79 results on '"Koike, M."'
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2. FLEXIBLE PROCESS PLANNING SYSTEM CONSIDERING DESIGN INTENTIONS AND DISTURBANCE IN PRODUCTION PROCESS
- Author
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Han, G, primary, Koike, M., additional, Wakamatsu, H., additional, Tsumaya, A., additional, Arai, E, additional, and Shirase, K., additional
- Published
- 2007
- Full Text
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3. Ultrasonic nondestructive testing method for heavy plate butt welds using low frequency broadband angle probe and synthetic aperture focusing technique
- Author
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Wadaka, S., primary, Koike, M., additional, Kimura, T., additional, Kameyama, S., additional, and Manome, Y., additional
- Published
- 2000
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4. List of participants
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Abe, M., primary, Abo, M., additional, Abukawa, T., additional, Adachi, J., additional, Agui, A., additional, Aita, O., additional, Aiura, Y., additional, Ajello, J., additional, Akaki, O., additional, Akazawa, H., additional, Aksela, H., additional, Aksela, S., additional, Allen, J., additional, Altun, Z., additional, Amemiya, K., additional, Amusia, M., additional, An, K., additional, Andersen, J., additional, Aoki, S., additional, Arakawa, I., additional, Araki, T., additional, Arp, U., additional, Asensio, M., additional, Awaya, Y., additional, Awazu, K., additional, Azuma, H., additional, Azuma, Y., additional, Baba, Y., additional, Bando, H., additional, Bao, Z., additional, Becker, U., additional, Bengtsson, P., additional, Bobashev, S., additional, Bocquet, A., additional, Breton, J., additional, Cai, Y., additional, Caldwell, C., additional, Cauletti, C., additional, Chainani, A., additional, Che, J., additional, Chen, C., additional, Chen, L., additional, Chen, X., additional, Cherepkov, N., additional, Cho, T., additional, Christou, C., additional, Chung, J., additional, Couprie, M., additional, Cramer, S., additional, Da Silva, L., additional, Daimon, H., additional, Deguchi, K., additional, Dessau, D., additional, Dhanak, V., additional, Dolmatov, V., additional, Drube, W., additional, Echigo, S., additional, Ehresmann, A., additional, Eisebitt, S., additional, Ejima, T., additional, Ejiri, A., additional, Endo, O., additional, England, J., additional, Enta, Y., additional, Fadley, C., additional, Feldhaus, J., additional, Filatova, E., additional, Finazzi, M., additional, Finkenthal, M., additional, Fischer, D., additional, Flechsig, U., additional, Franzén, K., additional, Frasinski, L., additional, Fujikawa, T., additional, Fujimori, A., additional, Fujimori, S., additional, Fujisawa, M., additional, Fujita, K., additional, Fujita, M., additional, Fukui, K., additional, Fukutani, H., additional, Ghijsen, J., additional, Gluskin, E., additional, Guo, Q., additional, Guyon, P., additional, Hague, C., additional, Hall, R., additional, Hamamatsu, H., additional, Han, Z., additional, Hansen, J., additional, Hanyu, T., additional, Happo, N., additional, Hara, T., additional, Harada, I., additional, Harada, Y., additional, Hasegawa, M., additional, Hasegawa, S., additional, Hatano, T., additional, Hatherly, P., additional, Hattori, T., additional, Hayaishi, T., additional, Hayasi, T., additional, Heck, C., additional, Heinzmann, U., additional, Hieda, K., additional, Higashiyama, K., additional, Hirai, Y., additional, Hiraya, A., additional, Hirayama, T., additional, Hirose, S., additional, Hishikawa, A., additional, Hopkirk, A., additional, Horikawa, Y., additional, Hosaka, N., additional, Huber, K., additional, Huff, W., additional, Hussain, Z., additional, Hwang, C., additional, Ibrahim, K., additional, Ibuki, T., additional, Ichikawa, K., additional, Ichikawa, M., additional, Igarashi, J., additional, Iguchi, Y., additional, Iimura, K., additional, Iinuma, D., additional, Iketaki, Y., additional, Ikeura, H., additional, Imada, S., additional, Imaizumi, Y., additional, Imanishi, A., additional, Inokuchi, H., additional, Inoue, I., additional, Ishigame, M., additional, Ishiguro, E., additional, Ishii, H., additional, Ishii, T., additional, Ishijima, H., additional, Ishizue, I., additional, Isoyama, G., additional, Ito, K., additional, Itoh, M., additional, Itoh, Y., additional, Iwami, M., additional, Iwano, K., additional, Iwasaki, K., additional, Iwata, S., additional, Jacobsen, C., additional, Jikimoto, T., additional, Jo, T., additional, Johansson, L., additional, Johansson, U., additional, Jouda, K., additional, Jung, C., additional, Kabachnik, N., additional, Kaindl, G., additional, Kakizaki, A., additional, Kamada, M., additional, Kamata, A., additional, Kamenskikh, I., additional, Kameta, K., additional, Kamiya, K., additional, Kamiya, Y., additional, Kan'no, K., additional, Kanomata, T., additional, Kasaya, M., additional, Kashiwakura, T., additional, Kato, R., additional, Kato, Y., additional, Katoh, R., additional, Kaurila, T., additional, Kawai, J., additional, Kawamura, T., additional, Kayanuma, Y., additional, Kaznacheyev, K., additional, Kennedy, E., additional, Kiguchi, M., additional, Kihara, H., additional, Kimpara, Y., additional, Kimura, A., additional, Kimura, H., additional, Kimura, K., additional, Kimura, S., additional, Kinoshita, T., additional, Kirm, M., additional, Kisker, E., additional, Kitade, T., additional, Kitajima, M., additional, Kitajima, Y., additional, Kitamura, H., additional, Kitaura, M., additional, Kobayashi, K., additional, Kobayashi, M., additional, Koda, T., additional, Kohagura, J., additional, Koide, T., additional, Koike, F., additional, Koike, M., additional, Koike, T., additional, Koizumi, T., additional, Kojima, T., additional, Kondo, K., additional, Kondo, Y., additional, Kono, M., additional, Kono, S., additional, Korde, R., additional, Koseki, T., additional, Kosugi, N., additional, Kotani, A., additional, Kotani, M., additional, Kouchi, N., additional, Kowalski, M., additional, Koyama, M., additional, Koyano, I., additional, Krause, M., additional, Krupa, J., additional, Kumigashira, H., additional, Kuninobu, T., additional, Kurita, S., additional, Kusaka, M., additional, Kutluk, G., additional, Lablanquie, P., additional, Lama, F., additional, Larkins, F., additional, Latimer, C., additional, Lebrun, T., additional, Lee, D., additional, Lee, K., additional, Lee, T., additional, Legrand, F., additional, Lewis, B., additional, Li, D., additional, Lindau, I., additional, Liu, F., additional, Lodha, G., additional, Lu, E., additional, Lushchik, A., additional, Lyakhovskaya, I., additional, Mårtensson, N., additional, Ma, Y., additional, Machida, S., additional, Maeda, F., additional, Maeyama, S., additional, Maezawa, H., additional, Manakov, N., additional, Margaritondo, G., additional, Masui, S., additional, Masuoka, T., additional, Matsui, F., additional, Matsukawa, T., additional, Matsumoto, M., additional, Matsumoto, S., additional, Matsushita, T., additional, Matsuzawa, M., additional, Mattogno, G., additional, Messina, A., additional, Mikhailin, V., additional, Mimura, K., additional, Minami, T., additional, Misu, A., additional, Mitsuishi, T., additional, Mitsuke, K., additional, Mitsumoto, R., additional, Miyahara, T., additional, Miyamae, T., additional, Miyamoto, N., additional, Miyauchi, H., additional, Mizokawa, T., additional, Morgan, H., additional, Mori, I., additional, Mori, T., additional, Morin, P., additional, Morioka, Y., additional, Mosnier, J., additional, Munro, I., additional, Murakami, E., additional, Murata, T., additional, Murata, Y., additional, Muro, T., additional, Nagakura, I., additional, Nagaoka, S., additional, Nagata, T., additional, Nahon, L., additional, Nakagawa, K., additional, Nakai, I., additional, Nakai, S., additional, Nakai, Y., additional, Nakaishi, H., additional, Nakajima, N., additional, Nakamura, H., additional, Nakamura, M., additional, Nakatake, M., additional, Nakazawa, M., additional, Namatame, H., additional, Namioka, T., additional, Nanba, T., additional, Naoe, S., additional, Nasu, K., additional, Neeb, M., additional, Nenner, I., additional, Nishihara, Y., additional, Nishioka, H., additional, Niwano, M., additional, Nordgren, J., additional, Norman, D., additional, Nowak, C., additional, Nyholm, R., additional, Nylén, H., additional, Ogasawara, H., additional, Ogata, T., additional, Oh, S., additional, Ohara, J., additional, Ohashi, H., additional, Ohchi, T., additional, Ohmori, K., additional, Ohnishi, A., additional, Ohno, N., additional, Ohta, T., additional, Oji, H., additional, Okada, K., additional, Okajima, T., additional, Okane, T., additional, Okuda, T., additional, Okunishi, M., additional, Okusawa, M., additional, Olson, C., additional, Onellion, M., additional, Ono, I., additional, Ono, K., additional, Onsgaard, J., additional, Onuki, H., additional, Oshima, M., additional, Ouchi, I., additional, Ouchi, Y., additional, Oura, M., additional, Park, C., additional, Park, S., additional, Perera, R., additional, Petroff, Y., additional, Poliakoff, E., additional, Pong, W., additional, Prabhakaran, K., additional, Pratt, R., additional, Qvarford, M., additional, Rader, O., additional, Rahn, S., additional, Randall, K., additional, Reininger, R., additional, Rosenberg, R., additional, Rubensson, J., additional, Sainctavit, P., additional, Saito, N., additional, Saito, T., additional, Saitoh, T., additional, Saitoh, Y., additional, Sakamoto, K., additional, Sakano, M., additional, Sakisaka, Y., additional, Samson, J., additional, Sarma, D., additional, Sasaki, T., additional, Sasano, T., additional, Sato, H., additional, Sato, N., additional, Sato, S., additional, Sato, Y., additional, Savchenko, E., additional, Schattke, W., additional, Schlachter, F., additional, Schmidt, V., additional, Schwentner, N., additional, Seki, K., additional, Sekiguchi, T., additional, Sekitani, T., additional, Sekiyama, A., additional, Seno, H., additional, Shafi, M., additional, Sham, T., additional, Sheng, L., additional, Shi, C., additional, Shidara, T., additional, Shigemasa, E., additional, Shimada, H., additional, Shimada, K., additional, Shimamura, I., additional, Shimizu, Y., additional, Shimoyama, I., additional, Shin, S., additional, Shiraga, H., additional, Shirai, M., additional, Shishidou, T., additional, Shmaenok, L., additional, Shobatake, K., additional, Simon, M., additional, Smith, N., additional, Soda, K., additional, Solov'yov, A., additional, Sonntag, B., additional, Spanke, D., additional, Stankevitch, V., additional, Steinberger, I., additional, Steiner, P., additional, Suga, S., additional, Sugawara, H., additional, Sutherland, D., additional, Suzuki, I., additional, Suzuki, M., additional, Suzuki, N., additional, Suzuki, S., additional, Suzuki, T., additional, Taguchi, Y., additional, Takahashi, N., additional, Takahashi, T., additional, Takakuwa, Y., additional, Takata, Y., additional, Takatsuchi, K., additional, Takeichi, A., additional, Takenaka, H., additional, Takizawa, Y., additional, Tanaka, A., additional, Tanaka, K., additional, Tanaka, M., additional, Tanaka, S., additional, Tanaka, T., additional, Tang, J., additional, Tani, K., additional, Taniguchi, M., additional, Tayu, T., additional, Terada, S., additional, Terminello, L., additional, Tezuka, H., additional, Tezuka, Y., additional, Thissen, R., additional, Tinone, M., additional, Tokue, I., additional, Tonner, B., additional, Toyota, E., additional, Troussel, P., additional, Ueda, K., additional, Ueda, Y., additional, Ueno, N., additional, Uhrberg, R., additional, Ukai, M., additional, Umehara, T., additional, Uozumi, T., additional, Urisu, T., additional, Vaeterlein, P., additional, Van der Laan, G., additional, Van Hove, M., additional, Viane, P., additional, Voss, J., additional, Wang, X., additional, Watanabe, M., additional, Watanabe, N., additional, Watanabe, Y., additional, Weaver, J., additional, West, J., additional, van Wezenbeek, E., additional, Whitfield, S., additional, Woodruff, D., additional, Wu, L., additional, Wu, R., additional, Xu, P., additional, Xu, W., additional, Yagi, K., additional, Yagi, S., additional, Yagishita, A., additional, Yamada, T., additional, Yamakawa, T., additional, Yamamoto, H., additional, Yamamoto, M., additional, Yamamoto, Y., additional, Yamanaka, T., additional, Yamanouchi, K., additional, Yamashita, K., additional, Yanagihara, M., additional, Yang, S., additional, Yang, Y., additional, Yeom, H., additional, Yimagawa, M., additional, Ynzunza, R., additional, Yokoya, T., additional, Yokoyama, T., additional, Yoshida, A., additional, Yoshida, H., additional, Yoshi, K., additional, Yoshimura, D., additional, Yuri, M., additional, Zama, T., additional, Zeitoun, P., additional, Zhang, X., additional, Zhang, Y., additional, Zimmerer, G., additional, and Zimmermann, R., additional
- Published
- 1996
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5. FINE STRUCTURE OF MYCOBACTERIAL CELL
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Takeya, K., primary, Koike, M., additional, Hisatsune, K., additional, Hagiwara, Y., additional, and Inoue, Y., additional
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- 1962
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6. Source contribution of black carbon aerosol during 2020-2022 at an urban site in Indo-Gangetic Plain.
