2022/11/26 更新

写真a

タカハシ ジュンコ
高橋 淳子
Scopus 論文情報  
論文数: 0  Citation: 0  h-index: 9

Citation Countは当該年に発表した論文の被引用数

所属
理工学術院 大学院情報生産システム研究科
職名
教授(任期付)

学内研究所・附属機関兼任歴

  • 2021年
    -
    2022年

    理工学術院総合研究所   兼任研究員

学位

  • 東北大学   博士(工学)

経歴

  • 2021年04月
    -
    継続中

    早稲田大学   大学院情報生産システム研究科   教授

  • 2003年04月
    -
    2021年03月

    国立研究開発法人産業技術総合研究所   バイオメディカル研究部門   主任研究員

 

研究分野

  • 生体医工学

研究キーワード

  • 放射線力学療法

  • 5-アミノレブリン酸

  • 放射線治療

  • 放射線増感剤

  • 遺伝子発現解析

論文

  • In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy.

    Junko Takahashi, Shinsuke Nagasawa, Motomichi Doi, Masamichi Takahashi, Yoshitaka Narita, Junkoh Yamamoto, Mitsushi J Ikemoto, Hitoshi Iwahashi

    International journal of molecular sciences   22 ( 18 )  2021年09月  [国際誌]

     概要を見る

    To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

    DOI PubMed

    Scopus

    2
    被引用数
    (Scopus)
  • Detection and monitoring of insect traces in bioaerosols

    Panyapon Pumkaeo, Junko Takahashi, Hitoshi Iwahashi

    PeerJ   9  2021年02月

     概要を見る

    Studies on bioaerosols have primarily focused on their chemical and biological compositions and their impact on public health and the ecosystem. However, most bioaerosol studies have only focused on viruses, bacteria, fungi, and pollen. To assess the diversity and composition of airborne insect material in particulate matter (PM) for the first time, we attempted to detect DNA traces of insect origin in dust samples collected over a two-year period. These samples were systematically collected at one-month intervals and categorized into two groups, PM2.5 and PM10, based on the aerodynamic diameter of the aerosol particles. Cytochrome-c oxidase I (COI) was the barcoding region used to identify the origins of the extracted DNA. The airborne insect community in these samples was analyzed using the Illumina MiSeq platform. The most abundant insect sequences belonged to the order Hemiptera (true bugs), whereas order Diptera were also detected in both PM2.5 and PM10 samples. Additionally, we inferred the presence of particulates of insect origin, such as brochosomes and integument particles, using scanning electron microscopy (SEM). This provided additional confirmation of the molecular results. In this study, we demonstrated the benefits of detection and monitoring of insect information in bioaerosols for understanding the source and composition. Our results suggest that the PM2.5 and PM10 groups are rich in insect diversity. Lastly, the development of databases can improve the identification accuracy of the analytical results.

    DOI

    Scopus

    1
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  • Detection and monitoring of insect traces in bioaerosols.

    Panyapon Pumkaeo, Junko Takahashi, Hitoshi Iwahashi

    PeerJ   9   e10862  2021年  [国際誌]

     概要を見る

    Studies on bioaerosols have primarily focused on their chemical and biological compositions and their impact on public health and the ecosystem. However, most bioaerosol studies have only focused on viruses, bacteria, fungi, and pollen. To assess the diversity and composition of airborne insect material in particulate matter (PM) for the first time, we attempted to detect DNA traces of insect origin in dust samples collected over a two-year period. These samples were systematically collected at one-month intervals and categorized into two groups, PM2.5 and PM10, based on the aerodynamic diameter of the aerosol particles. Cytochrome-c oxidase I (COI) was the barcoding region used to identify the origins of the extracted DNA. The airborne insect community in these samples was analyzed using the Illumina MiSeq platform. The most abundant insect sequences belonged to the order Hemiptera (true bugs), whereas order Diptera were also detected in both PM2.5 and PM10 samples. Additionally, we inferred the presence of particulates of insect origin, such as brochosomes and integument particles, using scanning electron microscopy (SEM). This provided additional confirmation of the molecular results. In this study, we demonstrated the benefits of detection and monitoring of insect information in bioaerosols for understanding the source and composition. Our results suggest that the PM2.5 and PM10 groups are rich in insect diversity. Lastly, the development of databases can improve the identification accuracy of the analytical results.

    DOI PubMed

    Scopus

    1
    被引用数
    (Scopus)
  • Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review.

    Junko Takahashi, Shinsuke Nagasawa

    International journal of molecular sciences   21 ( 23 )  2020年12月  [国際誌]

     概要を見る

    Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large.

    DOI PubMed

    Scopus

    9
    被引用数
    (Scopus)
  • DNA Strand Break Properties of Protoporphyrin IX by X-Ray Irradiation against Melanoma.

    Takema Hasegawa, Junko Takahashi, Shinsuke Nagasawa, Motomichi Doi, Akihiro Moriyama, Hitoshi Iwahashi

    International journal of molecular sciences   21 ( 7 )  2020年03月  [査読有り]  [国際誌]

     概要を見る

    Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3'-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2•-). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2•- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

    DOI PubMed

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    4
    被引用数
    (Scopus)
  • Screening of X-ray responsive substances for the next generation of radiosensitizers.

