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World Journal of Gastroenterology 2007年第5期13卷 692-698页

作者： makoto mitsunaga Akihito Tsubota Kohichi Nariai Yoshihisa Namiki makoto Sumi Tetsuya Yoshikawa Kiyotaka Fujise Institute of Clinical Medicine and Research Jikei University School of Medicine Kashiwa Chiba Japan Division of Gastro-enterology and Hepatology Department of Internal Medicine Jikei University School of Medicine Tokyo Japan Institute of Clinical Medicine and Research Jikei University School of Medicine Kashiwa Chiba Japan

AIM： To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na （Ⅱ）. METHODS： HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin Ⅴ assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS： Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-xL, were decreased in Bax- and p53-independent manner. CONCLUSION： Our results indicate that eady apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na （Ⅱ） are mediated by p53- Bax network and low levels of Bcl-2 and Bcl-xL proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

关键词： Photodynamic therapy ATX-S10Na (Ⅱ) Apoptosis Bax p53

Dermatomyositis associated with hepatocellular carcinoma in an elderly female patient with hepatitis C virus-related liver cirrhosis

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World Journal of Gastroenterology 2006年第10期12卷 1641-1644页

作者： Nobuyuki Toshikuni Rikako Torigoe Mikio mitsunaga Akiyoshi Omoto Koji Nakashima Department of Internal Medicine Ako Central Hospital AkoJapanDepartment of Internal MedicineHimeji Red Cross HospitalHimejiJapan Department of Dermatology Ako Central Hospital AkoJapan Department of Internal Medicine Ako Central Hospital AkoJapan

A 79-year-old female patient with hepatitis C virusrelated liver cirrhosis was diagnosed as having hepatocellular carcinoma （HCC） with a diameter of 2.0 cm. She refused therapy for HCC. Nine months after the diagnosis, she developed dermatomyositis when the HCC enlarged to a diameter of 6.0 cm. She underwent therapy for dermatomyositis, and then transcatheter arterial chemoembolization for HCC. Although the manifestations of dermatomyositis improved and entire tumor necrosis was achieved, she died of pneumonia 2 mo after the treatment of HCC. HCC and/or chronic hepatitis C virus infection might be involved in the pathogenesis of dermatomyositis.

关键词： Dermatomyositis Hepatocellular carcinoma Hepatitis C virus

Comparison of cerebral activation between motor execution and motor imagery of self-feeding activity

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Neural Regeneration Research 2021年第4期16卷 770-774页

作者： Moemi Matsuo Naoki Iso Kengo Fujiwara Takefumi Moriuchi Daiki Matsuda Wataru mitsunaga Akira Nakashima Toshio Higashi Unit of Medical Science Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan Center for Child Mental Health Care and Education Nagasaki UniversityNagasakiJapan Department of Rehabilitation Faculty of Health SciencesTokyo Kasei UniversitySaitamaJapan Zeshinkai General Incorporated Association Nagasaki Rehabilitation HospitalNagasakiJapan The Japanese Red Cross Nagasaki Genbaku HospitalNagasakiJapan Unit of Rehabilitation Nagasaki University HospitalNagasakiJapan

Motor imagery is defined as an act wherein an individual contemplates a mental action of motor execution without apparent *** practice executed by repetitive motor imagery can improve motor performance without simultaneous sensory input or overt *** aimed to investigate cerebral hemodynamics during motor imagery and motor execution of a self-feeding activity using *** study included 21 healthy right-handed *** self-feeding activity task comprised either motor imagery or motor execution of eating sliced cucumber pickles with chopsticks to examine eight regions of interest:pre-supplementary motor area,supplementary motor area,bilateral prefrontal cortex,premotor area,and sensorimotor *** mean oxyhemoglobin levels were detected using near-infrared spectroscopy to reflect cerebral *** mean oxyhemoglobin levels during motor execution were significantly higher in the left sensorimotor cortex than in the supplementary motor area and the left premotor ***,significantly higher oxyhemoglobin levels were detected in the supplementary motor area and the left premotor area during motor imagery,compared to motor *** motor area and premotor area had important roles in the motor imagery of self-feeding ***,the activation levels of the supplementary motor area and the premotor area during motor execution and motor imagery are likely affected by intentional cognitive *** of cerebral activation differed in some areas during motor execution and motor imagery of a self-feeding *** study was approved by the Ethical Review Committee of Nagasaki University(approval No.18110801)on December 10,2018.

关键词： Activities of Daily Living brain function hemodynamics imagery(psychotherapy) mental practice motor cortex near-infrared neuroimaging neuroscience rehabilitation spectroscopy

An overview of Japanese cosmetic acupuncture

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World Journal of Acupuncture-Moxibustion 2022年第1期32卷 85-88页

作者： Kozue Orihashia Hiroyuki mitsunaga Masateru Kawai Hiroyasu Kitagawa Ang Zhou Yu Tan Bishinkai Tokyo 108-0071Japan Seirin Corporation Sizhioka 424-0037Japan Sichuan Yuanquan Technology Co. LtdChengdu 610041China

Objective:To provide an overview of Japanese cosmetic acupuncture and promote its ***:The study retrieved original and conference papers on cosmetic acupuncture published in the Japana Centra Revuo Medicina and summarized relevant operation techniques,indications,and other pertinent ***:A total of 163 related papers were retrieved,which focused on the treatment of 12 dermatological conditions including wrinkles and *** not only utilized acupuncture,but also incorporated other techniques,including cupping therapy,scraping therapy,pulse therapy,aromatherapy,exercise,and *** the treatments were guided either by Chinese medicine or western medicine ***:Cosmetic acupuncture has progressed rapidly in Japan in the past two decades and shows promising future developmental prospects.

