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Fermented Herbal Decoction Selectively Targeting Human Cancer Cell Line and Human Pathogenic Microorganism

Open Journal of Rheumatology and Autoimmune Diseases 2018年第1期8卷 17-33页

作者： Nobuo Yamaguchi Nurmuhammat Amat kazuhiro okamoto Tsugiya Murayama Ishikawa Natural Medicinal Product Research Center Kawakawa Japan Traditional Uyghur Medicine Institute Xingjian Medical University Urumqi China Department of Rehabilitation Kanazawa Medical University Uchinada Japan Department of Microbiology and Immunology Faculty of Pharmaceutical Sciences Hokuriku University Kanazawa Japan

Introduction: Prolonged immuno-suppressed status promised to induce internal growth of malignant cell and infectious agent, yet, only a small part of affected individuals seek medical attention or berried by commercially over-flowed fake information. Several studies have described complementary and alternative medicine as effective strategies for improving anti-infectious agent including malignant cell. The purpose of this study was to investigate the effect of a fermented herbal decoction (FHD) both in vitro and in vivo to malignant cells and microorganism by regulating leukocyte subset proportioning FHD as dietary material. Methods: In this approach of alternative study, selective anti-cancer effect by fermented decoction was tried to show first in vitro system both, cancer cell and virus strain. The fermented herbal decoction consisting of 80 sorts of herbs and fruits. The selective toxicity was set up and then for immunological factors in animal and human. The most important factor is to reduce side effect for a normal cell. Results: First, FHD was proved as safe by animal test. FHD regulated also the proportion of granulocyte and lymphocyte ratio both animal and human. In vitro culture showed selective toxicity by FHD against human melanoma and leukemia cell line but reduced toxicity was showed by normal cell line. As for the anti-virus activity, anti-virus effect was tested on the feeder layer of human fibroblast cell, after 9 days of culture. Second, FHD inhibits colon cancer growth in 3-methylholanthrene induced cancer in rat. Conclusion: The present results suggest that our fermented herbal decoction showed selective anti-cancer activities and anti-virus activities, together with the regulative effect on the immune system.

关键词： Fermented Herbal Decoction Human Malignant Cell Line Human Normal Cell Line Anti-Virus Activity 3-Methylholanthrene Experimental Colon Can-cer In Vitro In Vivo Anti-Cancer Trial

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Fermented Ethnic Medicine (Pueraria mirifica) Designed by Lactobacillus Regulated Leukocyte Subsets via Activation of Complement Components

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Open Journal of Rheumatology and Autoimmune Diseases 2017年第1期7卷 65-79页

作者： Yoshiichiroh Mastuba kazuhiro okamoto Yuma Kato Nobuo Yamaguchi Sumiyo Akazawa-Kudoh Ishikawa Natural Medicinal Products Research Center Ishikawa Japan Department of Rehabilitation Kanazawa Medical University Uchinada-machi Japan Department of General Medicine Kanazawa Medical University Ishikawa Japan

A plant fermentation was carried out by Lactobaccilli against the Rhizome from Pueraria milifica (f-PMF). This material was evidenced by safe in animal toxic study. The main aim of this study was to revise the traditional way of hot water extraction to fermentation so as to use up the original material and finding new activity. We tried to show the new activity through phytoestrogen and immune-competent cells from the host that administrated either of original remedy and the new fermented sample, plus activated water SRE. In mice, compromised host was prepared by cancer chemotherapeutic agent (Mitomycin-C). After administration of f-PMF to immno-suppressed animals, the effects by both samples were augmented by lymphocyte in number and functions, macrophage activities, anti-oxidative activity. However, the intense of effect was much more by fermented one but not by conventional one. The anti-oxidative assay was also carried out ex-vivo system by peritoneal macrophage that we proposed as suitable system for evaluating anti-oxidative assay. In our clinical study by 20 healthy volunteers, granulocyte and lymphocyte ratio was regulated as neutral in peripheral white blood cells, increasing one, two and three weeks after the administration of f-PMF. We have found the significant regulation of blood chemical factors that were important makers for the lifestyle-related diseases. The mechanism of augmentation by probing directory with immuno-electrophoretic method, generating new complement component, especially found by alternative pathway of complement. So we discussed the process concerning designed f-PMF molecule for activation of complement component and bound for the biological activity of each physical component. In a limited condition, fewer numbers of volunteers, the breast size was tending to increase along with the administration time. Including these evidences, we discussed the possibility of this traditional ethnic medicine, originally found and spread in the hi