    Akihiro Moriyama, Takema Hasegawa, Lei Jiang, Hitoshi Iwahashi, Takashi Mori, Junko Takahashi

    Scientific reports   9 ( 1 ) 18163 - 18163  2019年12月  [査読有り]  [国際誌]

     概要を見る

    X-ray responsivity resulting in the generation of reactive oxygen species (ROS) was investigated in 9600 organic compounds that were selected by considering their structural diversity. We focused on superoxides that were primarily detected using dihydroethidium (DHE) and hydroxyl radicals, that were identified fluorometrically using 3'-(p-aminophenyl) Fluorescein (APF). Many organic compounds were discovered that responded to the DHE and/or APF assay using X-ray irradiation. These results suggest that some of these organic compounds emit either superoxides or hydroxyl radicals whereas others emit both under the influence of X-ray irradiation. The response of the derivatives of a hit compound with a partial change in the structure was also investigated. The products produced from DHE by X-ray irradiation were identified by HPLC to confirm the integrity of the process. Although, the reactions were suppressed by the superoxide dismutase (SOD), not only 2-hydroxyethidium (2-OH-E+), but also ethidium (E+) were detected. The results suggest that apart from a direct reaction, an indirect reaction may occur between DHE and the superoxides. Although X-ray responsiveness could not be inferred due to the molecular complexity of the investigated compounds, delineation of these reactions will facilitate the development of the next generation of radiosensitizers.

    DOI PubMed

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    2
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  • Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model.

    Junko Takahashi, Shinsuke Nagasawa, Mitsushi J Ikemoto, Chikara Sato, Mari Sato, Hitoshi Iwahashi

    International journal of molecular sciences   20 ( 20 )  2019年10月  [査読有り]  [国際誌]

     概要を見る

    Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, ("radiodynamic therapy (RDT)"), instead of with 5-ALA and laser beams ("photodynamic therapy"), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ∙OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy.

    DOI PubMed

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    11
    被引用数
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  • Assessment of harmfulness and biological effect of carbon fiber dust generated during new carbon fiber recycling method.

    Akihiro Moriyama, Takema Hasegawa, Chisato Nagaya, Kazuhiro Hamada, Takehiro Himaki, Mami Murakami, Masanori Horie, Junko Takahashi, Hitoshi Iwahashi, Hiroshi Moritomi

    Journal of hazardous materials   378   120777 - 120777  2019年10月  [査読有り]  [国際誌]

     概要を見る

    Concern over the effects of nanomaterials on human health has risen due to the dramatic advances in the development of various technologies based on nanomaterials. Gifu Prefecture and Gifu University are developing technologies for recycling used carbon fiber because the waste disposal process is highly cost and energy intensive. However, generation of carbon fiber dust during the recycling process is a serious issue, especially in the occupational environment. Recycling requires carbonization by partial firing treatment at 500℃ followed by firing treatment at 440℃: these processes produce dust as a by-product. It is important to study the influence of carbon fibers on human health at a molecular level. In this study, three types of carbon fibers - before recycling, after carbonization, and after firing were evaluated for their toxic effects on mice. During the breeding period, no loss in body weight was confirmed. Further, by staining the lung tissue sections, it was found that pulmonary fibrosis did not occur. We found that these carbon fibers might not possess severe toxicity. However, we also found that the toxicity varies according to firing treatment. Furthermore, we found that firing treatment reduces the potential hazard to human health.

    DOI PubMed

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    13
    被引用数
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  • The Truth of Toxicity Caused by Yttrium Oxide Nanoparticles to Yeast Cells.

    Akihiro Moriyama, Ukyo Takahashi, Youta Mizuno, Junko Takahashi, Masanori Horie, Hitoshi Iwahashi

    Journal of nanoscience and nanotechnology   19 ( 9 ) 5418 - 5425  2019年09月  [査読有り]  [国際誌]

     概要を見る

    Yttrium oxide (Y₂O₃) nanoparticles have widespread applications; however, toxicity due to these nanoparticles has also been reported. In this study, we evaluated the in vitro toxicity of Y₂O₃ nanoparticles according to the technical specifications published by the International Standard Organization (ISO/TS 19337:2016). We used Saccharomyces cerevisiae as a model microorganism represented the environment. We carried out catch ball analysis of yttrium oxide and yttrium ion toxicities. The result showed that Y₂O₃ nanoparticles (20 mg/5 ml) and YCl₃ (5 mg/5 ml) treatment caused oxidative stress in yeast cells. Based on transcriptome analysis, fluorescent spectroscopy, and solubility analysis of Y₂O₃ nanoparticles, we conclude that the toxicity is due to yttrium ions derived from the nanoparticles. The ions induce oxidative stress and cause protein denaturation, which in turn induces proteasome formation to eliminate denatured proteins. Yttrium nanoparticles induce oxidative stress, which has associated with heavy metal ions. Thus, the use of yttrium nanoparticles or yttrium ions must be controlled like heavy metals.

    DOI PubMed

  • Relationship between Flavonoid Structure and Reactive Oxygen Species Generation upon Ultraviolet and X-ray Irradiation

    Jiang, L, Yanase, E, Mori, T, Kurata, K, Toyama, T, Tsuchiya, A, Yamauchi, K, Mitsunaga, T, Iwahashi, H, Takahashi, J

    Journal of Photochemistry & Photobiology A: Chemistry   384   112044  2019年  [査読有り]

    DOI

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    3
    被引用数
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  • The Truth of Toxicity Caused by Yttrium Oxide Nanoparticles to Yeast Cells.

    Moriyama, A, Takahashi, U, Mizuno,Y, Takahashi, J, Horie, M, Iwahashi, H

    Journal of Nanoscience and Nanotechnology   294   144 - 150  2019年  [査読有り]

  • Evaluation of the effect of high pressure carbon dioxide-pasteurized food on animal health.

