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      • Trade-off between Processivity and Hydrolytic Velocity of Cellobiohydrolases at the Surface of Crystalline Cellulose

        Nakamura, Akihiko,Watanabe, Hiroki,Ishida, Takuya,Uchihashi, Takayuki,Wada, Masahisa,Ando, Toshio,Igarashi, Kiyohiko,Samejima, Masahiro American Chemical Society 2014 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.136 No.12

        <P>Analysis of heterogeneous catalysis at an interface is difficult because of the variety of reaction sites and the difficulty of observing the reaction. Enzymatic hydrolysis of cellulose by cellulases is a typical heterogeneous reaction at a solid/liquid interface, and a key parameter of such reactions on polymeric substrates is the processivity, i.e., the number of catalytic cycles that can occur without detachment of the enzyme from the substrate. In this study, we evaluated the reactions of three closely related glycoside hydrolase family 7 cellobiohydrolases from filamentous fungi at the molecular level by means of high-speed atomic force microscopy to investigate the structure–function relationship of the cellobiohydrolases on crystalline cellulose. We found that high moving velocity of enzyme molecules on the surface is associated with a high dissociation rate constant from the substrate, which means weak interaction between enzyme and substrate. Moreover, higher values of processivity were associated with more loop regions covering the subsite cleft, which may imply higher binding affinity. Loop regions covering the subsites result in stronger interaction, which decreases the velocity but increases the processivity. These results indicate that there is a trade-off between processivity and hydrolytic velocity among processive cellulases.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-12/ja4119994/production/images/medium/ja-2013-119994_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja4119994'>ACS Electronic Supporting Info</A></P>

      • SCISCIESCOPUS

        Two-Dimensionally Extended Porphyrin Tapes: Synthesis and Shape-Dependent Two-Photon Absorption Properties

        Nakamura, Yasuyuki,Jang, So Young,Tanaka, Takayuki,Aratani, Naoki,Lim, Jong Min,Kim, Kil Suk,Kim, Dongho,Osuka, Atsuhiro WILEY-VCH Verlag 2008 Chemistry Vol.14 No.27

        <P>We report the synthesis and characterization of L- and T-shaped porphyrin tapes as extensible structural motifs of two-dimensionally extended porphyrin tapes. The two-photon absorption (TPA) cross-section values (σ<SUP>(2)</SUP>) for L- and T-shaped porphyrin tapes as well as those for linear trimeric and tetrameric porphyrin tapes were measured by an open-aperture Z-scan method at 2300 nm, a wavelength at which the one-photon absorption contribution is either zero or almost negligible. Under these conditions, the σ<SUP>(2)</SUP> values for the linear porphyrin tape trimer and tetramer were determined to be 18 500 and 41 200 GM, respectively. The σ<SUP>(2)</SUP> value for the L-shaped trimer was determined to be 8700 GM, which is only half that of the linear trimer, whereas the σ<SUP>(2)</SUP> value for the T-shaped tetramer was measured to be 35 700 GM. These results clearly indicate the dependence of the TPA cross-section on the molecular shape, which underscores the importance of directionality in the π-conjugation pathway for the enhancement of TPA cross- section.</P> <B>Graphic Abstract</B> <P>Fused porphyrins: L- and T-shaped porphyrin tapes have been synthesized as extensible structural motifs of 2D extended-porphyrin tapes (see figure). Systematic measurement of the two-photon adsorption (TPA) properties of linear, L-, and T-shaped porphyrin tapes clearly indicate the importance of directionality in the π-conjugation pathway for the enhancement of the TPA properties. <img src='wiley_img/09476539-2008-14-27-CHEM200800776-content.gif' alt='wiley_img/09476539-2008-14-27-CHEM200800776-content'> </P>

      • KCI등재

        Development of a prognostic prediction support system for cervical intraepithelial neoplasia using artificial intelligence-based diagnosis

        Takayuki Takahashi,Hikaru Matsuoka,Rieko Sakurai,Jun Akatsuka,Yusuke Kobayashi,Masaru Nakamura,Takashi Iwata,Kouji Banno,Motomichi Matsuzaki,Jun Takayama,Daisuke Aoki,Yoichiro Yamamoto,Gen Tamiya 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5

        Objective: Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. Methods: We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. Results: High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). Conclusion: Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2.

