiral pattern of chromatid fibers. On the other hand, alternating transverse ridges and grooves were clearly observed on the surface of chromosomes treated with 0.025% trypsin for G-banding, and these ridges and grooves corresponded to the dark and pale bands of G-banded chromosomes. Similar findings were also found in chromosomes treated with quinacrine mastards for Q-banding. Fibers bridging the gap between the sister chromatids were often observed in G/Q-banded chromosomes
    these fibers tended to be restricted within the G/Q-positive portions, suggesting the presence of chromatin fibers bridging these regions. Based on these findings in conjunction with previous studies, we outlined the highorder structure of the human chromosome. Recent advances in nanotechnology have provided new AFM techniques for the imaging and handling of materials at nano-scale resolution. Application of these techniques to chromosome research is expected to provide valuable information on the chromosome structure in relation to its function.

    DOI: 10.1679/aohc.65.377

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  • Human T-cell leukemia virus type 2 (HTLV-2) Tax protein transforms a rat fibroblast cell line but less efficiently than HTLV-1 Tax 査読

    K Endo, A Hirata, K Iwai, M Sakurai, M Fukushi, M Oie, M Higuchi, WW Hall, F Gejyo, M Fujii

    JOURNAL OF VIROLOGY   76 ( 6 )   2648 - 2653   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Human T-cell leukemia virus type I (HTLV-1) and HTLV-2 are retroviruses with similar biological properties. Whereas HTLV-1 is the causative agent of an aggressive T-cell leukemia, HTLV-2 has been associated with only a few cases of lymphoproliferative disorders. Taxi and Tax2 are the transcriptional activators of HTLV-1 and HTLV-2, respectively. Here we show that Tax2 transformed a Rat-1 fibroblast cell line to form colonies in soft agar, but the size and number of the colonies were lower than those of Taxi. Use of a chimeric Tax protein showed that the C-terminal amino acids 300 to 353 were responsible for the high transforming activity of Taxi. Activation of cellular genes by Taxi through transcription factor NF-kappaB is reportedly essential for the transformation of Rat-1 cells. Tax2 also activated the transcription through NF-kappaB in Rat-1 cells, and such activity was equivalent to that induced by Taxi. Thus, the high transforming activity of Taxi is mediated by mechanisms other than NF-kappaB activation. Our results showed that Tax2 has a lower transforming activity than Taxi and suggest that the high transforming activity of Taxi is involved in the leukemogenic property of HTLV-1.

    DOI: 10.1128/JVI.76.6.2648-2653.2002

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  • Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells 査読

    K Iwai, N Mori, M Oie, N Yamamoto, M Fujii

    VIROLOGY   279 ( 1 )   38 - 46   2001年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC  

    Human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of various family members of the transcription factor AP-I, such as c-Jun, JunD, c-Fos, and Fra-1, at the level of RNA expression in T cells. We examined the activity of Tax in transcription through AP-1-binding sites (AP-1 site) in T cells. Transient transfection studies showed that Tax activated the expression of a luciferase gene regulated by two copies of an AP-1 site in the human Jurkat T-cell line. Tax activates the expression of viral and cellular genes through two different enhancers: a cAMP-responsive (CRE)-like element and a KB element. Two Tax mutants differentially activated expression of these two elements. Tax703 preferentially activated the KB element but not the CRE-like one, whereas TaxM22 showed the reverse. In addition, Tax703 and Tax, but not TaxM22, converted cell growth of a mouse T-cell line from being interleukin (IL)-2-dependent to being Ii-a-independent. Unlike the wild-type Tax, Tax703 and TaxM22 only weakly activated the AP-1 site in the T-cell line. Thus, Tax seems to activate the AP-1 site via mechanisms distinct from those of KB Or CRE-like elements, and the activation of the AP-1 site is dispensable for IL-2-independent growth of CTLL-2. Electrophoretic mobility shift assays showed that Tax induced strong binding activity to an AP-1 site in CTLL-2, whereas Tax703 did not, indicating that the induction of binding activity to the AP-1 site is essential for the transcriptional activation by Tax. The binding complex induced by Tax in CTLL-2 contained JunD and Fra-2. Other AP-1 proteins were undetectable. Activation of transcription through the AP-1 site in Jurkat cells by JunD and/or Fra-2 was weak. c-Jun, JunB, and c-Fos activation was greater, although the level was still less than that with Tax. Thus, the induction of AP-1 mRNA by Tax may not be sufficient for a complete activation of AP-1 site by Tax. Our results suggest that Tax activates the transcription of cellular genes with AP-1 sites by inducing the DNA-binding activity of AP-1 proteins in T cells. a mechanism distinct from those of CRE-like and KB elements. (C) 2001 Academic Press.

