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( Ken Fukunaga ),( Yoko Yokoyama ),( Koji Kamokozuru ),( Kazuko Nagase ),( Shiro Nakamura ),( Hiroto Miwa ),( Takayuki Matsumoto ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.4
Background/Aims: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. Methods: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. Results: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid- free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. Conclusions: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy. (Gut Liver 2012;6:427-433)
( Ken Fukunaga ),( Kazuko Nagase ),( Takeshi Kusaka ),( Nobuyuki Hida ),( Yoshio Ohda ),( Koji Yoshida ),( Katsuyuki Tozawa ),( Koji Kamikozuru ),( M Iimuro ),( Shiro Nakamura ),( Hiroto Miwa ),( Taka 대한소화기기능성질환·운동학회 2009 Gut and Liver Vol.3 No.1
Background/Aims: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. Methods: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of ≥7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. Results: CAP induced clinical remission (CAI≤4) in 70.2% patients (33/47). The number of submissions for colectomy was higher for severe UC at entry (CAI≥12, n=25) than for moderately severe UC at entry (7≤CAI<12, p=15; p<0.02). The cumulative rates of avoiding surgery and relapse were 54.5% and 24.2%, respectively, at 36 months in patients who responded to CAP therapy. This was similar to that of iv cyclosporine reported recently. Conclusions: This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC. (Gut and Liver 2009;3:41-47)
Ken Yoshida,Hideya Yamazaki,Satoaki Nakamura,Koji Masui,Tadayuki Kotsuma,Hironori Akiyama,Eiichi Tanaka,Nobuhiko Yoshikawa,Yasuo Uesugi,Taiju Shimbo,Yoshifumi Narumi,Yasuo Yoshioka 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.3
Objective: To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. Methods: We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). Results: More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2–3 at 6 months was only a statistically significant predisposing factor for grade 2–3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0–1 pallor reaction at 6 months showed a grade ≥2 vaginal stenosis rate of 53%, whereas the grade 2–3 pallor reaction group achieved a grade ≥2 vaginal stenosis rate at 3 years at 100% (p=0.001). Conclusion: High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2–3 at 6 months was predictive of late grade 2–3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.
Ken Hoshikawa,Ikuo Nakamura,Satoshi Endo,Shingo Mizuniwa,So Makabe,Hiroko Takahashi 한국식물생명공학회 2012 Plant biotechnology reports Vol.6 No.3
Genes encoding pathogenesis-related proteins,such as degrading enzymes of fungal cell wall polysaccharides,have been used to confer enhanced resistance to fungal pathogens of various plants. A new type of endo-bmannanase gene, amn5A, was isolated from alkaliphilic Bacillus strain (JAMB-602) found in deep-sea sediment. The AMN5A mannanase is active over a wide pH range (pH 7–10) and stable at high temperature. In this study,transgenic tobacco plants expressing the amn5A gene were generated using Agrobacterium-mediated transformation. Polymerase chain reaction (PCR) analysis revealed that the amn5A gene was integrated into the genome of transgenic tobacco plants. Southern blot analysis showed that transgenic plants contained 1–6 copies of amn5A transgenes in their genome. Expression of the amn5A transgene was confirmed by reverse transcription-PCR analysis. Leaf extracts from the transgenic plants showed degradation activity of Konjak mannan. Antifungal assay of detached leaves and in vitro whole plantlets indicated that transgenic plants expressing amn5A gene acquired enhanced resistance to the soil-borne pathogenic fungus, Fusarium oxysporum,compared to untransformed control plants.
Interleukin-34 cancels anti-tumor immunity by PARP inhibitor
Takayoshi Nakamura,Nabeel Kajihara,Naoki Hama,Takuto Kobayashi,Ryo Otsuka,Nanumi Han,Haruka Wada,Yoshinori Hasegawa,Nao Suzuki,Ken-ichiro Seino 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3
Objective: Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). Methods: In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. Results: We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. Conclusion: These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.
Deriving Safety Properties for Home Network System Based on Goal-Oriented Hazard Analysis Model
Ben Yan,Ken-ichi Matsumoto,Masahide Nakamura 보안공학연구지원센터 2009 International Journal of Smart Home Vol.3 No.1
The home network system (HNS, for short) is comprised of networked home appliances, which achieves various value-added services for home users. Assuring safety of the HNS and the services is a crucial issue. However, safety properties to be verified against the HNS have been given in an ad-hoc manner. This paper presents a systematic method that can derive the verifiable safety properties from a given HNS model and hazard contexts. Specifically, we first define a hazard analysis model for the HNS consisting of four levels of abstractions. We then conduct a goal-oriented analysis to specify logical relations between the adjacent abstraction levels. The analysis yields cause-and-effect chains from the abstract hazard contexts to the concrete attributes and operations of HNS objects (appliances, services, environment). Finally, the safety properties and their responsible operations are derived from the complete model, which give the strong rationale of the safety of the HNS.
Ben Yan,Ken-ichi Matsumoto,Masahide Nakamura,Lydie du Bousquet 보안공학연구지원센터 2009 International Journal of Smart Home Vol.3 No.2
The recent ubiquitous/pervasive technologies allow general household appliances to be connected within the network at home. The home network system (HNS, for short) is comprised of such networked appliances to provide various services and applications for home users. The great advantage of HNS lies in integrating (or orchestrating) features of multiple appliances, which yields more value-added and powerful services. We call such services HNS integrated services. In developing and providing a HNS integrated service, the service provider must guarantee that the service is safe for inhabitants, house properties and their surrounding environment. As for the HNS integrated services, however, we have to consider the safety much more carefully. This paper presents a systematic method that can derive the verifiable safety properties from a given HNS model and hazard contexts. Specifically, we propose the HNS Hazard Analysis Model (HNS-HAM) for deriving safety properties with conducting a goal-oriented analysis. The analysis yields cause-and-effect chains from the abstract hazard contexts to the concrete attributes and operations of HNS objects (appliances, services, and environment). Then the safety properties and their responsible operations are derived from the complete model, which give the strong rationale of the safety of the HNS. On the other hand, to make the proposed method more practical, it is necessary to save the analysis cost while appliances and services in the HNS are added or changed. For this, we have also proposed the notion of the hazard template, which characterizes the generic portion of the HNS-HAM. For every hazard context, the hazard template is supposed to be constructed once by the safety experts. The template can be reused for various kinds of the HNS objects for the common hazard context. The reusable templates make it possible to save the analysis cost and improve the quality of the HNS-HAM.