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LactobacilliEnjoyed Fermented Herbs on to the Last Fragment and Regulated Leucocyte Subsets and Anti-Oxidative Activity

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Open Journal of Rheumatology and Autoimmune Diseases 2017年第1期7卷 30-45页

作者： Nobuo Yamaguchi Yoshiichiroh Mastuba Kazuhiro Okamoto daisuke sakamoto Takanao Ueyama Hideo Matsuno Nurmuhamamt Amat Ishikawa Natural Medicinal Products Research Center Ishikawa Japan Department of Rehabilitation Kanazawa Medical University Uchinada-Machi Japan Department of Heart Surgery Kanazawa Medical University Himi Municipal Hospital Himi Japan Department of 2nd Internal Medicine Kansai Medical University Osaka Japan Department of Otolaryngology Kanazawa Medical University Uchinada-Machi Japan Traditional Uighur Medicine Department Xinjiang Medical University Urumqi China

Eighty sorts of herbs were fermented by Lactobaccilli (f-ESH). This material was proved by as safe in animal safety experiment. This work was aimed to revise the traditional way of hot water extraction to the fermentation, in order to use up the original material and searching new activity as well. We tried to prove the new activity by fermentation for immune-competent cells in the host that administrated both of original remedy and the new fermented sample. In rodents, immune-compromised host was prepared with cancer chemotherapeutic agent. Our observations showed that the antigen stimulated animal increased the antibody producing cell for heterologous erythrocyte by compromised host by f-ESH. Moreover, by administration of f-ESH to immno-suppressed hosts, these samples regulated lymphocyte in number and functions, macrophage activities, and regulating anti-oxidative activity by phagocytic cells. The anti-oxidative assay was carried out ex-vivo system by peritoneal excaudate cell that we propose as suitable system for evaluating antioxidative assay. With these evidences, the original COF only augmented the level of lymphocytes in number, while f-ESH regulated the ratio of granulocytes and lymphocyte. In clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio was also resulted as neutral in peripheral white blood cells, 1, 2 and 3 weeks after the administration of f-ESH. We discussed the significance and mechanism of cleving complement components Fb by f-ESH in this text. Fb. The new cleavage of complement was directly evident by immune-electrophoretic method. In conclusion, this modification of food materials introduced new style of food intake resulted in the significant regulation such as antibody producing cells and anti-oxidative activity for phagocytic cells comparing traditional processing by hot water extraction.

关键词： Wild Herbs Fermentation Lactobacilli Lymphocyte Granulocyte Ant-Oxidative Activity GABA Complement Alternative Complement Activation

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Factors Affecting Japanese Pond Smelt (Hypomesus nipponensis) Stock Trajectory in Lake Kasumigaura and Kitaura

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Open Journal of Marine Science 2015年第2期5卷 210-225页

作者： Ashneel Ajay Singh Noriyuki Sunoh Shintaro Niwa Fumitaka Tokoro daisuke sakamoto Naoki Suzuki Kazumi Sakuramoto Department of Ocean Science and Technology Tokyo University of Marine Science and Technology TokyoJapan Freshwater Branch Office Ibaraki Fisheries Research Institute Ibaraki Japan

The Japanese pond smelt (Hypomesus nipponensis) stock has been observed to fluctuate quite rigorously over the years with sustained periods of low catch in Lake Kasumigaura and Kitaura of the Ibaraki prefecture, Japan which would adversely affect the socioeconomic livelihood of the local fishermen and fisheries industry. This study was aimed at determining the factors affecting the stock fluctuation of the pond smelt through the different years in the two lakes. Through exploratory analysis it was found that the pond smelt had significant relationship with total phosphorus (TP) level in both lakes. The global mean land and ocean temperature index (LOTI) was also found to be indirectly related to the pond smelt stock in lake Kasumigaura and Kitaura at the latitude band of 24°N to 90°N (l). Both TP and LOTI had inverse relationship with pond smelt trajectory in both lakes. For both Lake Kasumigaura and Kitaura, TP for the individual lakes and LOTI (l) were used as independent variables using generalized linear model and response surface methods for modeling the stock dynamics of the pond smelt in the two lakes. Model selection was based on significant parameter estimates (p < 0.05), Akaikes Information Criterion and R2 values. Phosphorus loading is an indication of increasing anthropogenic activities in the surrounding area having negative impact on the pond smelt population. When management decisions are being made regarding pond smelt fishery and sustainability plans in the Ibaraki prefecture, the effects of TP and LOTI should be taken into account. Future research needs to be directed towards deeper understanding the mechanisms by which TP and LOTI affect pond smelt population in Lake Kasumigaura and Kitaura for more effective management.