    DOI: 10.1006/viro.2000.0669

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  • Interleukin-2-dependent but not independent T-cell lines infected with human T-cell leukemia virus type 1 selectively express CD45RO, a marker for persistent infection in vivo 査読

    H. Moro, K. Iwai, N. Mori, M. Watanabe, M. Fukushi, M. Oie, M. Arai, Y. Tanaka, T. Miyawaki, F. Gejyo, M. Arakawa, M. Fujii

    Virus Genes   23 ( 3 )   263 - 271   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia. HTLV-1 is exclusively detected in CD45RO+ T-cells in infected individuals, but CD45RO is weakly expressed in HTLV-1-transformed T-cell lines in vitro. The aim of this study was to investigate the role of CD45RO in the persistent HTLV-1 infection in vivo. Flow cytometry showed that only two out of eight interleukin(IL)-2-independent HTLV-1-transformed T-cell lines expressed CD45RO, whereas all five IL-2-dependent ones expressed CD45RO, and the level of expression was higher in IL-2-dependent than in IL-2-independent cells. The high CD45RO expression in IL-2-dependent cell lines was not due to IL-2, since IL-2 had little effect on the expression of CD45RO in T-cell lines. Using western blotting, we showed that IL-2-dependent HTLV-1-transformed T-cell lines expressed a lower level of expression of the viral transcriptional regulatory protein Tax than IL-2-independent ones, and that the level of expression correlated inversely with that of CD45RO. However, the expression of Tax in one HTLV-1-negative T-cell line little affected the expression of CD45RO, suggesting that Tax at least alone does not suppress the expression of CD45RO in HTLV-1-infected T-cell lines, and that other viral or cellular factor(s) are probably involved in such suppression. Our results suggest that CD45RO+ Tax-low IL-2-dependent T-cell lines in vitro correspond to the persistent HTLV-1-infected cells in vivo, and HTLV-1-infected cells in vivo are immortalized in IL-2-dependent manner.

    DOI: 10.1023/A:1012565105098

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  • Constitutive activation of transcription factor AP-1 in primary adult T-cell leukemia cells 査読

    Mori N, Fujii M, Iwai K, Ikeda S, Yamasaki Y, Hata T, Yamada Y, Tanaka Y, Tomonaga M, Yamamoto N

    BLOOD   95   3915 - 3921   2000年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Activation of oncogenic transcription factor AP-1 in T cells infected with human T cell leukemia virus type 1 査読

    MI Fujii, K Iwai, M Oie, M Fukushi, N Yamamoto, M Kannagi, N Mori

    AIDS RESEARCH AND HUMAN RETROVIRUSES   16 ( 16 )   1603 - 1606   2000年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT INC PUBL  

    Human T cell leukemia virus type 1 (HTLV-1) Tax protein transforms primary human T cells in vitro. We previously showed that Tax induces the expression of various family members of the transcription factor AP-1 such as c-Jun, JunD, c-Fos, and Fra-1 at the mRNA level in T cells. In this study, we have examined the ability of Tax to activate transcription through the AP-1-binding site (AP-1 site). A transient transfection study showed that Tax can activate transcription through the AP-1-binding site in a human T cell line, whereas any combination of AP-1 proteins did so much less than Tax, indicating that the activation of the AP-1 site by Tax may require a mechanism other than the induction of AP-1 mRNA. Fresh peripheral blood leukemia cells of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activity, whereas no normal individuals did. However, the NTLV-1 genes, including tax, are not significantly expressed in fresh leukemia cells from ATL patients. Our present results suggest that activation of AP-1 occurs through Tax-dependent and -independent mechanisms in HTLV-1-infected T cells, which may play some roles in dysregulated phenotypes of HTLV-1-infected cells.