    Hibi A, Ohno, T, Moriyama, A, Himaki, T, Takahashi, J, Iwahashi, H

    High Pressure Research   39 ( 2 ) 357 - 366  2019年  [査読有り]

  • Oxidative stress caused by TiO2 nanoparticles under UV irradiation is due to UV irradiation not through nanoparticles.

    Akihiro Moriyama, Ikuho Yamada, Junko Takahashi, Hitoshi Iwahashi

    Chemico-biological interactions   294   144 - 150  2018年10月  [査読有り]  [国際誌]

     概要を見る

    Currently, nanoparticles are used in various commercial products. One of the most common nanoparticles is titanium dioxide (TiO2). It has a catalytic activity and UV absorption, and generates reactive oxygen species (ROS). This catalytic activity of TiO2 nanoparticles was believed to be capable of killing a wide range of microorganisms. In the environment, the unique properties of TiO2 nanoparticles can be maintained; therefore, the increasing use of TiO2 nanoparticles is raising concerns about their environmental risks. Thus, assessment of the biological and ecological effects of TiO2-NOAAs is necessary. In this study, we assessed the effect of TiO2-NOAAs for S. cerevisiae using DNA microarray. To compare yeast cells under various conditions, six treatment conditions were prepared (1. adsorbed fraction to TiO2-NOAA under UV; 2. non-adsorbed fraction to TiO2-NOAA under UV; 3. adsorbed fraction to TiO2-NOAA without UV; 4. non-adsorbed fraction to TiO2-NOAA without UV; 5. under UV; and 6. untreated control). The result of the DNA microarray analysis, suggested that yeast cells that are adsorbed by TiO2-NOAA under UV irradiation suffer oxidative stress and this stress response was similar to that by only UV irradiation. We concluded that the effect of TiO2-NOAAs on yeast cells under UV irradiation is not caused by TiO2-NOAA but UV irradiation.

    DOI PubMed

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    9
    被引用数
    (Scopus)
  • Self-assembled nanodiamond supraparticles for anticancer chemotherapy

    Yue Yu, Masahiro Nishikawa, Ming Liu, Takahiro Tei, Sunil C. Kaul, Renu Wadhawa, Minfang Zhang, Junko Takahashi, Eijiro Miyako

    Nanoscale   10 ( 19 ) 8969 - 8978  2018年05月  [査読有り]

     概要を見る

    A nanodiamond (ND) is a promising material for drug delivery applications owing to its relatively low cost, amenability to large-scale synthesis, unique structure, and low toxicity. However, synthesizing drug-loaded ND conjugates with uniform and tunable sizes, high loading capacity, efficacy in drug delivery, and versatility in terms of surface functionalization has been challenging. Here, we show that perfluorooctanoic acid-functionalized NDs spontaneously transform into well-dispersed and biocompatible supraparticle (SP) nanoclusters. We demonstrate that the synthesized ND-based SPs (ND-SPs) exhibit high penetration through the cell membrane and are therefore superior as drug carriers for conventional nanomedicines such as polyethylene glycol and phospholipid-based nanocapsules and simple drug-loaded ND conjugates. We confirm the efficacy of ND-SPs in the eradication of cancer cells in vitro and in vivo. Our results demonstrate that the synthesized ND-SPs are useful for targeted drug delivery in a variety of biological applications.

    DOI PubMed

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    20
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  • Luteolin as reactive oxygen generator by X-ray and UV irradiation

    Michiru Toyama, Takashi Mori, Junko Takahashi, Hitoshi Iwahashi

    RADIATION PHYSICS AND CHEMISTRY   146   11 - 18  2018年05月

     概要を見る

    Non-toxic X-ray-responsive substances can be used in the radiosensitization of cancer, like porphyrin mediated radiotherapy. However, most X-ray-responsive substances are toxic. To find novel non-toxic X-ray-responsive substances, we studied the X-ray and UV reactivity of 40 non-toxic compounds extracted from plants. Dihydroethidium was used as an indicator to detect reactive oxygen species (ROS) generated by the compounds under X-ray or UV irradiation. We found that 13 of the investigated compounds generated ROS under X-ray irradiation and 17 generated ROS under UV irradiation. Only 4 substances generated ROS under both X-ray and UV. In particular, luteolin exhibited the highest activity among the investigated compounds; therefore, the ROS generated by luteolin were thoroughly characterized. To identify the ROS, we employed a combination of ROS detection reagents and their quenchers. O-2 generation by luteolin was monitored using dihydroethidium and superoxide dismutase (as an O-2(-) quencher). OH and O-1(2) generation was determined using aminophenyl fluorescein with ethanol (OH quencher) and Singlet Oxygen Sensor Green with NaN3 (O-1(2) quencher), respectively. Generation of O-2(-) under X-ray and UV irradiation was observed; however, no OH or O-1(2) was detected. The production of ROS from luteolin is surprising, because luteolin is a well-known antioxidant.

    DOI

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    6
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  • Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model.

    Junko Takahashi, Mami Murakami, Takashi Mori, Hitoshi Iwahashi

    Scientific reports   8 ( 1 ) 2728 - 2728  2018年02月  [査読有り]  [国際誌]

     概要を見る

    Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

    DOI PubMed

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    27
    被引用数
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  • Oxidative stress caused by TiO2 nanoparticles under UV irradiation is due to UV irradiation not through nanoparticles.