关键词： Pond Smelt Lake Kasumigaura Lake Kitaura Phosphorus Surface Temperature

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Regulative effect for natural killer cell by hot spring hydrotherapy—Quantitative and qualitative discussion

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Open Journal of Immunology 2013年第4期3卷 201-209页

作者： Nobuo Yamaguchi Wenhan Wan daisuke sakamoto Amat Nurmuhammad Kengo Matsumoto Takafumi Takei Katsuko Okuzumi Tsugiya Murayama Takashi Takahashi Deaprtment of Microbiology and Immunology Faculty of Pharmaceutical Sciences Hokuriku University Japan Department of Heart Surgery Kanazawa Medical University Himi Municipal Hospital Himi City Japan Ishikawa Medicinal Products Research Center Kanazawa Japan Ishikawa Medicinal Products Research Center Kanazawa Japan Laboratory of Infectious Diseases Graduate School of Infection Control Sciences Kitasato University Tokyo Japan Uighur Medicine Department of Xinjiang Medical University Urumqi City China

Along with maintaining immune competent cells, one of the purposes of cancer patient is regulating the first line of defense for survival. Moreover, the factors that influence the acquired immune activity are systemic metabolic disorder in diabetes, malnutrition, extreme exhaustion, stresses, aging and medical side effect such as chemotherapy. So we have to select appropriate menu to regulate immune function through leukocyte storage. Especially, NK cell is first line of defense against virus infected cell and/or tumor cell. In order to recommend the effect of hot spring hydrotherapy on the peripheral white blood cells as a parameter for complementary and alternative medicine (CAM) within a short period, the granulocytes, lymphocytes, lymphocyte subsets in their peripheral blood were monitored. In the young group (35 or less), the number of granulocytes clearly decreased after hydrotherapy. In the older group (over 35 years old), the total number of leukocytes and lymphocytes significantly increased after the therapy. Using a FACScan, we investigated CD2, CD4, CD8, CD16, CD19 and CD56 positive cell as well as the cytokine containing cell, as direct assessment for immunological preparation (IFN-γ, IL-4 and IL-1β). After hydrotherapy, the CD16+ cells also increased outstandingly. However, the CD19+ cells clearly decreased. Moreover, there was a decrease in the cytokine-producing cell count of subjects whose blood cells had a higher number of the cell level before. All of the results indicated that hot spring hydrotherapy could regulate the immune system even in normal human. Like this, blood hormonal level was measured in order to know the mechanism of the quantitative and qualitative, adjustment of the leucocytes becomes possible within a short term. As a result of measuring, 7 kinds of hormone including mainly adrenocortical hormones, adrenalin level reduced in constitution dependent manner. From these results, it was suggested that the quantitative and qualitative

关键词： Hot Spring Hydrotherapy Leukocyte Regulation NK Cell Quantitative Regulation of Lymphocyte Qualitative Regulation of Lymphocyte

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Quantitative regulation of peripheral leukocyte by light exercise and tailored scale for assessment

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Open Journal of Immunology 2013年第4期3卷 175-183页