    DOI: 10.1089/08892220050193029

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▶ 全件表示

書籍等出版物

  • 原理からよくわかるリアルタイムPCR完全実験ガイド

    齋藤孔良,鈴木康司,近藤大貴,日比野亮信,齋藤玲子( 範囲: Ⅳ章 遺伝子量解析 薬剤耐性インフルエンザウイルスを迅速に判定する)

    羊土社  2013年10月  ( ISBN:9784758101875

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    総ページ数:232, 6p   記述言語:日本語

    CiNii Books

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共同研究・競争的資金等の研究

  • 予防接種による認知症リスク減少のメカニズムを明らかにする高齢者コホート研究

    研究課題/領域番号:24K02854

    2024年4月 - 2029年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    齋藤 孔良

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    配分額:18460000円 ( 直接経費:14200000円 、 間接経費:4260000円 )

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  • 高齢者におけるワクチン忌避の要因を明らかにする研究

    研究課題/領域番号:21K10323

    2021年4月 - 2024年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    齋藤 孔良

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    ①研究代表者らは、ソーシャルキャピタル(社会的資本)が肺炎球菌予防接種を促す可能性を明らかにした研究成果を国際学術誌に発表した。65歳以上の高齢者に対するアンケート調査データを解析した結果、社会参加、社会的結束、互酬性の3つのソーシャルキャピタルがある高齢者は、それらのソーシャルキャピタルがない高齢者と比べて、肺炎球菌予防接種を受けている人がそれぞれ13%、5%、34%多いことを明らかにした。また、上記の3つのソーシャルキャピタルがなくても、社会参加の豊かな地域に住んでいる高齢者は、社会参加が標準的な地域に比べ肺炎球菌予防接種を受けている人が3%多いことを明らかにした(2021年5月18日、BMJ Open誌)。
    ②研究代表者らは、フレイル(老衰)高齢者では、フレイル無しの高齢者と比べて1.9倍肺炎にかかりやすく、また1.8倍肺炎が重症化しやすい(入院措置になりやすい)こと、また、フレイルの前段階にある高齢者でも、フレイル無しの高齢者と比べて1.3倍肺炎にかかりやすくなる可能性を明らかにした。また、研究代表者らは、口腔機能低下またはうつ状態に該当した高齢者は肺炎にかかりやすく、日常生活動作低下または閉じこもりに該当する高齢者では、肺炎で入院しやすくなる可能性を明らかにした(2021年4月12日、Scientific reports誌)。この研究成果は、フレイル高齢者において、予防接種により肺炎の発症および重症化を防ぐことが重要であることを裏付けた。

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  • 血液細胞特異的な新規RasGAPによるRasシグナルの制御機構

    2016年 - 2019年

    制度名:基盤研究(C)

    提供機関:新潟大学

    齋藤 孔良, 医歯学系

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • ストレス顆粒とオートファジーの蛋白分解クロストークの分子機構

    研究課題/領域番号:15H04704

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    藤井 雅寛, 小野寺 理, 小松 雅明, 高橋 雅彦, 蔭山 俊, 原 敏文, 樋口 雅也, 齋藤 孔良, 小山 哲秀, 葛城 美徳, 垣花 太一

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    配分額:16900000円 ( 直接経費:13000000円 、 間接経費:3900000円 )

    USP10はストレス顆粒の形成に重要な役割を果たす。全身性のUSP10欠損マウスを樹立した。USP10欠損マウスは汎血球減少症を発症した。USP10欠損マウスでは造血幹細胞のアポトーシスが昂進していた。SCF (stem cell factor)が造血幹細胞のアポトーシスを抑制するが、このSCFによる抑制は、USP10を欠損した造血幹細胞では著明に低下した。USP10の変異体は、脱ユビキチン化酵素活性がUSP10による造血幹細胞アポトーシスの抑制に関与することを示した。以上の結果は、USP10およびストレス顆粒が造血幹細胞の維持に関与することを示唆する。

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  • アジアを中心としたインフルエンザウイルスのグローバルな進化と薬剤耐性株の伝播追跡

    2013年 - 2016年

    制度名:基盤研究(B)

    提供機関:新潟大学

    齋藤 玲子, 医歯学系

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    資金種別:競争的資金

    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

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  • 特殊環状ペプチドによるインフルエンザウイルス増殖阻害効果における作用機序解明

    2011年

    制度名:若手研究(B)

    提供機関:(財)東京都医学総合研究所

    斎藤 孔良, 東京都医学総合研究所, 研究員

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    資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • ミャンマーの地理的特性に着目したインフルエンザ監視:多剤耐性と新型重症化