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Malik A, Aggarwal SG, Kondo Y, Kumar B, Patel P, Sinha PR, Oshima N, Ohata S, Mori T, Koike M, Singh K, Soni D, and Takami A
- Abstract
The extensive emissions of black carbon (BC) from the Indo-Gangetic Plain (IGP) region of India have been well recognized. Particularly, biomass emissions from month-specific crop-residue burning (April, May, October, November) and heating activities (December-February) are considered substantial contributors to BC emissions in the IGP. However, their precise contribution to ambient BC aerosol has not been quantified yet and remains an issue of debate. Therefore, this study aims to fill this gap by quantifying the contribution of these month-specific biomass emissions to ambient BC at an urban site in IGP. This study presents the analysis of BC mass concentrations (M
BC ) measured for 3 years (2020-2022) in Delhi using an optical photometer i.e., continuous soot monitoring system (COSMOS). A statistical analysis of monthly mean MBC and factors affecting the MBC (ventilation coefficients, air mass back trajectories, fire counts) is performed to derive month-wise contribution due to background concentration, conventional emission, regional transport, crop-residue burning, and heating activities. The yearly mean MBC (5.3 ± 4.7, 5.6 ± 5.0, and 5.3 ± 3.5 μg m-3 during 2020, 2021, and 2022, respectively) remained relatively consistent with repetitive monthly patterns in each year. The peak concentrations were observed from November to January and low concentrations from June to September. Anthropogenic activities contributed significantly to MBC over Delhi with background concentration contributing only 30 % of observed MBC. The percentage contribution of emissions from crop-residue burning varied from 15 % (May) to 37 % (November), while the contribution from heating activities ranged from 25 % (December) to 39 % (January). This source quantification study highlights the significant impact of month-specific biomass emissions in the IGP and can play a vital role in better management and control of these emissions in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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7. Genome-wide screening for regulators of degradation of insulin secretory granules with a fluorescent reporter.
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Kanai A, Nishida Y, Iwamoto T, Yokota M, Aoyama S, Ueki K, Ito M, Uzawa H, Iida H, Koike M, and Watada H
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- Insulin Secretion, Membrane Proteins metabolism, Coloring Agents metabolism, Secretory Vesicles metabolism, Cytoplasmic Granules metabolism, Insulin metabolism, Insulin-Secreting Cells metabolism
- Abstract
Insulin is essential in controlling blood glucose levels, and its synthesis and secretion have been well investigated. In contrast, how insulin secretory granules (ISGs) are degraded in pancreatic beta cells remains largely unknown. To clarify the mechanism, we constructed a fluorescent reporter detecting ISG degradation, where EGFP and mCherry are tandemly conjugated to a cytoplasmic region of ZnT8, an ISG membrane-localized protein. Depletion of serum and amino acid stimulated lysosomal ISG degradation detected with the reporter. Next, with MIN6 cells expressing Cas9 and the reporter, we investigated the involvement of conventional Atg5/7-dependent autophagy to show that it is dispensable for the ISG degradation process. Finally, we performed genome-wide screening by enriching the cells lacking the ISG degradation and showed that pathways regulating autophagy are not identified. These results suggest that alternative degradation in lysosomes, instead of conventional autophagy, may be involved in ISG degradation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yuya Nishida reports financial support was provided by Japan Society for the Promotion of Science. Hirotaka Watada reports financial support was provided by Japan Society for the Promotion of Science. Masato Koike reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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8. Physical and chemical properties of PM 1 in Delhi: A comparison between clean and polluted days.
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Malik A, Aggarwal SG, Kunwar B, Deshmukh DK, Shukla K, Agarwal R, Singh K, Soni D, Sinha PR, Ohata S, Mori T, Koike M, Kawamura K, and Kondo Y
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- Environmental Monitoring, Seasons, Aerosols analysis, Carbon analysis, Soot analysis, India, Particulate Matter analysis, Air Pollutants analysis
- Abstract
Considering the significance of PM
1 aerosol in assessing health impacts of air pollution, an extensive analysis of PM1 samples collected at an urban site in Delhi is presented in this study. Overall, PM1 contributed to about 50 % of PM2.5 mass which is alarming especially in Delhi where particle mass loadings are usually higher than prescribed limits. Major portion of PM1 consisted of organic matter (OM) that formed nearly 47 % of PM1 mass. Elemental carbon (EC) contributed to about 13 % of PM1 mass, whereas SO4 2- (16 %), NH4 + (10 %), NO3 - (4 %) and Cl- (3 %) were the major inorganic ions present. Sampling was performed in two distinctive campaign periods (in terms of meteorological conditions and heating (fire) activities), during the year 2019, each spanning two-week time, i.e. (i) September 3rd -16th (clean days), and (ii) November 22nd and BC during clean days (polluted days) were 70.6 ± 26.9 and 3.9 ± 1.0 μg mth (196 ± 104 and 7.6 ± 4.1 μg m2.5 ), respectively, which were systematically lower (higher) than that of the annual mean (taken from studies conducted at same site in 2019) of 142 and 5.7 μg m2.5 and BC during clean days (polluted days) were 70.6 ± 26.9 and 3.9 ± 1.0 μg m-3 (196 ± 104 and 7.6 ± 4.1 μg m-3 ), respectively, which were systematically lower (higher) than that of the annual mean (taken from studies conducted at same site in 2019) of 142 and 5.7 μg m-3 , respectively. Changes in characteristic ratios (i.e., organic carbon (OC)/elemental carbon (EC) and K+ /EC) of chemical species detected in PM1 show an increase in biomass emissions during polluted days. Increase in biomass emission can be attributed to increase in heating practices (burning of biofuels such as wood logs, straw, and cow-dung cake) in- and around- Delhi because of fall in temperature during second campaign. Furthermore, a significant increase in NO3 - fraction of PM1 is observed during second campaign which shows fog processing of NOX due to conducive meteorological conditions in winters. Also, comparatively stronger correlation of NO3 - with K+ during second campaign (r = 0.98 as compared to r = 0.5 during first campaign) suggests the increased heating practices to be a contributing factor for increased fraction of NO3 - in PM1 . We observed that during polluted days, meteorological parameters such as dispersion rate also played a major role in intensifying the impact of increased local emissions due to heating activities. Apart from this, change in the direction of regional emission transport to study site and the topology of Delhi are the possible reasons for the elevated pollution level, especially PM1 during winter in Delhi. This study also suggests that black carbon measurement techniques used in current study (optical absorbance with heated inlet and evolved carbon techniques) can be used as reference techniques to determine the site-specific calibration constant of optical photometers for urban aerosol., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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9. Preferential arborization of dendrites and axons of parvalbumin- and somatostatin-positive GABAergic neurons within subregions of the mouse claustrum.
- Author
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Takahashi M, Kobayashi T, Mizuma H, Yamauchi K, Okamoto S, Okamoto K, Ishida Y, Koike M, Watanabe M, Isa T, and Hioki H
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- Mice, Animals, Axons metabolism, GABAergic Neurons metabolism, Somatostatin metabolism, Dendrites metabolism, Parvalbumins metabolism, Claustrum metabolism
- Abstract
The claustrum coordinates the activities of individual cortical areas through abundant reciprocal connections with the cerebral cortex. Although these excitatory connections have been extensively investigated in three subregions of the claustrum-core region and dorsal and ventral shell regions-the contribution of GABAergic neurons to the circuitry in each subregion remains unclear. Here, we examined the distribution of GABAergic neurons and their dendritic and axonal arborizations in each subregion. Combining in situ hybridization with immunofluorescence histochemistry showed that approximately 10% of neuronal nuclei-positive cells expressed glutamic acid decarboxylase 67 mRNA across the claustral subregions. Approximately 20%, 30%, and 10% of GABAergic neurons were immunoreactive for parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal polypeptide, respectively, in each subregion, and these neurochemical markers showed little overlap with each other. We then reconstructed PV and SOM neurons labeled with adeno-associated virus vectors. The dendrites and axons of PV and SOM neurons were preferentially localized to their respective subregions where their cell bodies were located. Furthermore, the axons were preferentially extended in a rostrocaudal direction, whereas the dendrites were relatively isotropic. The present findings suggest that claustral PV and SOM neurons might execute information processing separately within the core and shell regions., Competing Interests: Declarations of interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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10. Transcatheter arterial embolization of abnormal neovessels in a swine model of knee arthritis.
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Kamisako A, Ikoma A, Koike M, Makitani K, Fukuda K, Higashino N, Shibuya M, Okuno Y, Minamiguchi H, and Sonomura T
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- Animals, Female, Humans, Pain, Papain, Swine, Embolization, Therapeutic, Osteoarthritis, Knee therapy, Synovitis
- Abstract
Background: In recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees., Methods: Knee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically., Results: ANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups., Conclusion: SGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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11. Leaf uptake of atmospheric monocyclic aromatic hydrocarbons depends on plant species and compounds.