作者： Nobuo Yamaguchi Rui Chen Kazuhiro Okamoto Takafumi Takei Misao Tsubokawa daisuke sakamoto Xiufeng Jia Wenhan Wan Tsugiya Murayama Deaprtment of Microbiology and Immunology Faculty of Pharmaceutical Sciences Hokuriku University Kanazawa Japan Department of Heart Surgery Kanazawa Medical University Himi Municipal Hospital Himi City Japan Department of Rehabilitation Kanazawa Medical University Uchinada-machi Japan Ishikawa Medicinal Products Research Center Kanazawa Japan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Two primary defense systems develop in vertebrates, innate and adaptive. However, every individual exposes to the risk of immunodeficiency in daily life with both internal and external stimuli. In this report, we tried to report two different stimuli for regulating the immune system modulate and discussed how we can compare and select each menu by evidence-based manner more than VAS. In a series of investigation, we have assessed the various leukocyte regulating menus such as hot spring hydrotherapy, acupuncture & moxibution, light walking, independent of the western medicine. In this report, we try to compare the regulatory effect of light exercise under the influence of hypothalamus system. Their effects of elements were evaluated by the total number of peripheral leukocyte, its subsets, granulocyte and lymphocyte ratio. The regulative effects were confirmed also by other menu such as hydrotherapy, acupuncture, walking etc. However, by simply comparing the group before with the group after CAM, we cannot catch the real regulatory effect by each menu. So we tried to show the effect by trying to indicate the constitution/condition dependent manner. The effect was not uniform to each individual but it was dependent on each condition/constitution before the start of the exercise. This was one of the main purposes of this report for summarizing that it is important to regulate the number and levels of each factor as ideal value. In other words, the regulation of each factor affected under the hypothalamus system is regulated with each constitution, under the influence of daily circumstances. The mode of regulation was the same in each menu, indicating the higher level was down regular and lower level was up regular. Moreover, each vector of change was reversely correlated to the value of the day before. The other purpose of this study was designed to establish the regulatory effect of this light exercise which is not limited in the number of leukocyte in peripheral. Li

关键词： Light Exercise Walking Peripheral Leukocyte Leukocyte Subsets Ratio Metabolic Rate

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Bi-Directional Regulation by Chinese Herbal Formulae to Host and Parasite for Multi-Drug Resistant Staphylococcus aureusin Humans and Rodents

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Open Journal of Immunology 2015年第1期5卷 18-32页

作者： Nobuo Yamaguchi Takanao Ueyama Nurmuhamamt Amat Dilxat Yimit Parida Hoxur daisuke sakamoto Yuma Katoh Ikkan Watanabe Shan-Yu Su Department of Fundamental Research for CAM Kanazawa Medical University Uchinada Japan Ishikawa Natural Medicinal Products Research Center Kanazawa Japan Department of Medicine II Kansai Medical University Osaka Japan Traditional Uighur Medicine Department Xinjiang Medical University Urumqi China Traditional Chinese Medicine Hospital Xinjiang Medical University Urumqi China Department of Chest Surgery Kanazawa Medical University Himi Citizen Hospital Himi Japan Department of Respiratory Medicine Tohkai Central Hospital Gifu Japan Department of Chinese Medicine China Medical University Hospital Taichung City Taiwan School of Post-Baccalaureate Chinese Medicine College of Chinese Medicine China Medical University Taichung City Taiwan