    Moriyama, A, Yamada, I, Takahashi, J, Iwahashi H

    Chemico-Biological Interactions   19   5418 - 5425  2018年  [査読有り]

  • For Novel Disease Diagnostic Markers in Blood RNA.

    Takahashi1, J, Iwahashi, H

    Journal of Medical Diagnostic   7 ( 1 ) 1000e115  2018年01月  [査読有り]

  • RNA Quality Control Using External Standard RNA.

    Hasegawa T, Takahashi J, Iwahashi H

    Polish journal of microbiology   67 ( 3 ) 347 - 353  2018年  [査読有り]

    DOI PubMed

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    2
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  • Evaluation of the physiology of miniature pig fed Shochu distillery waste using mRNA expression profiling

    Shiori Miura, Junko Takahashi, Hitoshi Iwahashi

    Journal of Material Cycles and Waste Management   20 ( 1 ) 237 - 244  2018年01月  [査読有り]

     概要を見る

    Shochu distillery waste is the discarded material generated during Shochu production, and it has been used as feed for livestock. In this study, we evaluated the applicability of Shochu distillery waste as a livestock diet. Shochu distillery waste diet was fed to Clawn miniature pigs. At the end of the dietary period, blood samples were collected for biochemical examination and microarray analysis. No significant differences were observed between the control and Shochu distillery waste treatment groups based on physical and biochemical examination. Gene expression patterns were also similar. In addition, gene profiling of these two groups was compared with those of hyperlipidemia and toxicant model groups. Expression profiling of the two groups was different from those of the hyperlipidemia and toxicant model groups. In conclusion, the Shochu distillery waste diet did not affect pig physiology and it is a suitable substitute for standard feed. Moreover, these results promote the potential for microarray analysis use in the evaluation of food safety.

    DOI

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    2
    被引用数
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  • The role of transcriptomics: physiological equivalence based on gene expression profiles.

    Miura, S, Himaki, T, Takahashi, J, Iwahashi, H

    Reviews in Agricultural Science   5   5:21 - 525  2017年  [査読有り]

  • Introduction to 5-Aminolevulinic Acid-Protoporphyrin IX Mediated Radiodynamic Therapy (RDT)

    Takahashi, J, Iwahashi, H

    Clinics in Oncolog   2   1330  2017年  [査読有り]

  • 2.5-aminolevulinic acid - Protoporphyrin IX mediated radiodynamic therapy (RDT)

    Takahashi, J, Iwahashi, H

    ALA porphyrin Science   5   35 - 38  2016年  [査読有り]  [招待有り]

  • Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone

    Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi

    INTERNATIONAL JOURNAL OF RADIATION BIOLOGY   92 ( 12 ) 774 - 789  2016年  [査読有り]

     概要を見る

    Purpose: 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer protoporphyrin (PpIX) used in photodynamic therapy. In our previous work, PpIX enhanced the generation of reactive oxygen species by X-ray irradiation. In this study, we evaluated the potential of ALA as an endogenous sensitizer to X-ray irradiation.
    Methodology: Tumor-bearing C57BL/6J mice implanted with B16-BL6 melanoma cells were subsequently treated with irradiation (3Gy/day for 10 days; total, 30Gy) plus local administration of 50mg/kg ALA 24 hours prior to each irradiation (ALA-XT). Tumor-bearing mice without treatment (NT), those treated with ALA only (ALAT), and those treated with X-ray irradiation only (XT) were used as controls.
    Results: ALA potentiated tumor suppression by X-ray irradiation. In microarray analyses using tumor tissue collected after 10 sessions of fractional irradiation, functional analysis revealed that the majority of dysregulated genes in the XT and ALA-XT groups were related to cell-cycle arrest. Finally, the XT and ALA-XT groups differed in the strength of expression, but not in the pattern of expression.
    Conclusions: mRNA analysis revealed that the combined use of ALA and X-ray irradiation sensitized tumors to X-ray treatment. Furthermore, the present results were consistent with ALA's tumor suppressive effects in vivo.

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  • Gene expression profiling can predict the fate of HeLa cells exposed to X-ray irradiation with or without protoporphyrin accumulation.

    Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi

    Genomics data   5   192 - 4  2015年09月  [査読有り]  [国際誌]

     概要を見る

    Protoporphyrin IX (PpIX) enhances the generation of reactive oxygen species in cells following physicochemical interactions with X-rays. To evaluate the use of porphyrins as radio-sensitizers in radiotherapy, the transcriptomic effects of PpIX and/or X-ray irradiation were investigated in HeLa cells. Microarray experiments were performed using Agilent-014,850 Whole Human Genome Microarray 4x44K G4112F (GEO#: GSE61805). We selected the condition corresponding to 1 μg/mL PpIX exposure prior to 3 Gy-irradiation of cells, and collected cells 24 h post irradiation. X-ray exposure at a dose of 3 Gy did not affect cell survival 24 h post irradiation, regardless of the concentration of PpIX. Approximately 50% cells exposed to X-ray irradiation alone (XT) and 70% cells exposed to PpIX treatment for 6 h before X-ray irradiation (PpIX-XT) lost clonogenic ability. Based on p-values (p < 0.01), we selected genes for functional analysis. The majority of the regulated genes in the XT and PpIX-XT groups were related to cell cycle arrest. Furthermore, transcriptome analysis of the cells collected 24 h post irradiation revealed the fate of the cells that lost clonogenic ability due to cell cycle arrest.