    研究課題/領域番号:22406013

    2010年 - 2012年

    制度名:基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:新潟大学

    齋藤 玲子, 医歯学系

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    資金種別:競争的資金

    配分額:18590000円 ( 直接経費:14300000円 、 間接経費:4290000円 )

    ミャンマーで2010-2012年度にヤンゴン市とネピドー市でインフルエンザの流行調査を行い、インフルエンザ株の特徴と薬剤耐性の解析を行った。3年間に643株のインフルエンザウイルスを分離し、A/H1N1pdm09 257株、A/H3N2 182株、B 204株が検出された。流行時期は5-11月の雨期であった。A/H3N2とB型は日本の冬の流行に半年先駆けて新しい遺伝子型の株がミャンマーで先行して流行した。薬剤耐性に関してはA/H1N1pdm09にオセルタミビル耐性株の出現は無かった。B型は2株がザナミビル、オセルタミビル、ラニナミビルに耐性を示し、NA遺伝子248位に変異(I248G)が認められた。

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  • HTLV-1感染によるNF-κB活性化におけるBcl-3の意義

    研究課題/領域番号:20790359

    2008年 - 2010年

    制度名:若手研究(B)

    研究種目:若手研究(B)

    提供機関:金沢医科大学

    斎藤 孔良, 医学部

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    資金種別:競争的資金

    配分額:2990000円 ( 直接経費:2300000円 、 間接経費:690000円 )

    Bcl-3のHTLV-1関連疾患への関与について明らかにすることを最終目標に、本年度は主にHTLV-1感染T細胞株を用いてT細胞の癌化及びT細胞機能異常におけるBd-3の関与を検討した。「研究計画1 : Bcl-3の恒常的NF-KB活性化への関与の有無の検討」に関しては、shRNAによるBcl-3発現挿制によってHTLV-1感染T細胞株の増殖が顕著に抑制されることを明らかにした。HTL-1感染T細胞の増殖にはNF-KB経路の活性化が重要であることがすでに報告されていることから、Bd-3の高発現が恒常的なNF-kB経路の活性化に関与する可能性がある。「研究計画2 : HTLV-1感染及びTax蛋白発現T細胞におけるBcl-3蛋白の発現調節のメカニズムの検討」に関しては、HTLV-1感染細胞内におけるBcl-3蛋白の高発現がBcl-3遺伝子のTaxによる転写活性化によってのみならず、PI3K-Akt経路の活性化によるBcl-3蛋白の分解抑制機構によっても維持されていること、Tax蛋白発現によりBcl-3蛋白の分解抑制が増強されることを明らかにした。「研究計画3 : Bcl-3蛋白発現レベルの変化とT細胞機能異常との関連の検討」に関しては、Bc1-3蛋白発現がHTLV-1感染T細胞株の異常増殖に関与することを明らかにした。今年度は以上3つの研究実施計画以外にも、HTLV-1感染T細胞内においてBcl-3がTaxと蛋白一蛋白間結合していること、さらには、Bc1-3蛋白のN, C末端領域のみからなる、すなわちAnkyrin repeatを欠く変異体がTax蛋白と効率良く結合してTaxによるHTLV-1LrRプロモーターやマトリックスメタロプロテアーゼ9プロモーターの活性化をintactなBc1-3と同等レベルで抑制するのに対して、Bd-3蛋白のN, C末端領域を欠く、すなわちAnkyrin repeat領域のみからなる変異体はTaxによるHTLV-1プロモーターの活性化をほとんど抑制しないことも明らかにした。

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担当経験のある授業科目

  • 保健医療福祉行政論

    2022年
    -
    現在
    機関名:新潟大学

  • 地域保健管理論

    2022年
    -
    現在
    機関名:新潟大学

  • 環日本海医療概論

    2014年
    機関名:新潟大学

 