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Tani A, Koike M, Mochizuki T, and Yamane M
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- Anisoles, Benzaldehydes, Benzyl Alcohols, Phenols, Plant Leaves chemistry, Plants, Toluene analysis, Benzene analysis, Hydrocarbons, Aromatic
- Abstract
Large amounts of monocyclic aromatic hydrocarbons (MAHs) are emitted into the atmosphere, but it is unclear which compounds among MAHs are effectively removed by the above-ground parts of plants. Although fumigation experiments of MAHs at unrealistically high concentrations (~ppmv) have been conducted, experiments with ambient concentrations have scarcely been conducted. In the present study, MAHs, including benzene, toluene, phenol, benzaldehyde, and benzyl alcohol, with concentrations ranging from several to several tens ppbv, were individually fumigated to four plant species, and the uptake was monitored using proton-transfer-reaction mass spectrometry and gas chromatography-mass spectrometry. No detectable uptake was observed for benzene and toluene, but phenol, benzaldehyde, and benzyl alcohol were significantly taken up by the plants. The uptake rate normalized to fumigated concentration varied from 3 to 50 mmol m
-2 s-1 during the light period, depending on light intensity and compounds. The difference in uptake capability may be attributed not only to different metabolic activities but also to different values of Henry's law constant, which regulates the partitioning of these compounds into the liquid phase in leaves. The uptake of phenol, benzaldehyde, and benzyl alcohol was affected by stomatal conductance, suggesting that stomatal opening is the main factor regulating the uptake of the three MAHs. This is the first observation that anisole is emitted when phenol is fumigated to Spathiphyllum clevelandii, suggesting that phenol is methylated to anisole within plant leaves. Anisole is more volatile than phenol, meaning that methylation enhances the emission of xenobiotics into the atmosphere by converting them to more volatile compounds. This conversion ratio decreased with an increase in phenol concentration (from 1.3 to 143 ppbv). Considering low reaction rate coefficient of anisole with OH radicals and low conversion ratio from phenol to anisole, it is concluded that plants act to effectively remove oxygenated MAHs from the atmosphere., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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12. Anti-Inflammatory Effects of Potassium Iodide on SDS-Induced Murine Skin Inflammation.
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Hayashi S, Ishikawa S, Ishii E, Koike M, Kaminaga T, Hamasaki Y, Sairenchi T, Kobashi G, and Igawa K
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- Animals, Cytokines genetics, Dermatitis immunology, Dermatitis pathology, Female, Interleukin-10 physiology, Interleukins physiology, Mice, Mice, Inbred BALB C, Potassium Iodide therapeutic use, Sodium Dodecyl Sulfate pharmacology, Anti-Inflammatory Agents pharmacology, Dermatitis drug therapy, Potassium Iodide pharmacology
- Abstract
Potassium iodide (KI), initially derived from seaweed in the early 19th century, is used for treating sporotrichosis in dermatological practice. KI has also been used to treat several noninfectious inflammatory skin diseases. However, the mechanisms underlying the improvement in such skin diseases remain unknown, and KI is not used widely. Thus, although KI is an old drug, physicians may not prescribe it frequently because they lack knowledge about it. Although KI is very inexpensive and causes few side effects, it has been superseded by new powerful and expensive drugs, such as biological agents. We applied 3% KI topically to areas of inflammation induced by SDS in mice. The levels of IL-1 and TNF-α gene expression were reduced, whereas that of IL-10 gene expression was increased. Small interfering RNA that was designed to reduce IL-10 gene expression levels was injected into the same mice, and the anti-inflammatory effects of KI were not observed. Thus, the pharmacologic action of KI is based on its anti-inflammatory effects caused by the increase in IL-10 levels. This information would increase dermatologists' awareness of KI as an efficacious and cost-effective treatment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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13. Unique synaptic topography of crest-type synapses in the interpeduncular nucleus.
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Parajuli LK, Wako K, Maruo S, Kakuta S, and Koike M
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- Animals, Axons ultrastructure, Dendrites ultrastructure, Mice, Inbred C57BL, Microscopy, Electron, Scanning, Interpeduncular Nucleus ultrastructure, Synapses ultrastructure
- Abstract
Neurons in the central nervous system display a great diversity of synaptic architecture. While much of our knowledge on the excitatory synapse morphology derives from the prototypical asymmetric synapses, little has been studied about the atypical crest-type synapse that exists in the restricted brain regions. Here, we used focused ion beam scanning electron microscopy (FIB/SEM) to image a neuropil volume of interpeduncular nucleus (IPN) and manually reconstructed several dendrites to obtain an insight about the topography and quantitative features of crest synapses. Three-dimensional reconstruction showed numerous U-shaped structures protruding from the IPN dendrites. On either faces of the U-shaped structure, a pair of crest synapses are aligned in parallel such that there exists a positive correlation between the postsynaptic density (PSD) area of synapses that participate in pair formation. Interestingly, mitochondria are excluded from the site of crest synapses. Several presynaptic axons run through the hollow, cylindrical space of the U-shape grooves such that the plasma membrane of the axon and the dendrite are organized in a tight opposition without any intervening glial membrane. Unlike the peculiar dendritic morphology, IPN neurons possess typical somatic morphology with an oval, centrally located nucleus. In conclusion, our data reveals a hitherto unknown unique topographical feature of crest synapses in the IPN., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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14. Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens.
- Author
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Sonohara F, Yamada S, Takami H, Hayashi M, Kanda M, Tanaka C, Kobayashi D, Nakayama G, Koike M, Fujiwara M, Fujii T, and Kodera Y
- Subjects
- Adult, Aged, Aged, 80 and over, Chemotherapy, Adjuvant, Feasibility Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pancreatic Neoplasms blood supply, Pancreatic Neoplasms diagnosis, Prognosis, Retrospective Studies, Antineoplastic Agents therapeutic use, Mesenteric Arteries surgery, Neoplasm Staging, Pancreatectomy methods, Pancreatic Neoplasms therapy, Vascular Surgical Procedures methods
- Abstract
Introduction: In this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR., Methods: Between 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis., Results: Among 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002)., Conclusion: This study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
- Published
- 2019
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15. Biological and conditional factors should be included when defining criteria for resectability for patients with pancreatic cancer.
- Author
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Kato Y, Yamada S, Tashiro M, Sonohara F, Takami H, Hayashi M, Kanda M, Kobayashi D, Tanaka C, Nakayama G, Koike M, Fujiwara M, and Kodera Y
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers analysis, Carcinoma, Pancreatic Ductal diagnostic imaging, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Cholangiopancreatography, Endoscopic Retrograde, Female, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Invasiveness, Pancreatectomy, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Prognosis, Retrospective Studies, Survival Rate, Carcinoma, Pancreatic Ductal surgery, Guidelines as Topic, Pancreatic Neoplasms surgery, Patient Selection
- Abstract
Background: This study aimed to evaluate novel resectability criteria for pancreatic ductal adenocarcinoma (PDAC) proposed by the International Association of Pancreatology (IAP) by comparing them with the National Comprehensive Cancer Network (NCCN) guidelines., Methods: 369 patients who underwent upfront surgery for PDAC were retrospectively analyzed. Overall survival (OS) of each group as defined by either of the guidelines were compared and preoperative prognostic factors for OS were identified., Results: Based on the IAP-criteria, 157 patients were classified as resectable (R), 192 as borderline resectable (BR) and 20 as unresectable (UR), with the median survival time (MST) of 40 months, 17 and 11, respectively. In contrast to the NCCN-criteria, BR demonstrated significantly better OS than UR (P = 0.023) under the IAP-criteria. Performance status ≥2 (hazard ratio [HR]: 2.47, P = 0.014) and lymph node metastasis suspected by imaging (HR: 1.55, P = 0.003) were identified as independent prognostic factors by the multivariate analysis along with portal or arterial invasion, while carbohydrate antigen 19-9 ≥ 500 U/ml was not (HR: 1.23, P = 0.190)., Conclusion: The IAP-criteria, which includes biological and conditional factors, resulted in superior separation of survival curves stratified by the resectablity when compared with the NCCN-criteria., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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16. Cathepsin L-deficiency enhances liver regeneration after partial hepatectomy.
- Author
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Sato T, Yamashina S, Izumi K, Ueno T, Koike M, Ikejima K, Peters C, and Watanabe S
- Subjects
- Animals, Autophagy, Cathepsin L metabolism, Cathepsins, Cells, Cultured, Hepatectomy, Liver, Lysosomes, Male, Mice, Mice, Knockout, NF-E2-Related Factor 2, Proteolysis, Receptors, Notch, Signal Transduction, Transcription Factor TFIIH, Transcription Factors, Cathepsin L deficiency, Liver Regeneration physiology
- Abstract
Aim: Cathepsin L (Ctsl) plays a pivotal role in lysosomal and autophagic proteolysis. Previous investigations revealed that partial hepatectomy (PH) decreases biosynthesis of cathepsins in liver, followed by suppression of lysosomal and autophagic proteolysis during liver regeneration. Conversely, it was reported that autophagy-deficiency suppressed liver regeneration. Thus, the purpose of this study is to determine if Ctsl deficiency affects liver regeneration after PH., Methods: 70% of PH was performed in male Ctsl-deficient mice (Ctsl-/-) and wild-type littermates (Ctsl +/+) after PH. Mice were sacrificed and wet weight of the whole remaining liver was measured. Bromodeoxyuridine (BrdU)-immunostaining of liver sections was performed. Expression of cyclin D1, p62, LC-3, Nrf2, cleaved-Notch1, Hes1 was evaluated by western blot analysis. NQO1 mRNA expression was measured by realtime-PCR., Results: After a 70% of PH, the liver mass was significantly restored within 5 days in Ctsl-/- mice compared to wild-type. Ctsl-deficiency enhanced the increases in both the rate of BrdU-positive cells and cyclin D1 expression after PH more than wild-type mice. On the other hand, Ctsl-deficiency upregulated p62, cleaved-Notch1 and Hes1 expression after PH. Moreover, the protein level of Nrf2 in the nucleus and mRNA expression of NQO1 in the liver after PH was also up-regulated in Ctsl-/- mice., Conclusions: These findings suggest that accumulation of p62 due to loss of Ctsl plays an important role in liver regeneration through activation of Nrf2-Notch1 signaling. Taken together, Ctsl might be a new therapeutic target on disorder of liver regeneration., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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17. Purkinje Cells Are More Vulnerable to the Specific Depletion of Cathepsin D Than to That of Atg7.
- Author
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Koike M, Shibata M, Sunabori T, Yamaguchi J, Sakimura K, Komatsu M, Tanaka K, and Uchiyama Y
- Subjects
- Animals, Autophagy, Autophagy-Related Protein 7 metabolism, Axons metabolism, Axons ultrastructure, Cathepsin D metabolism, Central Nervous System metabolism, Central Nervous System ultrastructure, Immunohistochemistry, Lysosomes metabolism, Lysosomes ultrastructure, Male, Mice, Neuronal Ceroid-Lipofuscinoses metabolism, Neuronal Ceroid-Lipofuscinoses pathology, Neurons metabolism, Neurons ultrastructure, Phagosomes metabolism, Phagosomes ultrastructure, Purkinje Cells metabolism, Purkinje Cells pathology, Purkinje Cells ultrastructure, Autophagy-Related Protein 7 genetics, Cathepsin D genetics, Neuronal Ceroid-Lipofuscinoses genetics
- Abstract
Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the maintenance of metabolism in central nervous system neurons. To further understand the role of CTSD in central nervous system neurons, we generated mice with a CTSD deficiency specifically in the Purkinje cells (PCs) (CTSD
Flox/Flox ;GRID2-Cre) and compared their phenotypes with those of PC-selective Atg7-deficient (Atg7Flox/Flox ;GRID2-Cre) mice. In both strains of mice, PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly than their Atg7-deficient counterparts. When CTSD-deficient PCs died, the neuronal cell bodies became shrunken, filled with autophagosomes and autolysosomes, and had nuclei with dispersed small chromatin fragments. The dying Atg7-deficient PCs also showed similar ultrastructures, indicating that the neuronal cell death of CTSD- and Atg7-deficient PCs was distinct from apoptosis. Immunohistochemical observations showed the formation of calbindin-positive axonal spheroids and the swelling of vesicular GABA transporter-positive presynaptic terminals that were more pronounced in Atg7-deficient PCs than in CTSD-deficient PCs. An accumulation of tubular vesicles may have derived from the smooth endoplasmic reticulum; nascent autophagosome-like structures with double membranes was a common feature in the swollen axons of these PCs. These results suggested that PCs were more vulnerable to CTSD deficiency in lysosomes than to autophagy impairment, and this vulnerability does not depend on the severity of axonal swelling., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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18. Lysosomal Storage of Subunit c of Mitochondrial ATP Synthase in Brain-Specific Atp13a2-Deficient Mice.