    DOI PubMed

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    1
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  • Transcriptome Analysis of Porphyrin-Accumulated and X-Ray-Irradiated Cell Cultures under Limited Proliferation and Non-Lethal Conditions.

    Takahashi J, Misawa M, Iwahashi H

    Microarrays (Basel, Switzerland)   4 ( 1 ) 25 - 40  2015年01月  [査読有り]  [国際誌]

    DOI PubMed

  • 屋内外大気中スギアレルゲン量の粒径別測定および微小スギ花粉を用いたろ材性能評価

    片山 秀夫, 高橋 淳子, 岸本 敏始

    空気清浄 : コンタミネーションコントロール   52 ( 3 ) 201 - 211  2014年

    CiNii

  • 5-Aminolevulinic acid enhances cancer radiotherapy in a mouse tumor model

    Junko Takahashi, Masaki Misawa, Mami Murakami, Takashi Mori, Kazuki Nomura, Hitoshi Iwahashi

    SPRINGERPLUS   2  2013年  [査読有り]

     概要を見る

    5-Aminolevulinic acid (ALA) is a photosensitizer used in photodynamic therapy (PDT) because it causes preferential accumulation of protoporphyrin IX (PpIX) in tumor cells, where it forms singlet oxygen upon light irradiation and kills the tumor cells. Our previous study demonstrated that PpIX enhances generation of reactive oxygen species by physicochemical interaction with X-rays. We investigated the effect of ALA administration with X-ray irradiation of mouse B16-BL6 melanoma cells in vitro and in vivo. ALA facilitates PpIX accumulation in tumor cells and enhances ROS generation in vitro. Tumor suppression significantly improved in animals treated with fractionated doses of radiation (3 Gy x 10; total, 30 Gy) with local administration of 50 mg/kg ALA at 24 h prior to fractional irradiation. These results suggest ALA may improve the efficacy of cancer radiotherapy by acting as a radiomediator.

    DOI

    Scopus

    32
    被引用数
    (Scopus)
  • Oligonucleotide Microarray Analysis of Dietary-Induced Hyperlipidemia Gene Expression Profiles in Miniature Pigs

    Junko Takahashi, Shiori Waki, Rena Matsumoto, Junji Odake, Takayuki Miyaji, Junichi Tottori, Takehiro Iwanaga, Hitoshi Iwahashi

    PLOS ONE   7 ( 5 )  2012年05月  [査読有り]

     概要を見る

    Background: Hyperlipidemia animal models have been established, but complete gene expression profiles of the transition from normal lipid levels have not been obtained. Miniature pigs are useful model animals for gene expression studies on dietary-induced hyperlipidemia because they have a similar anatomy and digestive physiology to humans, and blood samples can be obtained from them repeatedly.
    Methodology: Two typical dietary treatments were used for dietary-induced hyperlipidemia models, by using specific pathogen-free (SPF) Clawn miniature pigs. One was a high-fat and high-cholesterol diet (HFCD) and the other was a high-fat, high-cholesterol, and high-sucrose diet (HFCSD). Microarray analyses were conducted from whole blood samples during the dietary period and from white blood cells at the end of the dietary period to evaluate the transition of expression profiles of the two dietary models.
    Principal Findings: Variations in whole blood gene expression intensity within the HFCD or the HFCSD group were in the same range as the controls provide with normal diet at all periods. This indicates uniformity of dietary-induced hyperlipidemia for our dietary protocols. Gene ontology-(GO) based functional analyses revealed that characteristics of the common changes between HFCD and HFCSD were involved in inflammatory responses and reproduction. The correlation coefficient between whole blood and white blood cell expression profiles at 27 weeks with the HFCSD diet was significantly lower than that of the control and HFCD diet groups. This may be due to the effects of RNA originating from the tissues and/or organs.
    Conclusions: No statistically significant differences in fasting plasma lipids and glucose levels between the HFCD and HFCSD groups were observed. However, blood RNA analyses revealed different characteristics corresponding to the dietary protocols. In this study, whole blood RNA analyses proved to be a useful tool to evaluate transitions in dietary-induced hyperlipidemia gene expression profiles in miniature pigs.

    DOI

    Scopus

    7
    被引用数
    (Scopus)
  • Whole Blood RNA analysis, Aging and Desease

    Takahashi, J, Takatsu, A, Misawa, M, Iwahashi, H

    Blood Cell - An Overview of Studies in Hematology   6   DOI:10.5772/48226  2012年  [査読有り]  [招待有り]

  • Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations

    Masaki Misawa, Junko Takahashi

    NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE   7 ( 5 ) 604 - 614  2011年10月  [査読有り]

     概要を見る

    The radiosensitizing effect of 5-250 nm diameter Au nanoparticles (AuNPs) in water was investigated under irradiations of diagnostic x-ray and UV light. Enhanced generations of hydroxyl radical ((center dot)OH) and superoxide anion (O(2)(-)) were confirmed from their dependencies on the absorbed energy, ethanol concentration and AuNPs&apos; concentration. Two kinds of fluorescent probes revealed that the reactive oxygen species (ROS) generation rate under x-ray irradiation was enhanced by factors of 1.46 for (center dot)OH and 7.68 for O(2)(-). Photo-and Auger electron charge transfer is possibly relevant to generation of O(2)(-) near the particle surface, whereas fluorescent x-rays are involved in generation of (center dot)OH in the secondary water radiolysis. Smaller diameter AuNPs with larger surface area showed a greater yield of ROS. An inverse proportion of ROS generation to the AuNPs&apos; diameter suggests a catalytic function of AuNPs&apos; surface for enhanced ROS generation.
    From the Clinical Editor: This paper investigates the effects of UV and X-ray irradiation on reactive oxygen species induction of gold nanoparticles, concluding that smaller diameter AuNPs with larger surface area lead to a greater yield of ROS probably due to catalytic effects. The paper may be important for the development of novel non-toxic radiation sensitizers. (C) 2011 Elsevier Inc. All rights reserved.