メディア報道

  • 「フレイル」の高齢者 インフルエンザに1.36倍感染しやすく重症化も3.18倍 インターネットメディア

    テレ朝ニュース  テレビ朝日  2023年6月

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    執筆者:本人以外 

    高齢者のなかでも加齢によって心身が弱ったいわゆる「フレイル」の人は健康な人と比べて季節性インフルエンザにかかりやすく、重症化しやすいことが分かりました。

    新潟大学の齋藤孔良助教らの研究チームは、高齢者およそ7万7000人を対象にインフルエンザに感染したかどうかを調べました。

    その結果、心と身体が衰え、要介護状態の手前にある「フレイル」の高齢者は健康な人と比べて1.36倍インフルエンザにかかりやすいことが分かりました。

    また、感染した際に3.18倍、重症化しやすいことも明らかになったということです。

    これまで高齢者がインフルエンザに感染した場合、重症化しやすいことは明らかになっていましたが、「フレイル」との関係は分かっていませんでした。

    齋藤助教は「フレイル」の高齢者には「感染につながる行動はなるべく避け、ワクチンを接種してほしい」と呼び掛けています。

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  • フレイルのある高齢者はインフルエンザに1.4倍かかりやすい 重症化リスクも3.2倍 高齢男性でとくに深刻 インターネットメディア

    保健指導リソースガイド  2023年10月

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    フレイルのある高齢者では、健康な高齢者に比べ、インフルエンザに1.4倍かかりやすく、3.2倍重症化しやすいことが、日本の高齢者7.7万人を対象とした調査で明らかになった。

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  • 「フレイル」高齢者、インフル重症化リスク3・2倍…免疫弱い可能性(読者会員限定) インターネットメディア

    読売新聞オンライン  2023年8月

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  • 「フレイル」の高齢者 インフルエンザに1.36倍感染しやすく重症化も3.18倍 インターネットメディア

    メーテレ  2023年6月

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    執筆者:本人以外 

    高齢者のなかでも加齢によって心身が弱ったいわゆる「フレイル」の人は健康な人と比べて季節性インフルエンザにかかりやすく、重症化しやすいことが分かりました。 新潟大学の齋藤孔良助教らの研究チームは、高齢者およそ7万7000人を対象にインフルエンザに感染したかどうかを調べました。 その結果、心と身体が衰え、要介護状態の手前にある「フレイル」の高齢者は健康な人と比べて1.36倍インフルエンザにかかりやすいことが分かりました。 また、感染した際に3.18倍、重症化しやすいことも明らかになったということです。 これまで高齢者がインフルエンザに感染した場合、重症化しやすいことは明らかになっていましたが、「フレイル」との関係は分かっていませんでした。 齋藤助教は「フレイル」の高齢者には「感染につながる行動はなるべく避け、ワクチンを接種してほしい」と呼び掛けています。

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  • 堀ちゃんと学ぶフレイル予防 テレビ・ラジオ番組

    テレビ新潟  2022年2月

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  • フレイルがある高齢者は肺炎に1.9倍かかりやすく、1.8倍重症化しやすい 予備群でも肺炎リスクは1.3倍 インターネットメディア

    糖尿病リソースガイド  2021年8月

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    執筆者:本人以外 

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  • フレイルがある高齢者、肺炎に1.9倍かかりやすく、1.8倍重症化しやすい-新潟大 インターネットメディア

    QLifePro  医療NEWS  2021年7月

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    執筆者:本人以外 

    要介護認定を受けていない約18万人の高齢者データを解析
    新潟大学は7月26日、65歳以上の高齢者でフレイルがある場合、フレイルがない高齢者と比べて約1.9倍肺炎にかかりやすく、また、1.8倍肺炎が重症化しやすい(入院措置になりやすい)ことを明らかにしたと発表した。この研究は、同大大学院医歯学総合研究科国際保健学分野の齋藤孔良助教らの研究グループによるもの。研究成果は、「Scientific reports」に掲載されている。

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  • フレイル高齢者は1.9倍肺炎にかかりやすく、1.8倍重症化しやすい

    ティースデンタルオフィス  2021年7月

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    執筆者:本人以外 

    フレイルとは、加齢や病気による心身の衰えにより要介護になるリスクが高い状態をいいます。新潟大学大学院医歯学総合研究科国際保健学分野の齋藤孔良助教らの研究グループは、約18万人の65歳以上の高齢者における疫学調査を行いました。
    その結果、フレイルの65歳以上の高齢者では、フレイル無しの高齢者と比べて約1.9倍肺炎にかかりやすく、また、1.8倍肺炎が重症化しやすい(入院措置になりやすい)ことを明らかにしました。またフレイルの前段階にある高齢者でも、フレイル無しの高齢者と比べて1.3倍肺炎にかかりやすいことがわかりました。

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