- Author
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Sato S, Koike M, Funayama M, Ezaki J, Fukuda T, Ueno T, Uchiyama Y, and Hattori N
- Subjects
- Adenosine Triphosphatases metabolism, Animals, Brain enzymology, Brain pathology, Cathepsin D metabolism, Disease Models, Animal, Female, Gene Knockout Techniques, Humans, Lipofuscin metabolism, Lysosomes enzymology, Lysosomes pathology, Membrane Proteins metabolism, Mice, Mice, Inbred C57BL, Mitochondrial Proton-Translocating ATPases genetics, Mutation, Neuronal Ceroid-Lipofuscinoses enzymology, Neuronal Ceroid-Lipofuscinoses genetics, Neuronal Ceroid-Lipofuscinoses pathology, Organ Specificity, Parkinson Disease enzymology, Parkinson Disease pathology, Parkinsonian Disorders enzymology, Parkinsonian Disorders pathology, Proton-Translocating ATPases metabolism, Adenosine Triphosphatases genetics, Membrane Proteins genetics, Mitochondrial Proton-Translocating ATPases metabolism, Parkinson Disease genetics, Parkinsonian Disorders genetics, Proton-Translocating ATPases genetics
- Abstract
Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid lipofuscinosis, including accumulation of lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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19. Suppression of Ischemia-Induced Hippocampal Pyramidal Neuron Death by Hyaluronan Tetrasaccharide through Inhibition of Toll-Like Receptor 2 Signaling Pathway.
- Author
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Sunabori T, Koike M, Asari A, Oonuki Y, and Uchiyama Y
- Subjects
- Animals, Cell Death, Disease Models, Animal, Hippocampus metabolism, Hippocampus pathology, Hyaluronic Acid chemistry, Immunohistochemistry, In Situ Nick-End Labeling, Mice, Neuroprotective Agents, Polymerase Chain Reaction, Pyramidal Cells metabolism, Signal Transduction drug effects, Hyaluronic Acid pharmacology, Hypoxia-Ischemia, Brain metabolism, Hypoxia-Ischemia, Brain pathology, Pyramidal Cells pathology, Toll-Like Receptor 2 metabolism
- Abstract
Toll-like receptors (TLRs) are one of the main contributors that induce inflammation under tissue injury and infection. Because excessive inflammation can aggravate disease states, it is important to control inflammation at a moderate level. Herein, we show that hyaluronan (HA) oligomer, HA tetrasaccharide (HA4), could suppress the expression of proinflammatory cytokine IL-1β when stimulated with both TLR2- and TLR4-specific agonists in primary hippocampal neurons. To understand the effect of HA4 against ischemic insult, we performed hypoxic-ischemic (H/I) brain injury against neonatal mice. HA4 treatment significantly prevented hippocampal pyramidal cell death even 7 days after H/I injury, compared with the control mice. Although TLR2 and TLR4 are known as receptors for HA and also act as a receptor for inducing inflammation, only TLR2-deficient mice showed tolerance against H/I injury. Moreover, HA4 administration suppressed gliosis by inhibiting the activation of NF-κB, the downstream target of TLR2, which led to the suppression of IL-1β expression. Taken together, our data suggest that the neuroprotective effect of HA4 relies on antagonizing the TLR2/NF-κB pathway to reduce inflammation through suppressing the expression of proinflammatory cytokines after neonatal H/I brain injury., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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20. Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation.
- Author
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Yamada D, Saiki S, Furuya N, Ishikawa K, Imamichi Y, Kambe T, Fujimura T, Ueno T, Koike M, Sumiyoshi K, and Hattori N
- Subjects
- Animals, Cell Line, Tumor, Dose-Response Relationship, Drug, HeLa Cells, Humans, Lysosomes drug effects, Lysosomes ultrastructure, Metabolic Clearance Rate drug effects, Phagosomes drug effects, Phagosomes ultrastructure, Rats, Antitubercular Agents administration & dosage, Ethambutol administration & dosage, Lysosomes physiology, Phagosomes physiology, Zinc pharmacokinetics
- Abstract
Ethambutol is a common medicine used for the treatment of tuberculosis, which can have serious side effects, such as retinal and liver dysfunction. Although ethambutol has been reported to impair autophagic flux in rat retinal cells, the precise molecular mechanism remains unclear. Using various mammalian cell lines, we showed that ethambutol accumulated in autophagosomes and vacuolated lysosomes, with marked Zn(2+) accumulation. The enlarged lysosomes were neutralized and were infiltrated with Zn(2+) accumulations in the lysosomes, with simultaneous loss of acidification. These results suggest that EB neutralizes lysosomes leading to insufficient autophagy, implying that some of the adverse effects associated with EB in various organs may be of this mechanism., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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21. An idiopathic azygos vein aneurysm mimicking a mediastinal mass.
- Author
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Ichiki Y, Hamatsu T, Suehiro T, Koike M, Tanaka F, and Sugimachi K
- Subjects
- Aged, Aneurysm surgery, Diagnosis, Differential, Humans, Magnetic Resonance Imaging, Male, Tomography, X-Ray Computed, Aneurysm diagnosis, Azygos Vein, Mediastinal Diseases diagnosis, Thoracic Surgery, Video-Assisted methods, Vascular Surgical Procedures methods
- Abstract
Azygos vein aneurysms are very rare causes of mediastinal masses and are usually accidental findings on chest roentgenography. Most are detected in patients with portal hypertension or venous malformations. An idiopathic azygos vein aneurysm is assumed to be congenital and is much more exceptional. We present the case of a 76-year-old man who underwent excision of an idiopathic azygos vein aneurysm by video-assisted thoracoscopic surgery (VATS)., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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22. Combined multi-kernel chest computed tomography images optimized for depicting both lung and soft tissue.
- Author
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Takagi S, Nagase H, Hayashi T, Kita T, Hayashi K, Sanada S, and Koike M
- Subjects
- Adult, Aged, Aged, 80 and over, Artifacts, Female, Humans, Male, Middle Aged, Observer Variation, Radiographic Image Interpretation, Computer-Assisted, Radiology methods, Retrospective Studies, Image Processing, Computer-Assisted methods, Lung diagnostic imaging, Radiography, Thoracic, Tomography, X-Ray Computed
- Abstract
Purpose: To evaluate the quality of our improved multi-kernel chest computed tomography (CT) images., Methods: A random sample of 50 normal patients was retrospectively selected from those who underwent chest CT scans between January 2010 and July 2010. Normal lung structures were divided into six categories, and two radiologists independently compared with lung images., Results: The improved multi-kernel images were displayed identically to soft tissue images on soft tissue window settings and were evaluated as equal to lung images on lung window settings., Conclusions: This improved multi-kernel technique required fewer stored images and simplified examinations of chest CT., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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23. Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice.
- Author
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Bombo RP, Afonso MS, Machado RM, Lavrador MS, Nunes VS, Quintão ER, Koike M, Catanozi S, Lin CJ, Nakandakare ER, and Lottenberg AM
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 1, ATP-Binding Cassette Transporters metabolism, Absorption, Animals, Aorta pathology, Atherosclerosis pathology, Body Weight, CD36 Antigens metabolism, Cholesterol metabolism, Feeding Behavior, Lipids blood, Lipoproteins metabolism, Macrophages metabolism, Macrophages, Peritoneal metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phytosterols blood, Scavenger Receptors, Class E metabolism, Arteries pathology, Atherosclerosis prevention & control, Phytosterols chemistry, Receptors, LDL genetics
- Abstract
Scope: There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development., Methods and Results: Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10). Plasma and arterial wall cholesterol and PS concentrations, lesion area, macrophage infiltration, and mRNA expression from LOX-1, CD36, ABCA1 and ABCG1 in peritoneal macrophages were measured. After 16 weeks, the plasma cholesterol concentration in PS mice was lower than that in the controls (p = 0.02) and in the arterial wall (p = 0.03). Plasma PS concentrations were higher in PS-fed animals than in controls (p < 0.0001); however, the arterial wall PS concentration did not differ between groups. The atherosclerotic lesion area in the PS group (n = 5) was smaller than that in controls (p = 0.0062) and the macrophage area (p = 0.0007). PS correlates negatively with arterial lipid content and macrophage (r = -0.76; p < 0.05). PS supplementation induced lower ABCG1 mRNA expression (p < 0.05)., Conclusions: Despite inducing an increase in PS plasma concentration, PS supplementation is not associated with its accumulation in the arterial wall and prevents atherosclerotic lesion development., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
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24. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation.
- Author
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Koike M, Yutoku Y, and Koike A
- Subjects
- Animals, CHO Cells, Cricetinae, Cricetulus, Protein Structure, Tertiary, Structure-Activity Relationship, Cell Nucleus physiology, Cell Nucleus radiation effects, DNA Damage physiology, Rad52 DNA Repair and Recombination Protein chemistry, Rad52 DNA Repair and Recombination Protein metabolism
- Abstract
Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1-418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1-418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1-418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1-418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411-418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is important for the physiological function of Rad52 not only at a late stage following irradiation, but also at an early stage., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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25. Resveratrol affects undifferentiated and differentiated PC12 cells differently, particularly with respect to possible differences in mitochondrial and autophagic functions.
- Author
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Hayakawa N, Shiozaki M, Shibata M, Koike M, Uchiyama Y, Matsuura N, and Gotow T
- Subjects
- AMP-Activated Protein Kinases genetics, AMP-Activated Protein Kinases metabolism, Animals, Cell Differentiation, Gene Expression Regulation drug effects, Mitochondria metabolism, Mitochondria ultrastructure, Mitochondrial Proton-Translocating ATPases genetics, Mitochondrial Proton-Translocating ATPases metabolism, Neurites drug effects, PC12 Cells, Rats, Resveratrol, Sirtuin 1 genetics, Sirtuin 1 metabolism, Superoxide Dismutase genetics, Superoxide Dismutase metabolism, Autophagy drug effects, Mitochondria drug effects, Stilbenes pharmacology
- Abstract
Since resveratrol is considered to exert a unique dual effect, protective for normal cells but toxic to tumor cells, its action on undifferentiated (original) and differentiated PC12 cells was analyzed, because undifferentiated cells are tumorigenic and differentiated ones are neuronal in nature. Compared to resveratrol-untreated cells in both undifferentiated and differentiated cell groups, cells treated with different doses of resveratrol, at dosages of 1, 10 and 100 μM, showed the following alterations. Dying/dead cells were significantly increased in a dose-dependent manner in undifferentiated cells, but they were unchanged at doses of up to 10 μM resveratrol in differentiated cells. In living cells, neurites were short in undifferentiated cells, but drastically elongated with an increased number in differentiated cells. The expression of SIRT1 was drastically reduced in undifferentiated cells, but stable in differentiated cells. SIRT3 was significantly enhanced in a dose-dependent manner at resveratrol doses of up to 10 μM in both cells, with reduction and more enhanced at a dosage of 100 μM in undifferentiated and differentiated cells, respectively. Mitochondrial number and ATP synthase β subunit expression was unaltered at doses of up to 10 μM and were significantly reduced at doses of 100 μM in undifferentiated cells, but they were significantly increased in a dose-dependent manner, with a slight reduction in the ATP synthase at doses of 100 μM, in differentiated cells. In a dose-dependent manner, the number of autophagosomes and the LC3-II/LC3-I ratio were significantly less in undifferentiated cells and greater in differentiated cells. Also, in a dose-dependent manner, the expression of phosphorylated AMP-activated kinase (AMPK) was significantly less in undifferentiated cells and greater in differentiated cells. Resveratrol-induced AMPK suppression and activation, possibly through the modulation of SIRT protein activity, may thus be related to the inhibition and promotion of mitochondrial and autophagic functions, leading to cell death and survival in undifferentiated and differentiated cells, respectively., (Copyright © 2012 Elsevier GmbH. All rights reserved.)