关键词： Cosmetic Wrinkles Pigmentation Acupuncutre Japan

A Sensitive and Simple Method to Assess NK Cell Activity by RT-qPCR for Granzyme B Using Spleen and Blood

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Journal of Biosciences and Medicines 2021年第3期9卷 27-38页

作者： Fusako mitsunaga Shin Nakamura Intelligence and Technology Lab Inc. Kaizu Japan Biomedical Institute NPO Primate Agora Kaizu Japan

A new assay method for natural killer (NK) cell activity was established using quantitative RT-PCR (RT-qPCR) to determine the gene expression of granzyme B (GzmB) and perforin 1 (Prf1). The RT-qPCR method was compared to a conventional cytotoxic assay. Upregulated expression of GzmB and Prf1 mRNA and enhanced cytotoxic activity were observed in splenocytes from lipopolysaccharide (LPS)-treated rats. A high correlation, R2 = 0.71, was observed between the gene expression of GzmB and the cytotoxic activity of splenocytes from these rats, indicating that GzmB RT-qPCR is a reliable alternative method to assess NK cell activity/activation. Remarkably, 12.6- to 59.7-fold upregulation of GzmB mRNA expression was observed in leukocytes, the spleen, and splenocytes from LPS-injected rats. Its upregulation appeared to be dose-dependent on the LPS concentration in the range of 0.01 - 0.1 mg/kg. Whereas, only 1.3- to 1.9-fold increase of cytotoxic activity was detected in splenocytes from the rats treated with LPS in the same range. From these, it is evident that, to assess NK cell activity/activation, the GzmB RT-qPCR method is highly sensitive compared with the conventional cytological assay. Furthermore, this GzmB RT-qPCR method is advantageous, as it does not require freshly prepared splenocytes and cell culture procedures. The convenience of GzmB RT-qPCR enables the use of whole blood, leukocytes, the spleen, and/or their frozen samples to evaluate NK cell activity/activation.

关键词： NK Activation Functional Foods Immunostimulatory Effect mRNA Frozen Samples

A method for using video presentation to increase the vividness and activity of cortical regions during motor imagery tasks

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Neural Regeneration Research 2021年第12期16卷 2431-2437页

作者： Kengo Fujiwara Masatomo Shibata Yoshinaga Awano Koji Shibayama Naoki Iso Moemi Matsuo Akira Nakashima Takefumi Moriuchi Wataru mitsunaga Toshio Higashi Department of Clinical Services Nagasaki Rehabilitation HospitalNagasakiJapan Graduate School of Biomedical Sciences Nagasaki UniversityNagasakiJapan Department of Rehabilitation Faculty of Health SciencesTokyo Kasei UniversityTokyoJapan

In recent years,mental practice(MP)using laterally inverted video of a subject’s non-paralyzed upper limb to improve the vividness of presented motor imagery(MI)has been shown to be effective for improving the function of a paralyzed upper ***,no studies have yet assessed the activity of cortical regions engaged during MI task performance using inverse video presentations and neurophysiological *** study sought to investigate changes in MI vividness and hemodynamic changes in the cerebral cortex during MI performance under the following three conditions in near-infrared spectroscopy:MI-only without inverse video presentation(MI-only),MI with action observation(AO)of an inverse video presentation of another person’s hand(AO+MI(other hand)),and MI with AO of an inverse video presentation of a participant’s own hand(AO+MI(own hand)).Participants included 66 healthy right-handed adults(41 men and 25 women;mean age:26.3±4.3 years).There were 23 patients in the MI-only group(mean age:26.4±4.1 years),20 in the AO+MI(other hand)group(mean age:25.9±5.0 years),and 23 in the AO+MI(own hand)group(mean age:26.9±4.1 years).The MI task involved transferring 1 cm×1 cm blocks from one plate to another,once per second,using chopsticks held in the non-dominant *** on a visual analog scale(VAS),MI vividness was significantly higher in the AO+MI(own hand)group than in the MI-only group and the AO+MI(other hand)group.A main effect of condition was revealed in terms of MI vividness,as well as regions of interest(ROIs)in certain brain areas associated with motor *** data suggest that inverse video presentation of a person’s own hand enhances the MI vividness and increases the activity of motor-related cortical areas during *** study was approved by the Institutional Ethics Committee of Nagasaki University Graduate School of Biomedical and Health Sciences(approval No.18121303)on January 18,2019.