      • KCI등재

        Angiopoietin-Like Protein 2 Induces Synovial Inflammation in the Facet Joint Leading to Degenerative Changes via Interleukin-6 Secretion

        Kazuki Sugimoto,Takayuki Nakamura,Takuya Tokunaga,Yusuke Uehara,Tatsuya Okada,Takuya Taniwaki,Toru Fujimoto,Yuichi Oike,Eiichi Nakamura 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.3

        Study Design: Experimental human study. Purpose: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. Overview of Literature: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is highly expressed in degenerative FJ synovial tissue and is responsible for local chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, promotes the expression of IL-6 in many cells. Methods: FJ tissues were harvested from five patients who had undergone lumbar surgery. Immunohistochemistry for ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After cultured synoviocytes from the FJ tissues were subjected to mechanical stress, ANGPTL2 expression and secretion were measured quantitatively using real-time quantitative reverse-transcription–polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in the FJ synoviocytes, anti-nuclear factor-κB (NF-κB) activation was investigated using immunocytochemistry, and IL-6 expression and secretion were assayed quantitatively with or without NF-κB inhibitor. Moreover, we assessed whether ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. Results: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ synoviocytes increased in response to stimulation by mechanical stretching. ANGPTL2 protein promoted the nuclear translocation of NF-κB and induced IL-6 expression and secretion in the FJ synoviocytes. This effect was reversed following treatment with NF-κB inhibitor. Furthermore, ANGPTL2-induced IL-6 upregulated the MCP-1 expression in the FJ synoviocytes. Conclusions: Mechanical stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.

      • KCI등재

        Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy

        Masayuki Sekine,Takayuki Enomoto,Masami Arai,Hiroki Den,Hiroyuki Nomura,Takeshi Ikeuchi,Seigo Nakamura 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.4

        Objective: and mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers. Methods: We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received genetic testing. Among them, germline mutation (g m), germline mutation (g m) and germline wild-type (g wt) were found in 185, 42 and 241 OC patients, respectively. Results: The average age at diagnosis of OC in g m and g m was 51.3 and 58.3 years, respectively, and the difference from g wt (53.8 years) was significant. Theg m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in , and 55.1 years for R2318X and 61.1 years for STOP1861 in . The age at diagnosis in L63X or R2318X carriers was relatively younger than other or carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40. Conclusion: There appears to be no difference in the age at diagnosis of OC depending on the type of common mutation. Further analysis would be needed.

      • KCI등재

        Development of New Organ Preservation Solutions in Kyoto University

        Fengshi Chen,Takayuki Nakamura,Hiromi Wada 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.6

        Although lung transplantation (LTx) has been established as a therapeutic approach for end-stage respiratory failure, several problems remain to be solved. In addition to the serious problem of donor shortage, primary graft failure, which is mostly caused by ischemia-reperfusion injury, a serious problem, and represents one of the most frequent causes of early mortality. The development of a highly reliable organ preservation solution that reduces ischemia-reperfusion injury will improve the functioning of transplanted organs and alleviate the donor shortage. We first evaluated the importance of saccharides and electrolytes in the lung preservation solution. We proved the superiority of trehalose, a non-reducing disaccharide, and the efficiency of the extracellular-type (low potassium) ion composition, and we also developed an extracellular-type trehalose containing Kyoto (ET-Kyoto) solution. Furthermore, several agents for vascular endothelial protection were evaluated, and finally, a more effective solution named “new ET-Kyoto solution” was developed, by adding N-acetylcysteine, dibutyryl adenosine 3', 5'-cyclic monophosphate, and nitroglycerin to the “conventional” ET-Kyoto solution. The new ET-Kyoto solution enabled canine LTx to last up to 30 hours. ET-Kyoto solution has so far been used and produced good results in five clinical LTx throughout Japan and South Korea. Although it was initially developed for lung preservation, its effectiveness in the preservation of various organs/ tissues, such as the trachea, kidney, skin/muscle flap, amputated digits, liver, and pancreas, has also been experimentally and clinically shown. In this paper, clinical and experimental findings with ET-Kyoto solution have been accumulated to further analyze its effect, safety, and chemical stability. We hope to provide ET-Kyoto solution as the standard organ/tissue preserving solution throughout the world.

      • KCI등재

        Characteristics of Primary and Metachronous Gastric Cancers Discovered after Helicobacter pylori Eradication: A Multicenter Propensity Score- Matched Study

        ( Yuji Maehata ),( Shotaro Nakamura ),( Motohiro Esaki ),( Fumie Ikeda ),( Tomohiko Moriyama ),( Risa Hida ),( Ema Washio ),( Junji Umeno ),( Minako Hirahashi ),( Takanari Kitazono ),( Takayuki Matsum 대한간학회 2017 Gut and Liver Vol.11 No.5

        Background/Aims: Gastric cancers develop even after suc-cessful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication. Methods: A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dis-section were included. After matching the propensity score, we retrospectively investigated the clinicopathological fea-tures of 192 patients, including 96 patients who had under-gone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group). Results: In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive pa-tients, Hp-eradicated patients showed a more frequently de-pressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp-eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers. Conclu-sions: Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow- up endoscopies are necessary after H. pylori eradication. (Gut Liver 2017;11:628-634)

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