- Published
- 2013
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26. Accumulation of p21 proteins at DNA damage sites independent of p53 and core NHEJ factors following irradiation.
- Author
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Koike M, Yutoku Y, and Koike A
- Subjects
- Animals, Cell Line, Cell Line, Transformed, Cell Line, Tumor, Cricetinae, Humans, Mice, Proliferating Cell Nuclear Antigen metabolism, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA Breaks, Double-Stranded, Recombination, Genetic, Tumor Suppressor Protein p53 metabolism
- Abstract
The cyclin-dependent kinase (CDK) inhibitor p21 plays key roles in p53-dependent DNA-damage responses, i.e., cell cycle checkpoints, senescence, or apoptosis. p21 might also play a role in DNA repair. p21 foci arise at heavy-ion-irradiated DNA-double-strand break (DSB) sites, which are mainly repaired by nonhomologous DNA-end-joining (NHEJ). However, no mechanisms of p21 accumulation at double-strand break (DSB) sites have been clarified in detail. Recent works indicate that Ku70 and Ku80 are essential for the accumulation of other NHEJ core factors, e.g., DNA-PKcs, XRCC4 and XLF, and other DNA damage response factors, e.g., BRCA1. Here, we show that p21 foci arise at laser-irradiated sites in cells from various tissues from various species. The accumulation of EGFP-p21 was detected in not only normal cells, but also transformed or cancer cells. Our results also showed that EGFP-p21 accumulated rapidly at irradiated sites, and colocalized with the DSB marker γ-H2AX and with the DSB sensor protein Ku80. On the other hand, the accumulation occurred in Ku70-, Ku80-, or DNA-PKcs-deficient cell lines and in human papillomavirus 18-positive cells, whereas the p21 mutant without the PCNA-binding region (EGFP-p21(1-146)) failed to accumulate at the irradiated sites. These findings suggest that the accumulation of p21, but not functional p53 and the NHEJ core factors, is dependent on PCNA. These findings also suggest that the accumulation activity of p21 at DNA damaged sites is conserved among human and animal cells, and p21 is a useful tool as a detection marker of DNA damaged sites., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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27. Phenolic glycosides from Agrimonia pilosa.
- Author
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Kato H, Li W, Koike M, Wang Y, and Koike K
- Subjects
- Animals, Drugs, Chinese Herbal chemistry, Drugs, Chinese Herbal pharmacology, Flavones chemistry, Flavones pharmacology, Glycoside Hydrolase Inhibitors, Glycosides chemistry, Glycosides pharmacology, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Phenols chemistry, Phenols pharmacology, Rats, Stereoisomerism, Agrimonia chemistry, Drugs, Chinese Herbal isolation & purification, Flavones isolation & purification, Glycosides isolation & purification, Phenols isolation & purification
- Abstract
Phytochemical investigation of the methanolic extract from the aerial parts of Agrimonia pilosa led to the isolation of three compounds, (-)-aromadendrin 3-O-β-D-glucopyranoside, desmethylagrimonolide 6-O-β-D-glucopyranoside, and 5,7-dihydroxy-2-propylchromone 7-O-β-D-glucopyranoside, together with nine known compounds, agrimonolide 6-O-glucoside, takanechromone C, astragalin, afzelin, tiliroside, luteolin, quercetin, isoquercetrin, and quercitrin. Their structures were determined by various spectroscopic analysis and chemical transformations., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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28. Free fatty acids stimulate autophagy in pancreatic β-cells via JNK pathway.
- Author
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Komiya K, Uchida T, Ueno T, Koike M, Abe H, Hirose T, Kawamori R, Uchiyama Y, Kominami E, Fujitani Y, and Watada H
- Subjects
- Animals, Fatty Acids, Nonesterified metabolism, Fatty Acids, Nonesterified pharmacology, Insulin-Secreting Cells drug effects, Lactosylceramides metabolism, Male, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 8 antagonists & inhibitors, Palmitates pharmacology, Protein Kinase Inhibitors pharmacology, Autophagy, Insulin-Secreting Cells physiology, Mitogen-Activated Protein Kinase 8 metabolism, Palmitates metabolism
- Abstract
Recent studies have suggested that free fatty acids stimulate autophagy of pancreatic beta cells. The aim of this study was to verify the free fatty acids (FFA)-induced autophagy and investigate its molecular mechanism. As reported previously, palmitate strongly enhanced the conversion of light chain (LC)3-I to LC3-II, a marker of activation of autophagy in INS-1 beta cells. Palmitate-induced conversion of LC3-I to LC3-II was also observed in neuron-, muscle-, and liver-derived cells. In addition, palmitate induced the formation of typical autophagosomes and autolysosomes and enhanced the degradation rate of long-lived proteins. These results confirmed that palmitate activates autophagic flux in most of the cells. While FFAs reportedly activate several signal transduction pathways in beta cells, palmitate-induced autophagy was blocked by a JNK inhibitor. Although enhanced oxidative stress and endoplasmic reticulum (ER) stress are suspected to mediate FFA-induced activation of JNK1, the induction of autophagy was not associated with changes in molecular markers related to oxidative and endoplasmic reticulum stresses. On the other hand, phosphorylation of double stranded RNA-dependent protein kinase (PKR) paralleled JNK1 activation. Considered together, our study suggested that FFA stimulated functional autophagy possibly through the PKR-JNK1 pathway independent of ER or oxidative stress., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
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29. Cathepsin L in bone marrow-derived cells is required for retinal and choroidal neovascularization.
- Author
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Shimada N, Ohno-Matsui K, Iseki S, Koike M, Uchiyama Y, Wang J, Yoshida T, Sato T, Peters C, Mochizuki M, and Morita I
- Subjects
- Angiography methods, Animals, Antigens, CD metabolism, Bone Marrow Transplantation, Cadherins metabolism, Leukosialin biosynthesis, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Oxygen metabolism, Vascular Endothelial Growth Factor A metabolism, Bone Marrow Cells cytology, Cathepsin L metabolism, Choroidal Neovascularization, Retinal Neovascularization
- Abstract
Many vision-threatening diseases are characterized by intraocular neovascularization, (e.g., proliferative diabetic retinopathy and age-related macular degeneration). Although a new therapy with anti-VEGF antibodies is being used to treat these intraocular neovascular disorders, the visual recovery is limited, mainly because of the remnants of fibrovascular tissues. The ideal goal of the treatment is to prevent the invasion of new vessels into the avascular tissue through a matrix barrier. The purpose of this study was to determine the role played by cathepsin L, a matrix degrading enzyme, on intraocular angiogenesis. Used established animal models of retinal and choroidal neovascularization, we demonstrated that an inhibition of cathepsin L by specific inhibitors resulted in a significant decrease of intraocular neovascularization. A similar decrease of neovascularization was found in cathepsin L-deficient mice. Transplantation of bone marrow from cathepsin L-deficient mice into wild-type mice significantly reduced the degree of intraocular neovascularization. In addition, immunocytochemical analyses demonstrated that VE cadherin-positive endothelial progenitor cells, but not CD43-positive or Iba-1-positive cells, were the major cells contributing to the production of cathepsin L. These data indicate that cathepsin L expressed in endothelial progenitor cells plays a critical role in intraocular angiogenesis and suggest a potential therapeutic approach of targeting cathepsin L for neovascular ocular diseases.
- Published
- 2010
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30. Maintaining ATP levels via the suppression of PERK-mediated rRNA synthesis at ER stress.
- Author
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Okamoto A, Koike M, Yasuda K, and Kakizuka A
- Subjects
- HeLa Cells, Humans, Protein Kinase Inhibitors pharmacology, RNA, Ribosomal antagonists & inhibitors, Thapsigargin pharmacology, Tunicamycin pharmacology, eIF-2 Kinase antagonists & inhibitors, Adenosine Triphosphate metabolism, Endoplasmic Reticulum enzymology, RNA, Ribosomal biosynthesis, Stress, Physiological, eIF-2 Kinase metabolism
- Abstract
Currently, [(3)H]uridine is most often used to monitor rRNA synthesis in cultured cells. We show here that radiolabeled ribonucleoside triphosphates, such as [alpha-(33)P]UTP, in culture medium were also incorporated efficiently not only into cells but also into de novo RNA, particularly rRNA. Using this method, we first revealed that endoplasmic reticulum (ER) stress inducers such as tunicamycin and thapsigargin suppressed de novo rRNA synthesis, and that PERK, but not IRE1alpha or ATF6, mediated the suppression. PERK is known to mediate the suppression of de novo protein synthesis via phosphorylation of eIF2alpha. Consistently, other translational inhibitors such as PSI, proteasomal inhibitor, and cycloheximide suppressed de novo rRNA synthesis. eIF2alpha knockdown also suppressed both de novo protein and rRNA syntheses. Furthermore, ER stress reduced cellular ATP levels, and the suppression of rRNA synthesis apparently mitigated their reduction. These observations provided a close link between ATP levels and suppression of de novo rRNA synthesis at ER stress, and we proposed a novel feedback mechanism, in which ATP levels were maintained via suppression of de novo rRNA synthesis in ATP-demanding stresses, such as ER stress., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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31. LC3, a microtubule-associated protein1A/B light chain3, is involved in cytoplasmic lipid droplet formation.
- Author
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Shibata M, Yoshimura K, Tamura H, Ueno T, Nishimura T, Inoue T, Sasaki M, Koike M, Arai H, Kominami E, and Uchiyama Y
- Subjects
- Animals, Gene Knockdown Techniques, Microtubule-Associated Proteins genetics, PC12 Cells, RNA, Messenger genetics, Rats, Triglycerides metabolism, Autophagy, Cytoplasm metabolism, Lipid Metabolism, Microtubule-Associated Proteins metabolism
- Abstract
The cytoplasmic lipid droplet (LD) is one of organelles that has a neutral lipid core with a single phospholipid layer. LDs are believed to be generated between the two leaflets of the endoplasmic reticulum (ER) membrane and to play various roles, such as high effective energy storage. However, it remains largely unknown how LDs are generated and grow in the cytoplasm. We have previously shown that the Atg conjugation system that is essential for autophagosome formation is involved in LD formation in hepatocytes and cardiac myocytes. We show here that LC3 itself is involved in LD formation by using RNA interference (RNAi). All cultured cell lines examined, in which the expression of LC3 was suppressed by RNAi, showed reduced LD formation. Triacylglycerol, a major component of LDs, was synthesized and degraded in LC3 mRNA-knockdown cells as well as in control cells. Interestingly, potential of the bulk protein degradation in the knockdown-cells was also evident in the control cells. These findings indicate that LC3 is involved in the LD formation regardless of the bulk degradation, and that LC3 has two pivotal roles in cellular homeostasis mediated by autophagy and lipid metabolism., (2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
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32. Arteriovenous malformation arising on persistent sciatic vessels.