关键词： action observation cortical activity inverse video presentation mental practice motor imagery motor palsy paralysis recovery rehabilitation stroke

Anti-Allergic Effect of Para-Probiotics from Non-Viable Acetic Acid Bacteria in Ovalbumin-Sensitized Mice

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Food and Nutrition Sciences 2018年第12期9卷 1376-1385页

作者： Shin Nakamura Fusako mitsunaga Intelligence & Technology Lab Inc. Kaizu Japan Biomedical Institute NPO Primate Agora Inuyama Japan

Para-probiotics are ghost probiotics and consist of non-viable microbial cells. Here, a genus of acetic acid bacteria (AAB) was lyophilized to produce a para-probiotic preparation of non-viable (NV) AAB. The NV-AAB orally administered for 49 days ameliorated antigen-induced sneezing and plasma antigen-specific IgE in an ovalbumin-sensitized allergic mouse model. Our findings indicated that NV-AAB, as a para-probiotic functional food, exhibits an anti-allergic effect. The anti-allergic mechanism of NV-AAB was atypical because of the near-absence of an effect on Th1 and Th2 balance in splenocytes. NV-AAB will be a unique para-probiotic food material with an anti-allergic activity.

关键词： Probiotics Dead Cell Functional Food Treg IgE

Practical Use of Acoustic Rhinometry for Quantitative Assessment of Nasal Obstruction in an Allergic Model Using Macaque Monkeys

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Journal of Biosciences and Medicines 2017年第11期5卷 27-32页

作者： Fusako mitsunaga Shin Nakamura Motofumi Ohki Kaizu Laboratory Biomedical Institute NPO Primate Agora Kaizu Japan Intelligence and Technology Lab Inc. Kaizu Japan Biomedical Institute NPO Primate Agora Inuyama Japan Department of Otorhinolaryngology Kitasato University Medical Center Kitamoto Japan

Nasal obstruction, a primary symptom of allergic rhinitis, results in breathing difficulties and decreases quality of life in patients. Quantitative methods are required for diagnosis of nasal obstruction to accurately assess drug efficacy, not only in patients but also in animal models. Acoustic rhinometry is a non-invasive technique to measure nasal airway patency using acoustic reflections. To date, little information on its application in non-human primates (NHP) has been accumulated. Macaque monkeys are a practical NHP model because of their high similarity with humans in their biomedical nature, including genomic and immunologic events and morphology. We established an allergic rhinitis model of cynomolgusmacaque (Macaca fascicularis) sensitized with Japanese cedar pollen and applied acoustic rhinometry to measure nasal congestion. The extent of nasal congestion followed by allergen challenge was successfully quantified as the minimal cross-sectional area (MCA) of the nasal passage for the first time in an NHP allergic model. We also applied this acoustic technique to evaluate the efficacy of an antihistamine drug, fexofenadine. The acoustic assessment achieved quantitative evaluation of the efficacy of fexofenadine on nasal congestion in a macaque allergic model.

关键词： Non-Human Primate Pollinosis Nasal Congestion Allergic Rhinitis Antihistamine

Isolation, Identification and Tyrosinase Inhibitory Activities of the Extractives from Allamanda cathartica

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Natural Resources 2011年第3期2卷 167-172页

作者： Kosei Yamauchi Tohru mitsunaga Irmanida Batubara 不详

Tyrosinase inhibitory activity of the extractives from A. cathartica was examined and their new bioactivity and potent active compounds were identified. Five compounds, glabridin, new lignan, kaempferol, naringenin, and allamandicin, were isolated by a series of chromatography, and identified by NMR and LC-MS. Among them, glabridin had the high-est tyrosinase inhibitory activity (IC50:2.93 μM) which is 15 times stronger than that of kojic acid used as positive con-trol (IC50:43.7 μM). Moreover the lignan was indentified as 1-[3-(4-allyl-2,6-dimethoxyphenoxy)-4-methoxyphenyl] propane-1,2,diol which was a novel lignan.

关键词： Allamanda c athartica Tyrosinase Glabridin Kaempferol Naringenin Allamandicin

Risk management of cosmetic acupuncture

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World Journal of Acupuncture-Moxibustion 2020年第4期30卷 300-303页

作者： Kozue Orihashi Hiroyuki mitsunaga Mari Okamoto Mitsuhiro Kawabata Ryo Hasegawa Kazue Nakamura Yu TAN Masateru Kawai Hiroyuki Kitagawa Ang ZHOU Bishinkai Tokyo 108-0071Japan Medical Cosmetic Acupuncture Association Tokyo 106-0045Japan Anti-Aging Biyouhari Kenkyukai Nagoya city 466-0023Japan Seirin corporation Sizhioka city 424-0037Japan Sichuan Yuanquan Technology Co. LtdChengdu 610041China

In order to guarantee the clinical safety of cosmetic acupuncture,all kinds of potential risks are clarified and *** organizations for cosmetic acupuncture training have conducted the investigation on the risk of cosmetic acupuncture *** investigation contents have been collected to be a *** focuses on 12 treatment items that may cause the risks in cosmetic acupuncture and 3 treatment items that is coincident with cosmetic *** potential risks are summarized in clinical practice under the risk management of cosmetic acupuncture.

关键词： Acupuncture Cosmetic Safety Risk