    DOI

    Scopus

    241
    被引用数
    (Scopus)
  • Oligonucleotide Microarray Analysis of Age-Related Gene Expression Profiles in Miniature Pigs

    Junko Takahashi, Masaki Misawa, Hitoshi Iwahashi

    PLOS ONE   6 ( 5 )  2011年05月  [査読有り]

     概要を見る

    Miniature pigs are useful model animals for humans because they have similar anatomy and digestive physiology to humans and are easy to breed and handle. In this study, whole blood microarray analyses were conducted to evaluate variations of correlation among individuals and ages using specific pathogen-free (SPF) Clawn miniature pigs. Whole blood RNA is easy to handle compared to isolated white blood cell RNA and can be used for health and disease monitoring and animal control. In addition, whole blood is a heterogeneous mixture of subpopulation cells. Once a great change occurs in composition and expressing condition of subpopulations, their associated change will be reflected on whole blood RNA. From 12 to 30 weeks of age, fractions of lymphocytes, monocytes, neutrophils, eosinophils, and basophils in white blood cells showed insignificant differences with age as a result of ANOVA analysis. This study attempted to identify characteristics of age-related gene expression by taking into account the change in the number of expressed genes by age and similarities of gene expression intensity between individuals. As a result, the number of expressed genes was less in fetal stage and infancy period but increased with age, reaching a steady state of gene expression after 20 weeks of age. Variation in gene expression intensity within the same age was great in fetal stage and infancy period, but converged with age. The variation between 20 and 30 weeks of age was comparable to that among 30 weeks individuals. These results indicate that uniformity of laboratory animals is expected for miniature pigs after 20 weeks of age. Furthermore, a possibility was shown that whole blood RNA analysis is applicable to evaluation of physiological state.

    DOI

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    6
    被引用数
    (Scopus)
  • 連続的疲労負荷過程における血液中で発現する生理的疲労関連遺伝子の検討

    原田 暢善, 岩木 直, 高橋 淳子, 岩橋 均

    日本疲労学会誌   6 ( 2 ) 28 - 35  2011年

  • Characterization of reactive oxygen species generated by protoporphyrin IX under X-ray irradiation

    Junko Takahashi, Masaki Misawa

    RADIATION PHYSICS AND CHEMISTRY   78 ( 11 ) 889 - 898  2009年11月  [査読有り]

     概要を見る

    As a possible radiosensitizer candidate having biological compatibility, oncotropic property, and X-ray activation capability, contribution of protoporphyrin IX (PpIX) to enhanced generation of reactive oxygen species (ROS) under X-ray and UV irradiations were examined. To identify the kinds of ROS, 2-[6-(4-amino)phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF) and dihydroethidium (DHE) were used together with ethanol as a hydroxyl radical (OH(center dot)) quencher. All of the three species of our interest (OH(center dot), superoxide radical (O(2)(center dot-)), and singlet oxygen ((1)O(2))) were enhanced by PpIX under X-ray and UV irradiations in addition to those by radiolysis and photolysis. Its enhancement factors exceeded 1.7 depending on the concentrations of PpIX from 1.5 to 15.0 mu g/ml. (C) 2009 Elsevier Ltd. All rights reserved.

    DOI

    Scopus

    41
    被引用数
    (Scopus)
  • 高圧食品加工技術の標準化に向けた標準微生物の提案

    岩橋 均, 原田 暢善, 三澤 雅樹, 高橋 淳子, 大淵 薫, 山本 和貴, 笹川 秋彦, 小林 篤, 山崎 彬

    高圧バイオサイエンスとバイオテクノロジー   2 ( 1 ) 122 - 129  2008年

     概要を見る

    高圧食品加工技術は、基礎研究から実用化の段階まで広く研究されており、その技術は社会的にも受け入れられ始めている。今後は、その普及を加速する必要があり、高圧食品加工技術の標準化が求められている。そこで、標準化の一環として、高圧殺菌の標準となる、指標微生物の調整法の標準化を検討している。本論文では、標準情報原案という形で、その内容を提案し広く意見を求めることにした。

    CiNii

  • Analysis of potential radiosensitizing materials for x-ray-induced photodynamic therapy

    Junko Takahashi, Masaki Misawa

    Nanobiotechnology   3 ( 2 ) 116 - 126  2007年05月  [査読有り]