- Author
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Kuma S, Mii S, Masaki I, Koike M, and Nakahara I
- Subjects
- Adult, Arteries abnormalities, Arteriovenous Malformations diagnostic imaging, Enbucrilate administration & dosage, Female, Humans, Iodized Oil administration & dosage, Tissue Adhesives administration & dosage, Tomography, X-Ray Computed, Treatment Outcome, Arteriovenous Malformations therapy, Buttocks blood supply, Embolization, Therapeutic, Lower Extremity blood supply
- Abstract
Background: A persistent sciatic artery is a rare congenital anomaly, and an arteriovenous malformation arising on persistent sciatic vessels is extremely rare., Methods: This report presents the case of a 30-year-old female with persistent sciatic vessels complicated with an arteriovenous malformation in the right buttock. It was surgically inaccessible, and a three-staged transcatheter embolization using 20% N-butyl-cyanoacrylate/80% lipiodol was performed., Results: The arteriovenous malformation was shown to have been extinguished by multidetector computed tomography., Conclusions: This report presents the first case of persistent sciatic vessels complicated with an arteriovenous malformation treated by transcatheter embolization., (Copyright 2009. Published by Elsevier Inc.)
- Published
- 2010
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33. The MAP1-LC3 conjugation system is involved in lipid droplet formation.
- Author
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Shibata M, Yoshimura K, Furuya N, Koike M, Ueno T, Komatsu M, Arai H, Tanaka K, Kominami E, and Uchiyama Y
- Subjects
- Animals, Autophagy-Related Protein 7, Heart, Hepatocytes metabolism, Mice, Mice, Mutant Strains, Microtubule-Associated Proteins deficiency, Microtubule-Associated Proteins genetics, Phagosomes metabolism, Rats, Autophagy, Lipid Metabolism, Liver metabolism, Microtubule-Associated Proteins metabolism
- Abstract
Lipid droplets (LDs) are ubiquitous in eukaryotic cells, while excess free fatty acids and glucose in plasma are converted to triacylglycerol (TAG) and stored as LDs. However, the mechanism for the generation and growth of LDs in cells is largely unknown. We show here that the LC3 lipidation system essential for macroautophagy is involved in LD formation. LD formation accompanied by accumulation of TAG induced by starvation was largely suppressed in the hepatocytes that cannot execute autophagy. Under starvation conditions, LDs in addition to autophagosomes were abundantly formed in the cytoplasm of these tissue cells. Moreover, LC3 was localized on the surface of LDs and LC3-II (lipidation form) was fractionated to a perilipin (LD marker)-positive lipid fraction from the starved liver. Taken together, these results indicate that the LC3 conjugation system is critically involved in lipid metabolism via LD formation.
- Published
- 2009
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34. Tissue-specific DNA-PK-dependent H2AX phosphorylation and gamma-H2AX elimination after X-irradiation in vivo.
- Author
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Koike M, Sugasawa J, Yasuda M, and Koike A
- Subjects
- Animals, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins genetics, DNA-Activated Protein Kinase genetics, DNA-Binding Proteins genetics, Kidney metabolism, Kidney radiation effects, Liver metabolism, Liver radiation effects, Mice, Mice, Knockout, Nuclear Proteins genetics, Phosphorylation, Protein Serine-Threonine Kinases genetics, Skin metabolism, Skin radiation effects, Spleen metabolism, Spleen radiation effects, Tumor Suppressor Proteins genetics, X-Rays, DNA Breaks, Double-Stranded, DNA-Activated Protein Kinase metabolism, DNA-Binding Proteins metabolism, Histones metabolism, Nuclear Proteins metabolism
- Abstract
Histone H2AX rapidly undergoes phosphorylation at Ser139 (gamma-H2AX) in response to DNA double-strand breaks. Although ATM kinase and DNA-PK phosphorylate Ser139 of H2AX in culture cells, the regulatory mechanism of gamma-H2AX level remains unclear in vivo. Here, we detected the phosphorylation of H2AX and the elimination of gamma-H2AX in the mouse skin after X-irradiation. Furthermore, following X-irradiation, the level of gamma-H2AX also increased in mice lacking either ATM or DNA-PK. Although the elimination after X-irradiation was detected in the skin of these mutant mice, the elimination in DNA-PK-deficient mice was slower than that in C3H and ATM knockout mice, suggesting that a fraction of gamma-H2AX in the skin is eliminated in a DNA-PK-dependent manner. Although the DNA-PK-dependent elimination of gamma-H2AX was also detected in the liver, kidney, and spleen, the DNA-PK-dependent phosphorylation of H2AX was detected in the spleen only. These results suggest that the regulatory mechanism of gamma-H2AX level is tissue-specific.
- Published
- 2008
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- View/download PDF
35. Inefficient phagosome maturation in infant macrophages.
- Author
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Saito F, Kuwata H, Oiki E, Koike M, Uchiyama Y, Honda K, and Takeda K
- Subjects
- Age Factors, Animals, Immunity, Innate, Interferon-gamma immunology, Interferon-gamma pharmacology, Lysosomes immunology, Lysosomes microbiology, Macrophages microbiology, Macrophages ultrastructure, Mice, Mice, Inbred BALB C, Phagosomes microbiology, rab GTP-Binding Proteins metabolism, rab7 GTP-Binding Proteins, Escherichia coli Infections immunology, Macrophages immunology, Phagosomes immunology
- Abstract
The quantitative and qualitative differences between the immune systems of infants and adults have been extensively investigated in the context of adaptive immunity. Here, we demonstrate that the infantile innate immune system is immature and weak against bacterial infections. Upon infection by Escherichia coli, macrophages from infantile mice showed a lower performance in killing the bacteria. In infant macrophages, bacteria were taken up relatively normally and delivered into lysosomal compartments, but not efficiently digested. The inefficient bacterial killing in infant macrophages was correlated with impaired acidification of the lysosomal compartments and reduced lysosomal recruitment of Rab7, an essential component of the acidification process. The acidification defect was not intrinsic to the cells, and was rescued by pretreatment with interferon-gamma. Thus, we propose that the limited capacity of phagosome maturation is one of the major causes of the high sensitivity to infectious microorganisms during infancy and that the specific cytokine milieu shapes the nature of infantile innate immunity.
- Published
- 2008
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36. Participation of autophagy in renal ischemia/reperfusion injury.
- Author
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Suzuki C, Isaka Y, Takabatake Y, Tanaka H, Koike M, Shibata M, Uchiyama Y, Takahara S, and Imai E
- Subjects
- Animals, Biomarkers, Biopsy, Cell Hypoxia, Cell Line, Humans, Intracellular Membranes, Kidney metabolism, Lysosomes metabolism, Male, Mice, Mice, Inbred C57BL, Microscopy, Electron, Reperfusion Injury metabolism, Reperfusion Injury surgery, Autophagy, Kidney injuries, Reperfusion Injury pathology
- Abstract
Renal ischemia-reperfusion (I/R) injury is inevitable in transplantation, and it results in renal tubular epithelial cells undergoing cell death. We observed an increase in autophagosomes in the tubular epithelial cells of I/R-injured mouse models, and in biopsy specimens from human transplanted kidney. However, it remains unclear whether autophagy functions as a protective pathway, or contributes to I/R-induced cell death. Here, we employed the human renal proximal tubular epithelial cell line HK-2 in order to explore the role of autophagy under hypoxia (1% O(2)) or activation of reactive oxygen species (500 microM H(2)O(2)). When compared to normoxic conditions, 48h of hypoxia slightly increased LC3-labeled autophagic vacuoles and markedly increased LAMP2-labeled lysosomes. We observed similar changes in the mouse IR-injury model. We then assessed autophagic generation and degradation by inhibiting the downstream lysosomal degradation of autophagic vacuoles using lysosomal protease inhibitor. We found that autophagosomes increased markedly under hypoxia in the presence of lysosomal protease inhibitors, thus suggesting that hypoxia induces high turnover of autophagic generation and degradation. Furthermore, inhibition of autophagy significantly inhibited H(2)O(2)-induced cell death. In conclusion, high turnover of autophagy may lead to autophagic cell death during I/R injury.
- Published
- 2008
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37. Ablation of Csk in neural crest lineages causes corneal anomaly by deregulating collagen fibril organization and cell motility.
- Author
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Takatsuka A, Yagi R, Koike M, Oneyama C, Nada S, Schmedt C, Uchiyama Y, and Okada M
- Subjects
- Animals, CSK Tyrosine-Protein Kinase, Cell Movement physiology, Cornea cytology, Cornea embryology, Cornea metabolism, Fluorescence Resonance Energy Transfer, Mesoderm cytology, Mesoderm embryology, Mesoderm metabolism, Mice, Mice, Knockout, Mice, Mutant Strains, Mice, Transgenic, Myelin P0 Protein genetics, Phenotype, Promoter Regions, Genetic, Protein-Tyrosine Kinases genetics, Protein-Tyrosine Kinases physiology, RNA Interference, Retinoblastoma-Like Protein p130 metabolism, src-Family Kinases, Collagen metabolism, Cornea abnormalities, Neural Crest cytology, Neural Crest enzymology, Protein-Tyrosine Kinases deficiency
- Abstract
Src family kinases (SFKs) have been implicated in the regulation of cell motility. To verify their in vivo roles during development, we generated mutant mice in which Csk, a negative regulator of SFKs, was inactivated in neural crest lineages using the Protein zero promoter in a Cre-loxP system. Inactivation of Csk caused deformities in various tissues of neural crest origins, including facial dysplasia and corneal opacity. In the cornea, the stromal collagen fibril was disorganized and there was an overproduction of collagen 1a1 and several metalloproteases. The corneal endothelium failed to overlie the central region of the eye and the peripheral endothelium displayed a disorganized cytoskeleton. Corneal mesenchymal cells cultured from mutant mice showed attenuated cell motility. In these cells, p130 Crk-associated substrate (Cas) was hyperphosphorylated and markedly downregulated. The expression of a dominant negative Cas (Cas Delta SD) could suppress the cell motility defects. Fluorescence resonance energy transfer analysis revealed that activation of Rac1 and Cdc42 was depolarized in Csk-inactivated cells, which was restored by the expression of either Csk or Cas Delta SD. These results demonstrate that the SFKs/Csk circuit plays crucial roles in corneal development by controlling stromal organization and by ensuring cell motility via the Cas-Rac/Cdc42 pathways.
- Published
- 2008
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38. Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury.