A decline in the immunopotential of the host plays acritical factor(s) in the occurrence of infections with methicillin-resistant Staphylococcus aureus (MRSA) or microorganisms by opportunistic infection. In such an infection, no way out for therapeutic concept, therefore bi-directional trial was the final choice. So we selected aformula, Dang Gui Liu Huang Tang (dLHT), which could both augmentimmune factorsin host and exert bacteriostatic effect. We sought to break through the epidemic by MRSA especially in elderly patient, by the fundamental and clinical trial by employing minor TCM, characterizing bidirectional ability of the decoction by western methods. Animal Experiment: Mitomycin-C (MMC)-treated mice with or without the infection of MRSA were made. The experimental design was made up to examine the bacteriostatic action as well as the immunopo-tentiating bias of the promising Chinese herbal medicine, dLHT, which was first proved for its immune potentiating activities as well as their sensitivity to antibiotics, but not direct aseptic effect was clear for MRSA. Both basic and clinical data showed that this formula was effective on repelling from the infectious focus after the treatment of MRSA infection. After the administration of dLHT, the number of white blood cells in MMC-treated mice recovered to 80% of the normal level. In addition, the phagocytic activity of macrophages increased to 70% in the dLHT-treated group, while that of the non-treated group was only 20%. The bactericidal activity also recovered to the level close to the normal value by dLHT. The ratio of neutrophils in the dLHT-administered group increased to 2.2% (normal mice, 2.6%), whereas that in the non-terated group was only 0.5%. The bacterial count in the liver of MRSA-challenged mice reached the peak at six hours after the challenge in both dLHT-treated and non-treated mice. However, the number of bacteria in dLHT group was much greater than that in the non-treated group. The bacterial

关键词： Drug Sensitivity Multiple Resistance Dang Gui Liu Huang Tang MRSA Nosocomical Infection Host Immunity

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Hemopoietic Formulae Rearranged Leukocyte Subsets and Implication for Use against the Type of Constitution and Infectious Agent for Further Modification to Future

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Open Journal of Immunology 2015年第3期5卷 183-198页

作者： Nobuo Yamaguchi Wataru Hiruma Kohei Suruga Nurmuhamamt Amat Dilxat Yimit Parida Hoxur daisuke sakamoto Kazuhiro Okamoto Shan-Yu Su Department of Fundamental Research for CAM Kanazawa Medical University Ishikawa Japan Ishikawa Natural Medicinal Products Research Center Ishikawa Japan International Operation Department (FM Center for R & D) Kibun Foods Inc. Tokyo Japan Traditional Uighur Medicine Department Xinjiang Medical University Urumchi China Traditional Chinese Medicine Hospital Xinjiang Medical University Urumchi China Department of Otolaryngology Kanazawa Medical University Ishikawa Japan Department of Chinese Medicine China Medical University Hospital Taiwan School of Post-Baccalaureate Chinese Medicine College of Chinese Medicine China Medicinal University Taiwan

A hemopoietic formula (HF) in traditional Chinese medicine (TCM) usually consists of more than six single herbs. We seek to look into changes of immune-competent cells by two commonly utilized HF, including Shi-Quan-Da-Bu-Tang (SDT) and Bu-Zong-Ye-Qi-Tang (BYT). However, the effects of both formulae on levels of leukocyte subsets are not yet defied. After administration of immno-suppressant to animals, the effects by HFs on the augmentation for subsets of leukocytes, CD positive cell counts of lymphocytes, and the cytokine-producing cells are measured. Our results show that SDT augments the level of lymphocytes, while BYT increases the level of granulocytes. In our clinical study with 15 healthy volunteers, positive cells for CD2, CD11b, CD14, IL-4, IL-1β and IFN-γ in peripheral blood are increased significantly 15 days after the ingestion of HFs. In rodents, compromised host as well as normal animal is administered with cancer chemotherapeutic agent (Mytomycin-C). Our observations show that SDT regulates phagocyte activities of the immune system, introducing it against intracellular parasite, and that BYT augments intercellular pathogen through humoral immunity. We discuss the significance and mechanism of HFs on the level of leukocyte subsets in number and function that are considered to be potential indicators for the evaluation of TCM modalities. We also propose an idea that TCM exhibits tonic effects via enhancing the ability to fight against infection and bacteria, as well as turning the multi-drug resistant bacteria to the sensitive ones. Together with these evidences, we suggest an ideal remedy for the compromised to fight host against pathogens. Moreover, we try to modify these hemopoietic formulae to more digestive forms. This modification brings to the significant lifted up for antibody producing cells and anti-oxidative activity for phagocytic cells.