     概要を見る

    For a development of deep tumor treatment in photodynamic therapy, a feasibility of novel radiosensitizers induced by x-ray was investigated. The sensitizers are designed to generate reactive oxygen species (ROS) inside or outside the cell, possibly leading to damage exclusively on tumor cells and reservation of normal cells along the x-ray path. Taking note of the similarity in energy transfer mechanism in photocatalysts, scintillators, and particulate semiconductors, we chose TiO2, ZnS:Ag, CeF3, and quantum dots (CdTe and CdSe) in particulate form, which contain heavy atoms for efficient absorption of x-rays. A parameter study for x-ray operating conditions showed that in a typical scenario, photons with 20 to 170 keV energy are attenuated by 90% through the region of particle dispersed aqueous solution at varying concentration between 0.01 and 100 wt%. The amount of ROS generation under the exposure of polychromatic x-ray was measured using dihydroethidium reagent which detects an integrated amount of several species. Proportional increase in ROS generation to x-ray dose was observed for varying concentrations of TiO2, ZnS:Ag, CeF3, and CdSe quantum dot dispersions. Then, HeLa cells were mixed with aqueous solutions dispersed with sensitizing materials at a concentration of 3.0 mg/ml and were exposed to x-ray. Their survival fraction obtained by a cell proliferation reagent WST-1 immediately after the irradiation showed insignificant effects of sensitizing materials except at large doses. To enhance the sensitization effect, bio-conjugated CdSe quantum dots were internalized in the cytoplasm up to a concentration of 1.0 ng/ml. The cells were irradiated by x-ray up to 5 Gy, and their survival fraction was measured by the colony forming ability 9 days after irradiation. Survival fraction of the cells treated with quantum dots were less than those without quantum dots for all doses, suggesting that the colony forming ability is impaired by the internalized quantum dots. © 2008 Humana Press Inc.

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    42
    被引用数
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  • Flexible manipulation of microfluids using optically regulated adsorption/desorption of hydrophobic materials

    Hidenori Nagai, Takashi Irie, Junko Takahashi, Shin-ichi Wakida

    BIOSENSORS & BIOELECTRONICS   22 ( 9-10 ) 1968 - 1973  2007年04月  [査読有り]

     概要を見る

    To realize highly integrated micro total analysis systems (mu TAS), a simply controlled miniaturized valve should be utilized on microfluidic device. In this paper, we describe the application of photo-induced super-hydrophilicity of titanium dioxide (TiO2) to microfluidic manipulation. In addition, we found a new phenomenon for reversibly converting the surface wettability using a polydimethylsiloxane (PDMS) matrix and the photocatalytic properties of TiO2. While PDMS polymer was irradiated with UV, it was confirmed that hydrophobic material was released from the polymer to air. Several prepolymers were identified as the hydrophobic material with a gas chromatograph and mass spectrometer (GUMS). Here, we successfully demonstrated the flexible manipulation of microfluid in a branched microchannel using the reversible wettability as micro opto-switching valve (MOS/V). The simultaneous control of MOS/Vs was also demonstrated on a 256-MOS/V integrated disk. The MOS/V promises to be one of the most effective flow switching valves for advanced applications in highly integrated micro/nano fluidics. (c) 2006 Elsevier B.V. All rights reserved.

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    35
    被引用数
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  • Response of Saccharomyces cerevisiae to a monoterpene: evaluation of antifungal potential by DNA microarray analysis

    M Parveen, MK Hasan, J Takahashi, Y Murata, E Kitagawa, O Kodama, H Iwahashi

    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY   54 ( 1 ) 46 - 55  2004年07月  [査読有り]

     概要を見る

    Plant-derived essential oils with monoterpenoids have been used as antifungal drugs since ancient times, but the mode of action of these natural hydrocarbons at the molecular level is not understood. In order to understand the mechanisms of toxicity of alpha-terpinene (a cyclic monoterpene), a culture of Saccharomyces cerevisiae was exposed to 0.02% alpha-terpinene for 2 h and transcript profiles were obtained using yeast DNA arrays. These profiles, when compared with transcript profiles of untreated cultures, revealed that the expression of 793 genes was affected. For 435 genes, mRNA levels in treated cells compared with control cells differed by more than two-fold, whereas for 358 genes, it was &lt;0.5-fold. Northern blots were performed for selected genes to verify the microarray results. Functional analysis of the up-regulated genes indicates that, similar to commonly used antifungal drugs, alpha-terpinene exposure affected genes involved in ergosterol biosynthesis and sterol uptake. In addition, transcriptional induction of genes related to lipid metabolism, cell wall structure and function, detoxification and cellular transport was observed in response to terpinene toxicity. Notably, the functions of 192 up-regulated genes are still unknown, but their characterization will probably shed light on the mechanisms of drug resistance and sensitivity. Taken together, this study showed that alpha-terpinene has strong antifungal activities and its modes of action resemble those of presently used antifungal drugs.

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    91
    被引用数
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  • Multiple reporter gene assays for the assessment and estimation of chemical toxicity.

    Takahashi J, Iwahashi H

    Environ Sci   11 ( 5 ) 269 - 282  2004年  [査読有り]

  • Effects of the pesticide thiuram: Genome-wide screening of indicator genes by yeast DNA microarray

    E Kitagawa, J Takahashi, Y Momose, H Iwahashi

    ENVIRONMENTAL SCIENCE & TECHNOLOGY   36 ( 18 ) 3908 - 3915  2002年09月  [査読有り]

     概要を見る

    Although there have been studies on the toxicity of the pesticide thiuram, the present study is the first one to attempt to integrate a whole genomic response using microarray technology. From the DNA microarray experiment, it was found that exposure to thiuram led to alterations of gene expression in yeast cells and that many genes involved in detoxification and stress response were highly induced. The induced genes were classified according to the MIPS yeast database. The induction of genes concerned with folding and proteolysis reflects the protein denaturing and degradation effects of the thiuram treatment. The induction of genes involved in redox and defense against reaction oxygen species also suggests that thiuram has other effects, such as oxidative stress. Genes classified for carbohydrate metabolism and energy were also highly induced, and these gene products may play the role of providing the energy for the detoxification mechanism. In addition, in view of the induction of some genes involved in DNA repair, thiuram potentially causes DNA damage. Therefore, as stated in previous reports, thiuram is a potential positive toxic chemical. On the other hand, YKL071W, YCR102C, YLR303W, and YLL057C were selected based on the result of a DNA microarray experiment and used for the promoter activity assay. Thiuram treatment affected the promoter of these genes, indicating that this technique could be used for the selection of biomarker candidates.