- Author
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Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, Kawahara N, Kuida K, Nagata S, Kominami E, Tanaka K, and Uchiyama Y
- Subjects
- Age Factors, Animals, Autophagy-Related Protein 7, Blotting, Western, Caspase 3 metabolism, Caspase 7 metabolism, DNA Fragmentation, Immunohistochemistry, In Situ Nick-End Labeling, Mice, Mice, Mutant Strains, Microtubule-Associated Proteins genetics, Autophagy physiology, Hypoxia-Ischemia, Brain pathology, Hypoxia-Ischemia, Brain physiopathology, Pyramidal Cells pathology
- Abstract
Neonatal hypoxic/ischemic (H/I) brain injury causes neurological impairment, including cognitive and motor dysfunction as well as seizures. However, the molecular mechanisms regulating neuron death after H/I injury are poorly defined and remain controversial. Here we show that Atg7, a gene essential for autophagy induction, is a critical mediator of H/I-induced neuron death. Neonatal mice subjected to H/I injury show dramatically increased autophagosome formation and extensive hippocampal neuron death that is regulated by both caspase-3-dependent and -independent execution. Mice deficient in Atg7 show nearly complete protection from both H/I-induced caspase-3 activation and neuron death indicating that Atg7 is critically positioned upstream of multiple neuronal death executioner pathways. Adult H/I brain injury also produces a significant increase in autophagy, but unlike neonatal H/I, neuron death is almost exclusively caspase-3-independent. These data suggest that autophagy plays an essential role in triggering neuronal death execution after H/I injury and Atg7 represents an attractive therapeutic target for minimizing the neurological deficits associated with H/I brain injury.
- Published
- 2008
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- View/download PDF
39. Dynamic change of histone H2AX phosphorylation independent of ATM and DNA-PK in mouse skin in situ.
- Author
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Koike M, Mashino M, Sugasawa J, and Koike A
- Subjects
- Animals, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins genetics, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Immunohistochemistry, Mice, Mice, Knockout, Phosphorylation, Protein Serine-Threonine Kinases deficiency, Protein Serine-Threonine Kinases genetics, Skin radiation effects, Tumor Suppressor Proteins deficiency, Tumor Suppressor Proteins genetics, Cell Cycle Proteins metabolism, DNA metabolism, DNA-Activated Protein Kinase metabolism, DNA-Binding Proteins metabolism, Histones metabolism, Nuclear Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Skin metabolism, Tumor Suppressor Proteins metabolism
- Abstract
Histone H2AX undergoes phosphorylation on Ser 139 (gamma-H2AX) rapidly in response to DNA double-strand breaks induced by exogenous stimuli, such as ionizing radiation. However, the endogenous phosphorylation pattern and modifier of H2AX remain unclear. Here we show that H2AX is regulated physically at the level of phosphorylation at Ser139 during a hair cycle in the mouse skin. In anagen hair follicles, gamma-H2AX-positive cells were observed in the outer root sheath (ORS) and hair bulb in a cycling inferior region but not in a permanent superficial region. In telogen hair follicles, gamma-H2AX-positive cells were only detected around the germ cell cap. In contrast, following X-irradiation, gamma-H2AX was observed in various cell types including the ORS cells in the permanent superficial region. Furthermore, gamma-H2AX-positive cells were detected in the skin of mice lacking either ATM or DNA-PK, suggesting that these kinases are not essential for phosphorylation in vivo.
- Published
- 2007
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40. Modeling wear of cast Ti alloys.
- Author
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Chan KS, Koike M, and Okabe T
- Subjects
- Dental Alloys chemistry, Elasticity, Hardness, Hardness Tests, Materials Testing, Microscopy, Electron, Scanning, Stress, Mechanical, Structure-Activity Relationship, Tensile Strength, Alloys chemistry, Titanium chemistry
- Abstract
The wear behavior of Ti-based alloys was analyzed by considering the elastic-plastic fracture of individual alloys in response to the relevant contact stress field. Using the contact stresses as the process driving force, wear was computed as the wear rate or volume loss as a function of hardness and tensile ductility for Ti-based cast alloys containing an alpha, alpha+beta or beta microstructure with or without the intermetallic precipitates. Model predictions indicated that wear of Ti alloys increases with increasing hardness but with decreasing fracture toughness or tensile ductility. The theoretical results are compared with experimental data to elucidate the roles of microstructure in wear and contrasted against those in grindability.
- Published
- 2007
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- View/download PDF
41. Endotoxin-induced injury of the central, autonomic and enteric nervous systems and intestinal muscularis in Thoroughbred horses.
- Author
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Oikawa M, Ohnami Y, Koike M, Park CH, and Oyamada T
- Subjects
- Animals, Brain drug effects, Brain pathology, Disease Models, Animal, Edema chemically induced, Edema pathology, Endotoxemia pathology, Horse Diseases pathology, Horses, Intestines drug effects, Intestines pathology, Muscle, Smooth drug effects, Muscle, Smooth pathology, Myenteric Plexus drug effects, Myenteric Plexus ultrastructure, Necrosis chemically induced, Necrosis pathology, Nervous System pathology, Nervous System Diseases pathology, Peripheral Nerves drug effects, Peripheral Nerves ultrastructure, Endotoxemia chemically induced, Escherichia coli chemistry, Horse Diseases chemically induced, Lipopolysaccharides toxicity, Nervous System drug effects, Nervous System Diseases chemically induced
- Abstract
To evaluate the effects of endotoxin on the morphology of the equine central, autonomic and enteric nervous system and intestinal muscularis, six Thoroughbred horses with experimentally induced endotoxaemia were examined. The lesions in the central nervous system consisted of perivascular oedema around arterioles, suggesting brain oedema, and ring haemorrhages around veins, similar to those in human patients with septic shock. In the cranial mesenteric ganglia, neuronal cell bodies became pink or red, with shrinkage of cytoplasm indicative of ischaemic changes; intramural and perivascular infiltration by erythrocytes and neutrophils occurred around arterioles in the epineurium (acute focal interstitial inflammation). In addition, transmission electron microscopy revealed oedema of the endoneurium and mesoaxon in the nerve fascicles running inside or outside the ganglia. Myenteric neurons showed shrinkage of the cytoplasm with multiple cytoplasmic vacuoles, suggesting ischaemic changes. Oedematous degeneration and coagulation necrosis of smooth muscle cells, with dissociation of the cells, were prominent in the tunica muscularis. It is suggested that arterionecrosis elicited by endotoxin and frequently observed in the autonomic and enteric nervous system and intestinal muscularis, was the result of vasoconstriction or vasospasm.
- Published
- 2007
- Full Text
- View/download PDF
42. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease).
- Author
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Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, Kominami E, Gotow T, Peters C, von Figura K, Mizushima N, Saftig P, and Uchiyama Y
- Subjects
- Animals, Autophagy, Cathepsin B deficiency, Cathepsin B genetics, Cathepsin D deficiency, Cathepsin D genetics, Disease Models, Animal, Freeze Fracturing, Genetic Carrier Screening, Mice, Mice, Knockout, Neuronal Ceroid-Lipofuscinoses genetics, Neurons ultrastructure, Reverse Transcriptase Polymerase Chain Reaction, Lysosomes pathology, Neuronal Ceroid-Lipofuscinoses pathology, Neurons pathology
- Abstract
In cathepsin D-deficient (CD-/-) and cathepsins B and L double-deficient (CB-/-CL-/-) mice, abnormal vacuolar structures accumulate in neurons of the brains. Many of these structures resemble autophagosomes in which part of the cytoplasm is retained but their precise nature and biogenesis remain unknown. We show here how autophagy contributes to the accumulation of these vacuolar structures in neurons deficient in cathepsin D or both cathepsins B and L by demonstrating an increased conversion of the molecular form of MAP1-LC3 for autophagosome formation from the cytosolic form (LC3-I) to the membrane-bound form (LC3-II). In both CD-/- and CB-/-CL-/- mouse brains, the membrane-bound LC3-II form predominated whereas MAP1-LC3 signals accumulated in granular structures located in neuronal perikarya and axons of these mutant brains and were localized to the membranes of autophagosomes, evidenced by immunofluorescence microscopy and freeze-fracture-replica immunoelectron microscopy. Moreover, as in CD-/- neurons, autofluorescence and subunit c of mitochondrial ATP synthase accumulated in CB-/-CL-/- neurons. This suggests that not only CD-/- but also CB-/-CL-/- mice could be useful animal models for neuronal ceroid-lipofuscinosis/Batten disease. These data strongly argue for a major involvement of autophagy in the pathogenesis of Batten disease/lysosomal storage disorders.
- Published
- 2005
- Full Text
- View/download PDF
43. Oral bacteria in the occluded arteries of patients with Buerger disease.
- Author
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Iwai T, Inoue Y, Umeda M, Huang Y, Kurihara N, Koike M, and Ishikawa I
- Subjects
- Adult, Aged, Bacterial Infections epidemiology, Chronic Disease, Comorbidity, DNA, Bacterial isolation & purification, Humans, Male, Middle Aged, Thromboangiitis Obliterans epidemiology, Arteries microbiology, Dental Plaque microbiology, Saliva microbiology, Thromboangiitis Obliterans microbiology
- Abstract
Objective: Recent studies have suggested that infectious organisms play a role in vascular diseases. In this study, to explore a possible link between oral infection and Buerger disease, we investigated whether oral (periodontal) bacteria were present in occluded arteries removed from patients with characteristic Buerger disease., Methods: Fourteen male patients with a smoking history who had developed characteristics of Buerger disease before the age of 50 years were included in this study. Occluded arteries, including superficial femoral (n = 4), popliteal (n = 2), anterior tibial (n = 4), and posterior tibial (n = 4) arteries, were removed and studied. A periodontist performed a periodontal examination on each patient and collected dental plaque and saliva samples from them at the same time. The polymerase chain reaction method was applied to detect whether seven species of periodontal bacteria--Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella intermedia , and Prevotella nigrescens--were present in the occluded arteries and oral samples. In addition, arterial specimens from seven control patients were examined by polymerase chain reaction analysis., Results: DNA of oral bacteria was detected in 13 of 14 arterial samples and all oral samples of patients with Buerger disease. Treponema denticola was found in 12 arterial and all oral samples. Campylobacter rectus, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, and Prevotella nigrescens were found in 14% to 43% of the arterial samples and 71% to 100% of the oral samples. A pathologic examination revealed that arterial specimens showed the characteristics of an intermediate-chronic-stage or chronic-stage lesion of Buerger disease. All 14 patients with Buerger disease had moderate to severe periodontitis. None of the control arterial samples was positive for periodontal bacteria., Conclusions: This is the first study to identify oral microorganisms in the lesions of Buerger disease. Our findings suggest a possible etiologic link between Buerger disease and chronic infections such as oral bacterial infections.
- Published
- 2005
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44. Electrochemical characterization of cast Ti-Hf binary alloys.
- Author
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Cai Z, Koike M, Sato H, Brezner M, Guo Q, Komatsu M, Okuno O, and Okabe T
- Subjects
- Electrochemistry, Alloys, Hafnium chemistry, Titanium chemistry
- Abstract
This study characterized the electrochemical behavior of Ti-Hf binary alloys in a simulated oral environment. Ti-Hf alloys (10, 20, 25, 30, 35 and 40 mass% Hf) were prepared by arc-melting titanium sponge and hafnium sponge. Specimens of each alloy (n = 4) were prepared using a dental titanium casting system with a MgO-based investment. Specimens were inspected with X-ray radiography to ensure minimal internal porosity. Castings (n = 4) made from pure titanium and commercially pure titanium were used as controls. The ground flat surface (10 mm x 10 mm) on each specimen where approximately 30 microm was removed was used for the characterization. Sixteen-hour open-circuit potential (OCP) measurement, linear polarization and potentiodynamic cathodic polarization were performed sequentially in aerated (air + 10% CO2) MTZ synthetic saliva at 37 degrees C. Potentiodynamic anodic polarization was conducted in the same medium but deaerated (N2 + 10% CO2) 2 h before and during testing. Polarization resistance (R(P)) and Tafel slopes were determined, as were corrosion current density (I(CORR)) and passive current density (I(PASS)). Results were subjected to nonparametric statistical analysis (alpha = 0.05). The OCP stabilized (mean values -229 mV to -470 mV vs. SCE) for all specimens after the 16-h immersion. Similar passivation was observed for all the metals on their anodic polarization diagrams. The Kruskal-Wallis test showed significant differences in OCP among the test groups (p = 0.006). No significant differences were found in R(P), I(CORR) or I(PASS) among all the metals (p>0.3). Results indicate that the electrochemical behavior of the Ti-Hf alloys examined resembles that of pure titanium.