关键词： Traditional Chinese Medicine Cancer Chemotherapeutic Agent Compromised Host Intracellular Infectious Agent Intercellular Infectious agent

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Recent updates of therapeutic strategy of esophagogastric junction adenocarcinoma

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 727-736页

作者： Suguru Maruyama Yu Imamura Yasukazu Kanie Kei sakamoto daisuke Fujiwara Akihiko Okamura JunKanamori Masayuki Watanabe Department of Gastroenterological Surgery Cancer Institute Hospital of Japanese Foundation of Cancer ResearchTokyo 135-8550Japan.

The incidence of esophagogastric junction(EGJ)adenocarcinoma has been increasing in Asian *** the recent advances in multidisciplinary treatments,EGJ adenocarcinoma remains aggressive with unfavorable *** surgical strategy,EGJ adenocarcinoma arises between the esophagus and the stomach,and thus tumor cells spread through the lymphatic system both upward to the mediastinum and downward to the ***,an optimal extent of lymphadenectomy remains *** drug therapy,the latest topic in gastric and EGJ adenocarcinoma is trastuzumab deruxtecan,which is an antibody-drug conjugate consisting of an anti-HER2 *** addition,many clinical trials have recently demonstrated the efficacy of immune checkpoint ***,recent advances in sequencing technology have revealed that gastroesophageal adenocarcinoma could be categorized into four molecular subtypes:epstein-Barr virus-associated,high-level microsatellite instability,genomically stable,and chromosomal instability ***,these subtypes show distinct clinical phenotypes and molecular *** review the current surgical strategy and drug treatment such as molecular-targeted agents,immune checkpoint inhibitors,and molecular-subtype-based therapeutic strategies in EGJ *** and molecular characteristics and response to immune checkpoint inhibitors differ among molecular *** strategies based on molecular subtypes may be clinically beneficial for patients with EGJ adenocarcinoma.

关键词： Esophagogastric junction adenocarcinoma Barrett’s esophagus microsatellite instability molecular subtype

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Decreased incidence followed by comeback of pediatric infections during the COVID‑19 pandemic in Japan

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World Journal of Pediatrics 2022年第8期18卷 564-567页

作者： Cyrus Ghaznavi Haruka sakamoto Takayuki Kawashima Sayaka Horiuchi Masahiro Ishikane Sarah Krull Abe daisuke Yoneoka Akifumi Eguchi Yuta Tanoue Masahiro Hashizume Shuhei Nomura Department of Health Policy and Management School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 160-8582Japan Medical Education Program Washington University School of Medicine in St.LouisSaint LouisUSA Department of Global Health Policy Graduate School of MedicineThe University of TokyoTokyoJapan Tokyo Foundation for Policy Research TokyoJapan Department of Hygiene and Public Health Tokyo Women’s Medical UniversityTokyoJapan Department of Mathematical and Computing Science Tokyo Institute of TechnologyTokyoJapan Center for Birth Cohort Studies University of YamanashiYamanashiJapan Disease Control and Prevention Center National Center for Global Health and MedicineTokyoJapan Division of Prevention National Cancer Center Institute for Cancer ControlTokyoJapan Infectious Disease Surveillance Center National Institute of Infectious DiseasesTokyoJapan Department of Sustainable Health Science Center for Preventive Medical SciencesChiba UniversityChibaJapan Institute for Business and Finance Waseda UniversityTokyoJapan

During the coronavirus disease 2019(COVID-19)pandemic,the Japanese government implemented several infection control measures,such as states of emergency(SoE)and school closures,and encouraged universal masking and hand *** activity restrictions and improved hygiene were found to be associated with declines in the incidence of infuenza during the 2019–2020 winter season[1].Prior studies have found that the incidence of seven pediatric infections,such as pharyngoconjunctivitis and varicella,decreased during and after the school closures in Japan[2].As activity restrictions continue to be lifted,there is growing concern that pediatric infections may suddenly return given that the pool of susceptible children increased during the pandemic[3].In this study,we use national infectious disease sentinel data from January 2012 to October 2021 to assess changes in the reported number of pediatric infections in Japan during the COVID-19 *** hypothesize that the reporting of many infectious diseases decreased during the early stages of the pandemic but ultimately returned to normal when activity restrictions were lifted.