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    42
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  • モルモットの動脈硬化モデルにおける血漿の脂質成分および自己蛍光の測定

    高橋 淳子, 佐藤 正明

    脈管学   38 ( 11 ) 785 - 794  1998年11月

    CiNii

  • ヒト血漿の自己蛍光の特徴および酸化による蛍光の変化の検討

    高橋 淳子, 佐藤 正明

    脈管学   38 ( 2 ) 109 - 116  1998年02月

    CiNii

  • 血液透析器の溶質除去特性と生体適合性:―透析器膜素材の影響について―

    高橋 淳子

    昭和医学会雑誌   53 ( 5 ) 465 - 475  1993年

     概要を見る

    血液透析に使用する透析膜には高い溶質透過性と適度な除水性能を持つ再生セルロースが使用されてきたが, 同膜の持つ強い補体活性化作用が, 種々の悪影響を生体に及ぼす可能性が指摘されている.補体活性化作用を減弱させるため, 同膜の補体活性基をアセチル化したcellulose diace-tate (CA) 膜や3級アミンで置換したhemophan (H) 膜などが開発された.一方, 補体活性化作用が軽度な合成高分子polymethylmethacrylate (PMMA) 膜が早くから実用化されている.しかし, PMMA膜においては, 同膜のもつ陰性荷電がリンなどの陰性荷電を持つ貯留物質の除去性能を阻害する可能性が懸念されている.そこでこれらの補体活性化作用の軽度な膜素材透析器使用時の溶質除去能と生体の反応 (生体適合性) を臨床的に比較検討した.10名の安定期血液透析患者に, in vitroの尿素クリアランスに差のないH, CA, PMMA膜透析器を同一条件下にクロスオーバーで使用し, 溶質除去能, 各種生体適合性の指標を検討した.溶質除去能では, BUN, クレアチニン, 尿酸のクリアランス・除去率に3種の透析器間で差はなかったのに対し, リンのクリアランス・除去率はPMMAで有意の低値を示した.またリンのクリアランスはHで最も高値であった.透析中の血球数の変化では, 白血球減少はHでCAに比し有意に高度であったが, 血小板数の変化に透析膜間の差はみられなかった.Thromboxane B2, 6-ketoprostaglandin F1αの変化に3膜間で差はなかったが, β-thromboglobulinの静脈側/動脈側濃度比は開始後30分でCA, PMMAに比しHで有意の高値をとった.透析中の顆粒球エラスターゼ上昇はPMMAで有意に高度であった.Hでは透析開始後30分のセライト活性化凝固時間の延長が軽度で, fibrinopeptide Aの上昇が高度であった.以上の成績から, リンの除去性能は膜表面荷電の影響を受け, PMMAでは強い陰性膜荷電によりリン除去能が低く, Hでは相対的陽性荷電から除去能は増加した.また生体適合性ではPMMAは強い顆粒球活性化作用を持つ.Hは陽性荷電から血小板活性化作用が強く, 陽性荷電が直接的にヘパリンを吸着し, 凝固系活性化をもたらすと考えられた.

    DOI CiNii

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Misc

  • 抗体リポソームによる金ナノ粒子放射線増感剤の細胞取込み

    三澤 雅樹, 大森 拓也, 清水 森人, 佐藤 昌憲, 松本 孔貴, 高橋 淳子

    日本DDS学会学術集会プログラム予稿集   33回   181 - 181  2017年06月

  • X線照射による金ナノ粒子の増感作用と細胞ストレス応答

    三澤 雅樹, 早野 将史, 清水 森人, 佐藤 昌憲, 松本 孔貴, 高橋 淳子

    日本DDS学会学術集会プログラム予稿集   32回   178 - 178  2016年06月

  • 職歴を振り返って(女性研究者のキャリアを考える)

    高橋 淳子

    生物工学会誌 : seibutsu-kogaku kaishi   89 ( 10 ) 621 - 622  2011年

    CiNii

  • 1104 マイクロX線CTによる再生骨軟骨の構造評価(OS13-(5)オーガナイズドセッション《生体医工学及びバイオマテリアル》)

    三澤 雅樹, 林 和彦, 白崎 芳夫, 高橋 淳子

    茨城講演会講演論文集   2010 ( 0 ) 307 - 308  2010年

     概要を見る

    Bone-cartilage bi-phase element was constructed of native chondrocyte of beagle and P-TCP scaffold block. Assembling such a regenerative element enables to form arbitral configuration which fits the shape of large defect on joints without sacrificing other part of the body. The bone-cartilage bi-phase element was grafted in a distal femur condyle of a beagle for 2 month. The extracted femur sample including the bi-phase element was scanned by a high-resolution, micro-focus X-ray tomography to investigate the fusion process in vivo. The 3D tomography measurement showed that the hosting cancellous bone intruded into the scaffold and a part of the scaffold was replaced with the cancellous bone. Mechanical properties of grafted element was evaluated by a push-out test, indicating that scaffold was firmly fused with the cancellous bone of the host. Also, a preliminary microarray gene expression analysis was conducted to investigate the effect of X-ray radiation on the regenerative devices.

    CiNii

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