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        Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with Rheumatoid Arthritis

        Akira Iwata,Kuniyoshi Abumi,Masahiko Takahata,Hideki Sudo,Katsuhisa Yamada,Tsutomu Endo,Norimasa Iwasaki 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.2

        Study Design: Retrospective case-control study, level 4. Purpose: To clarify the risk factors for late subaxial lesion after occipitocervical (O-C) reconstruction. We examined cases requiring fusion-segment-extended (FE) reconstruction in addition to/after O-C reconstruction. Overview of Literature: Patients with rheumatoid arthritis (RA) frequently require O-C reconstruction surgery for cranio-cervical lesions. Acceptable outcomes are achieved via indirect decompression using cervical pedicle screws and occipital plate–rod systems. However, late subaxial lesions may develop occasionally following O-C reconstruction. Methods: O-C reconstruction using cervical pedicle screws and occipital plate–rod systems was performed between 1994 and 2007 in 113 patients with RA. Occipito-atlanto-axial (O-C2) reconstruction was performed for 89 patients, and occipito-subaxial cervical (O-under C2) reconstruction was performed for 24 patients. We reviewed the cases of patients requiring FE reconstruction (fusion extended group, FEG) and 26 consecutive patients who did not require FE reconstruction after a follow-up of >5 years (non-fusion extended group, NEG) as controls. Results: FE reconstructions were performed for nine patients at an average of 45 months (range, 24–180 months) after O-C reconstruction. Of the 89 patients, three (3%) underwent FE reconstruction in cases of O-C2 reconstruction. Of the 24 patients, five (21%) underwent FE reconstruction in cases of O-under C2 reconstruction (p =0.003, Fisher exact test). Age, sex, RA type, and neurological impairment stage were not significantly different between FEG and NEG. O-under C2 reconstruction, larger correction angle (4° per number of unfixed segment), and O-C7 angle change after O-C reconstruction were the risk factors for late subaxial lesions on radiographic assessment. Conclusions: Overcorrection of angle at fusion segments requiring O-C7 angle change was a risk factor for late subaxial lesion in patients with RA with fragile bones and joints. Correction should be limited, considering the residual mobility of the cervical unfixed segments.

      • Enzymatic characterization of <i>in vitro</i>-expressed Baikal seal cytochrome P450 (CYP) 1A1, 1A2, and 1B1: Implication of low metabolic potential of CYP1A2 uniquely evolved in aquatic mammals

        Iwata, Hisato,Yamaguchi, Keisuke,Takeshita, Yoko,Kubota, Akira,Hirakawa, Shusaku,Isobe, Tomohiko,Hirano, Masashi,Kim, Eun-Young Elsevier 2015 Aquatic toxicology Vol.162 No.-