关键词： closure return suddenly

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Molecular insights into colorectal cancer stem cell regulation by environmental factors

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Journal of Cancer Metastasis and Treatment 2015年第1期1卷 156-162页

作者： daisuke Izumi Takatsugu Ishimoto Yasuo sakamoto Yuji Miyamoto Hideo Baba Department of Gastroenterological Surgery Graduate School of Medical ScienceKumamoto University1-1-1 HonjoKumamoto 860-8556Japan Cancer and Stem Cell Biology Duke-NUS Graduate Medical School Singapore169857 Singapore.

Colorectal cancer remains a signifi cant cause of cancer-related mortality worldwide,mainly because of tumor relapse and *** stem cells(CSCs)are considered to be the main cause of resistance to chemotherapeutic agents,as well as being responsible for distant *** CSCs themselves possess innate abilities for self-renewal and differentiation,the environment surrounding CSCs provides oxygen,nutrients and secreted factors,and also supports angiogenesis,thus it's responsible for maintaining their CSC ***,extensive investigations have revealed that obesity,accompanied by excess visceral adipose tissue,induces chronic infl ammation,and is linked to the risk and progression of several gastrointestinal cancers,through modulating the capacities of the *** review presents the evidence linking colorectal CSCs and their environment and summarizes our current understanding of the molecular mechanisms underlying this relationship.

关键词： Cancer stem cells markers colorectal cancer stem cell nutrient obesity tumor microenvironment

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Is there diversity among UGT1A1 polymorphism in Japan?

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World Journal of Gastrointestinal Oncology 2012年第7期4卷 170-175页

作者： Michiya Kobayashi Shoichi Hazama Kenichi Takahashi Koji Oba Naoko Okayama Mitsuaki Nishioka Yuji Hinoda Masaaki Oka Ken Okamoto Hiromichi Maeda daisuke Nakamura Junichi sakamoto Hideyuki Mishima Department of Human Health and Medical Sciences Kochi Medical School Nankoku 783-8505 Japan Department of Digestive Surgery and Surgical Oncology (Surgery Ⅱ) Yamaguchi University Graduate School of Medicine Ube Yamaguchi 755-8505 Japan Department of Surgery Aomori Prefectural Central Hospital Aomori 030-8553 Japan Translational Research and Clinical Trial Center Hok-kaido University Hospital Sapporo 060-8638 Japan Division of Laboratory Yamaguchi University Hospital Ube Yamaguchi 755-8505 Japan Department of Oncology and Laboratory Medicine Yamaguchi University Graduate School of Medicine Ube Yama-guchi 755-8505 Japan Tokai University School of Medicine Is-ehara Kanagawa 259-1131 Japan Young Leaders Program in Healthcare Administration Nagoya University Graduate School of Medicine Nagoya 466-8550 Japan Department of Surgery Osaka National Hos-pital Osaka 565-0871 Japan

AIM: To investigate into the diversity of UGT1A1 polymorphism across three different districts in Japan and highlight genetic differences among the population in Japan. METHODS: We enrolled 50 healthy volunteers from each of the Yamaguchi (western part of Japan), Kochi(southern part of Japan) and Akita (northern part of Japan) prefectures. Blood samples (7 mL) were collected from each participant and stored in EDTA for subsequent genotyping by fragment size analysis, direct sequencing and TaqMan assay of UGT1A1*28, UGT1A7*3/UGT1A9*22 and UGT1A1*93/UGT1A1*6/ UGT1A1*27/UGT1A1*60/UGT1A7 (-57), respectively. RESULTS: The only statistically significant differences in allele polymorphisms among the group examined were for UGT1A1*6. The Akita population showed more UGT1A1*6 heterozygosity (P = 0.0496). CONCLUSION: Our study revealed no regional diversity among UGT1A1, UGT1A7 or UGT1A9 polymorphisms in Japan.

关键词： UGT1A1 gene Polymorphism Diversity

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