- Published
- 2005
- Full Text
- View/download PDF
45. Treatment of three pancreaticoduodenal artery aneurysms associated with coeliac artery occlusion and splenic artery aneurysm: a case report and review of the literature.
- Author
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Jibiki M, Inoue Y, Iwai T, Sugano N, Igari T, and Koike M
- Subjects
- Aneurysm diagnosis, Arterial Occlusive Diseases diagnosis, Blood Vessel Prosthesis, Female, Humans, Middle Aged, Splenectomy, Aneurysm surgery, Arterial Occlusive Diseases surgery, Celiac Artery surgery, Duodenum blood supply, Pancreas blood supply, Splenic Artery surgery
- Abstract
A case of three pancreaticoduodenal artery (PDA) aneurysms associated with coeliac artery occlusion and a concomitant splenic arterial aneurysm is described. Surgical treatment was used because it was anticipated that the hepatic blood supply would be obstructed completely if percutaneous transluminal embolization for three PDA aneurysms were performed. Splenectomy in continuity with the splenic artery aneurysm and PDA aneurysmectomies were performed, and infrarenal abdominal aorto-splenic artery bypass was accomplished using a 6mm ringed expanded polytetrafluoroethylene graft. The postoperative course was uneventful. Graft patency and successful aneurysm ablation were confirmed using MRA and intravenous DSA. Arterial histology revealed segmental arterial mediolysis. At 2-year follow-up, the patient was well and asymptomatic. A literature review of PDA aneurysms is presented.
- Published
- 2005
- Full Text
- View/download PDF
46. Coexposure to benzo[a]pyrene plus UVA induced DNA double strand breaks: visualization of Ku assembly in the nucleus having DNA lesions.
- Author
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Toyooka T, Ibuki Y, Koike M, Ohashi N, Takahashi S, and Goto R
- Subjects
- Animals, CHO Cells, Carrier Proteins genetics, Cell Nucleus drug effects, Cell Nucleus metabolism, Cell Nucleus radiation effects, Cricetinae, Electrophoresis, Agar Gel, Ku Autoantigen, Microscopy, Confocal, Mutation, Time Factors, Benzo(a)pyrene pharmacology, Carrier Proteins biosynthesis, DNA drug effects, DNA radiation effects, DNA Helicases, Mutagens pharmacology, Ultraviolet Rays
- Abstract
Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant with potential carcinogenicity. It has been shown that BaP, upon UVA irradiation, synergistically induced oxidative DNA damage, but other DNA damage was not confirmed. In this study, we examined whether coexposure to BaP plus UVA induces double strand breaks (DSBs) using xrs-5 cells, deficient in the repair of DSBs (Ku80 mutant), and whether Ku translocates involving the formation of DSBs. BaP plus UVA had a significant cytotoxic effect on CHO-K1 cells and an even more drastic effect on Ku80-deficient, xrs-5 cells, suggesting that the DSBs were generated by coexposure to BaP plus UVA. The DSBs were repaired in CHO-K1 cells within 30 min, but not in xrs-5 cells, indicating the involvement of a non-homologous end joining, which needs Ku proteins. Furthermore, we succeeded in visualizing that Ku80 rapidly assembled to the exposed region, in which DSBs might be generated, and clarified that the presence of both Ku70 and Ku80 was important for their accumulation.
- Published
- 2004
- Full Text
- View/download PDF
47. Expression of IAP family proteins in esophageal cancer.
- Author
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Nemoto T, Kitagawa M, Hasegawa M, Ikeda S, Akashi T, Takizawa T, Hirokawa K, and Koike M
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Squamous Cell diagnosis, Esophageal Neoplasms diagnosis, Female, Humans, Immunoenzyme Techniques, In Situ Hybridization, Inhibitor of Apoptosis Proteins, Male, Microtubule-Associated Proteins genetics, Microtubule-Associated Proteins metabolism, Middle Aged, Neoplasm Proteins, Neuronal Apoptosis-Inhibitory Protein, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Survivin, Ubiquitin-Protein Ligases, X-Linked Inhibitor of Apoptosis Protein, Apoptosis, Carcinoma, Squamous Cell genetics, Esophageal Neoplasms genetics, Nerve Tissue Proteins genetics, Proteins genetics
- Abstract
Members of the inhibitor of apoptosis protein (IAP) family, including survivin, have been reported to be expressed in many tumors. However, their expression in esophageal cancer has not been clarified completely. We investigated the expression of mRNA for IAP family proteins in samples from esophageal cancers and their adjacent normal mucosa tissues by real-time quantitative RT-PCR. The survivin expression in esophageal cancer was significantly higher than that in normal mucosa (P < 0.05). Other IAP family proteins including cIAP1, cIAP2, NAIP and XIAP tended to show stronger expression in cancer tissue than normal mucosa, although the differences were not significant. As to the histological type of tumor, poorly differentiated squamous cell carcinomas exhibited significantly higher level of expression than well-differentiated carcinomas (P < 0.05). The proportion of apoptotic cells of cancer tissue inversely correlated with the intensity of survivin expression (P < 0.05). Immunohistochemical staining demonstrated cytoplasmic as well as nuclear expression of survivin in esophageal cancer, and further, in situ hybridization analysis demonstrated cytoplasmic expression of mRNA for survivin. The results suggest that the expression of IAP family proteins, especially survivin, may be associated with the biological character of esophageal cancer, such as apoptosis.
- Published
- 2004
- Full Text
- View/download PDF
48. Study on the practical use of quantitative whole-body auto-radioluminography.
- Author
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Inazawa K, Koike M, and Yamaguchi T
- Subjects
- Animals, Calibration, Male, Rats, Reference Standards, Reproducibility of Results, Sensitivity and Specificity, Autoradiography instrumentation, Autoradiography methods, Whole-Body Counting instrumentation, Whole-Body Counting methods
- Abstract
The practical use of quantitative radioluminography (RLG) using reading system BAS 2000 (Fuji Photo Film Ltd., Tokyo, Japan) and STORM 820 (Molecular Dynamics, USA) was examined using a chemical matrix as an internal standard, which offers the benefits of being preservative, inexpensive, and easy to handle. The results were as follows: 1. As the water content is within the range of 65-80% for most organs and tissues, we selected a chemical matrix, Tissue-TEK containing 85% water, as a base for the preparation of a standard curve. 2. The calibration curve prepared using Tissue-Tek as the internal standard was compared with the calibration curve using liver paste preparations as the internal standard. The results showed good linearity in both cases, with almost no difference in the slopes of the two calibration curves. 3. The PSL-BG or MD counts/pixel-BG values of the lowest radioactivity concentration measured for small areas of the region of interest (ROI) showed large fluctuations with both BAS 2000 and STORM 820, but the fluctuation became less than 15% at above 25 mm(2) of ROI. 4. The value of dpm/g calculated using the calibration curve prepared from Tissue-Tex internal standards showed a very good correlation with the values of dpm/g obtained by scraping off the tissue from the remaining block and conducting measurements with a liquid scintillation counter.
- Published
- 2004
- Full Text
- View/download PDF
49. In vivo recognition of cyclopentadienyltricarbonylrhenium (CpTR) derivatives.
- Author
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Uehara T, Koike M, Nakata H, Miyamoto S, Motoishi S, Hashimoto K, Oku N, Nakayama M, and Arano Y
- Subjects
- Animals, Chromatography, High Pressure Liquid, Male, Mice, Organometallic Compounds chemical synthesis, Organometallic Compounds pharmacokinetics, Tissue Distribution, Organometallic Compounds metabolism
- Abstract
In vivo metabolism of [(188)Re]tricarbonyl(carboxycyclopentadienyl)rhenium ([(188)Re]CpTR-COOH) and its glycine conjugate ([(188)Re]CpTR-Gly) was investigated to estimate the applicability of cyclopentadienyltricarbonylrhenium (CpTR) compounds to (186/188)Re-labeling reagents for polypeptides and peptides. Both [(188)Re]CpTR derivatives were stable after incubation in a buffered-solution and in murine plasma at 37 degrees C for 6 h. Plasma protein binding was hardly observed with the two derivatives. However, different biodistribution and metabolic fates were observed with the two CpTR derivatives. While more lipophilic [(188)Re]CpTR-COOH was excreted by both hepatobiliary and urinary excretion, the majority of less lipophilic [(188)Re]CpTR-Gly was excreted by urinary excretion. In addition, while [(188)Re]CpTR-Gly was rapidly excreted into urine as its intact structure, [(188)Re]CpTR-COOH was metabolized to more hydrophilic compounds including its glycine conjugate, [(188)Re]CpTR-Gly. Renal excretion of [(188)Re]CpTR-Gly was significantly reduced in probenecid retreated mice. The present studies reinforced that CpTR core remained stable under biological environment. CpTR-COOH was partially recognized as an aromatic acid and was metabolized as such. However, glycine conjugation rendered CpTR-COOH hydrophilic enough to be excreted into urine without further metabolism. These findings suggested that radiolabeling reagents that liberate [(186/188)Re]CpTR-Gly from covalently conjugated (186/188)Re-labeled polypeptides and peptides by the action of renal brush border enzymes would be useful to reduce renal radioactivity levels.
- Published
- 2003
- Full Text
- View/download PDF
50. A novel plant defensin-like gene of winter wheat is specifically induced during cold acclimation.
- Author
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Koike M, Okamoto T, Tsuda S, and Imai R
- Subjects
- Amino Acid Sequence, Anti-Bacterial Agents pharmacology, Antifreeze Proteins pharmacology, Base Sequence, DNA, Complementary isolation & purification, Molecular Sequence Data, Phylogeny, Plant Proteins biosynthesis, Plant Proteins pharmacology, RNA, Plant biosynthesis, Sequence Homology, Amino Acid, Triticum genetics, Triticum metabolism, Up-Regulation, Acclimatization, Cold Temperature, Defensins, Genes, Plant, Plant Proteins genetics, Triticum physiology
- Abstract
A novel cDNA clone, Tad1, was isolated from crown tissue of winter wheat after differential screening of cold acclimation-induced genes. The Tad1 cDNA encoded a 23kDa polypeptide with a potential N-terminal signal sequence. The putative mature sequence showed striking similarity to plant defensins or gamma-thionins, representing low molecular size antipathogenic polypeptides. High levels of Tad1 mRNA accumulation occurred within one day of cold acclimation in crown tissue and the level was maintained throughout 14 days of cold acclimation. Similar rapid induction was observed in young seedlings treated with low temperature but not with exogenous abscisic acid. In contrast to defensins from other plant species, neither salicylic acid nor methyl jasmonate induced expression of Tad1. The recombinant mature form of TAD1 polypeptide inhibited the growth of the phytopathogenic bacteria, Pseudomonas cichorii; however, no antifreeze activity was detected. Collectively, these data suggested that Tad1 is induced in cold-acclimated winter wheat independent of major defense signaling(s) and is involved in low temperature-induced resistance to pathogens during winter hardening.
- Published
- 2002
- Full Text
- View/download PDF
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