        <P><B>Abstract</B></P> <P>This study aimed to elucidate the catalytic function of cytochrome P450 (CYP) 1 enzymes in aquatic mammals. Alkoxyresorufin <I>O</I>-dealkylation (AROD) activities including methoxy- (MROD), ethoxy- (EROD), pentoxy- (PROD), and benzyloxyresorufin <I>O</I>-dealkylation (BROD), and 2- and 4-hydroxylation activities of 17β-estradiol (E<SUB>2</SUB>) were measured by using yeast-expressed Baikal seal (<I>Pusa sibirica</I>) CYP1A1, 1A2, and 1B1 proteins. Heterologous protein expression of the Baikal seal CYP1s (bsCYP1s) in yeast microsomes was confirmed by reduced CO-difference spectra and immunoblotting. Heterologously expressed human CYP1 enzyme (hCYP1) activities were simultaneously measured and compared with those of bsCYP1 isozymes. Recombinant bsCYP1A1 protein showed the highest <I>V</I> <SUB>max</SUB> of EROD, followed by MROD, PROD, and BROD, similar to that of hCYP1A1. <I>V</I> <SUB>max</SUB>/<I>K</I> <SUB>m</SUB> ratios of all AROD activities catalyzed by bsCYP1A1 were lower than those catalyzed by hCYP1A1, suggesting less potential for AROD by bsCYP1A1. Enzymatic assays for bsCYP1A2 showed no or minimal AROD activities, while hCYP1A2 displayed MROD and EROD activities. bsCYP1B1 showed an AROD profile (EROD>BROD>MROD>>PROD) similar to that of hCYP1B1; however, <I>V</I> <SUB>max</SUB>/<I>K</I> <SUB>m</SUB> ratios of all AROD activities by bsCYP1B1 were higher. Yeast microsomes containing bsCYP1A1 and 1B1 and hCYP1A1, 1A2, and 1B1 metabolized E<SUB>2</SUB> to 2-OHE<SUB>2</SUB> and 4-OHE<SUB>2</SUB>, whereas bsCYP1A2 showed no such activity. Comparison of 4- and 2-hydroxylations of E<SUB>2</SUB> by CYP1As suggests that bsCYP1A1, hCYP1A1, and 1A2 preferentially catalyze 2- rather than 4-hydroxylation. As for CYP1B1, the <I>V</I> <SUB>max</SUB>/<I>K</I> <SUB>m</SUB> ratios suggest that both Baikal seal and human CYPs catalyze 4- rather than 2-hydroxylation. Interspecies comparison showed that bsCYP1B1 has higher metabolic potencies for both E<SUB>2</SUB> hydroxylations than does hCYP1B1, whereas the activity of bsCYP1A1 was lower than that of hCYP1A1. Messenger RNA expression levels of bsCYP1s in the liver of Baikal seals indicated that bsCYP1A1 and 1A2 enzymes contributed to 16.2% and 83.7% of total CYP1s, respectively; bsCYP1B1 accounted for only 0.06%. Addition of anti-human CYP1A1 antibody in seal liver microsomes suppressed EROD activity more than did anti-human CYP1A2 antibody. Therefore, EROD may be catalyzed by hepatic bsCYP1A1 but not bsCYP1A2, consistent with the results of yeast-expressed bsCYP1A1 and 1A2. <I>In silico</I> substrate-docking models of bsCYP1s suggested that the defect in bsCYP1A2 enzymatic activities may be accounted for by the Pro substitution of highly conserved Thr in the I-helix, which is involved in formation of a hydrogen bond with the hydroperoxy intermediate on the heme. This Thr-Pro substitution is evolutionarily conserved across aquatic mammals and could explain their lower metabolic potential for persistent organic pollutants.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Catalytic activities of Baikal seal CYP1A1 were lower than those of human CYP1A1. </LI> <LI> Baikal seal CYP1B1 showed higher catalytic activities than human CYP1B1. </LI> <LI> Catalytic activities by Baikal seal CYP1A2 showed no or a minimal detectable value. </LI> <LI> Pro317 substitution appears to render seal CYP1A2 incapable of its catalytic function. </LI> <LI> This substitution is evolutionarily conserved in aquatic mammals. </LI> </UL> </P>

      • A Novel Low-Voltage CMOS Voltage Reference Circuit Insensitive to VDD and Temperature Variations

        Akira Nakajima,Takahiro Inoue,Akio Tsuneda,Kazuki Iwata 대한전자공학회 2007 ITC-CSCC :International Technical Conference on Ci Vol.2007 No.7

        A novel low-voltage CMOS voltage reference circuit insensitive to VDD and temperature variations is proposed in this paper. A reference voltage with low temperature dependency is achieved by canceling the negative temperature dependency of MOSFET’s threshold voltage by the PTAT voltage. The output reference voltage of 510㎷ is realized and its temperature dependency is 39ppm/℃ in the temperature range from -20℃ to 80℃. The proposed circuit can work at the voltage supply of 0.9V.

      • Alternative In Vitro Approach for Assessing AHR-Mediated CYP1A Induction by Dioxins in Wild Cormorant (<i>Phalacrocorax carbo</i>) Population

        Thuruthippallil, Leena Mol,Kubota, Akira,Kim, Eun-Young,Iwata, Hisato American Chemical Society 2013 Environmental science & technology Vol.47 No.12

        <P>Our line of papers revealed that the common (great) cormorant (<I>Phalacrocorax carbo</I>) possesses two isoforms of the aryl hydrocarbon receptor (<I>cc</I>AHR1 and <I>cc</I>AHR2). This paper addresses in vitro tests of the <I>cc</I>AHR signaling pathways to solve two questions: (1) whether there are functional differences in the two <I>cc</I>AHR isoforms, and (2) whether a molecular perturbation, cytochrome P450 1A (<I>cc</I>CYP1A) induction, in the population-level can be predicted from the in vitro tests. The transactivation potencies mediated by <I>cc</I>AHR1 and <I>cc</I>AHR2 were measured in COS-7 cells treated with 15 selected dioxins and related compounds (DRCs), where <I>cc</I>AHR1 or <I>cc</I>AHR2 expression plasmid and <I>cc</I>CYP1A5 promoter/enhancer-linked luciferase reporter plasmid were transfected. For congeners that exhibited dose-dependent luciferase activities, 2,3,7,8-tetrachlorodibenzo-<I>p</I>-dioxin (TCDD) relative potencies (REPs) and induction equivalency factors (IEFs) were estimated. <I>cc</I>AHR1-IEF profile was similar to WHO avian TCDD toxic equivalency factor (TEF) profile except for dioxin-like polychlorinated biphenyls that showed lower IEFs in <I>cc</I>AHR1-driven reporter assay. <I>cc</I>AHR2-IEF profile was different from WHO TEFs and <I>cc</I>AHR1-IEFs. Notably, 2,3,4,7,8-PeCDF was more potent than TCDD for <I>cc</I>AHR2-mediated response. Using <I>cc</I>AHR1- and <I>cc</I>AHR2-IEFs and hepatic DRC concentrations in the Lake Biwa cormorant population, total TCDD induction equivalents (IEQs) were calculated for each <I>cc</I>AHR-mediated response. Nonlinear regression analyses provided significant sigmoidal relationships of <I>cc</I>AHR1- and <I>cc</I>AHR2-derived IEQs with hepatic <I>cc</I>CYP1A5 mRNA levels, supporting the results of in vitro <I>cc</I>AHR-mediated TCDD dose–response curves. Collectively, our in vitro AHR reporter assay potentially could be an alternative to molecular epidemiology of the species of concern regarding CYP1A induction by AHR ligands.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/esthag/2013/esthag.2013.47.issue-12/es401155g/production/images/medium/es-2013-01155g_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/es401155g'>ACS Electronic Supporting Info</A></P>

      • Watermarking Method Resistant to Geometrical Slight Distortion Using Variance of Color Difference and Wavelet Transform

        Kei Sakiyama,Motoi Iwata,Akio Ogihara,Akira Shiozaki 대한전자공학회 2008 ITC-CSCC :International Technical Conference on Ci Vol.2008 No.7

        In this paper, we propose a watermarking method that has robustness against geometrical slight distortions. The method is based on the variances of two color ceomponents of an image. We use YCbCr components. When an image is geometrically distorted, Cb and Cr components on the same position cause the same distortion, and the relation of variances of Cb and Cr components in a local domain does not change easily. So we embed a watermark by changing the variances of Cb and Cr components so that the watermark may be robust against geometrical distortions. Moreover we use discrete wavelet transform so as to be robust against JPEG compression.

      • Digital Watermarking Method Using Variance of Chrominance in the Pairs of Adjoining Blocks

        Kei Sakiyama,Motoi Iwata,Akio Ogihara,Akira Shiozaki 대한전자공학회 2009 ITC-CSCC :International Technical Conference on Ci Vol.2009 No.7

        We propose a watermarking method that has robustness against geometrical slight distortions. The method is based on the variances of Cb and Cr components of an image. When a color image is geometrically distorted, Cb and Cr components on the same position cause the same distortion, and so the relation of variances of Cb and Cr components in a local region does not change easily. We embed each bit of a watermark into some adjacent local regions by changing the variances of Cb and Cr components so that the watermark may be robust to geometrical distortions.

      • An Action-Selection Strategy Insensitive to Parameter-Settings in Reinforcement Learning

        Kenji Ono,Kazunori Iwata,Akira Hayashi 제어로봇시스템학회 2009 제어로봇시스템학회 국제학술대회 논문집 Vol.2009 No.8

        Markov decision processes are one of the most popular frameworks for reinforcement learning. The entropy of probability density functions of Markv decision processes is referred to as the stochastic complexity. The stochastic complexity is helpful for tuning the parameters of an action-selection strategy to alleviate the exploration-exploitation dilemma. In this paper, we improve an action-selection strategy to make it insensitive to parameter-settings by using the stochastic complexity. This gives better policies for alleviating the above dilemma in most parameter-settings.

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