关键词： Family Pueraria Fermentation Lactobacilli Cancer Chemotherapeutic Agent Immune-Compromised Host Lymphocyte Granulocyte Ant-Oxidative Activity Complement Alternative Complement Activation

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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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Overall Estimation of Anti-Oxidant Activity by Mammal Macrophage

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Open Journal of Rheumatology and Autoimmune Diseases 2014年第1期4卷 13-21页

作者： Nobuo Yamaguchi Natsuko Kawada Xinfeng Jia kazuhiro okamoto Katsuko Okuzumi Rui Chen Takashi Takahashi Department of Fundamental Research for CAM Kanazawa Medical University Ishikawa Japan Ishikawa Natural Medicinal Products Research Center Kanazawa Japan Kanazawa University Graduate School of Medical Science Kanazawa Japan Laboratory of Infectious Diseases Graduate School of Infection Control Sciences Kitasato University Tokyo Japan. Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Super oxide anion had been known as a critical role in a phagocytic cell when microorganisms invade inside. However, this radical seldom need for a clean environment such in a developed country. Moreover, this agent sometimes triggered as serious factor in the site of inflammation. There are many papers which concerned newly found anti-oxidative substances. However, many reports only focused on the molecular basis in vitro, how oxidative stress damaged the human tissue. The key factor for oxidative stress needs to be discussed first for immunological standpoint, such as armed reduction treaty. In other words, minimum armed force is necessary for an invasion by outer or inner irregular cells. On the basis of phagocytic function of the cell in vivo, we tried to access anti-oxidative activity by employing peritoneal murine macrophage and human monocyte. So, the purpose of this study is to establish a conventional but tailor made system for which is useful for evaluating the anti-oxidative activity to different constition. Especially in human peripheral monocyte, the sample was tested each constitution such in granulocyte rich type and lymphocyte rich typ. In order to establish the direct estimation by phagocytic cell, a murine peritoneal exudates cell suspension was obtained after one week of oral administration with anti-oxidative sample. The samples we selected were traditional Chinese medicine, Shi-Quan-Da-Bu-Tang (SDT), Bu-Zong-Ye-Qi-Tang (BYT) and Shao-Chin-Rong-Tang sCRT), Agaricus, Chlorella, and Propolis. The amount of generated super oxide anion was calculated through measuring the optical density change of this supernatant using cytochrome-C which was reduced by generated super oxide anion in the phagocytic cell. The generated super oxide anion after administration of Agaricus, Chlorella, SDT, BYT, sCRT and Propolis were 2.64, 1.95, 1.24, 1.25, 2.88, 2.55 × 10﹣5 mmol/ml, respectively, whereas 2.85 × 10﹣5 mmol/ml in control group. The fermented sample from SDT

关键词： Anti-Oxidant Sample Super Oxide Anion Neutrophil Macrophage Cytochrome-c Constitution

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Rodent Macrophage Select Vin Blank Together with Vin Rouge According to SO Level in Situ

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Open Journal of Rheumatology and Autoimmune Diseases 2014年第4期4卷 240-247页

作者： Nobuo Yamaguchi Keiko Matsuba kazuhiro okamoto Takanao Ueyama Yoshiichiroh Matsuba Katsuko Okuzumi Ikkan Watanabe Takashi Takahashi Department of Fundamental Research for CAM Kanazawa Medical University Uchinada Japan Ishikawa Natural Medicinal Products Research Center Kanazawa Japan Graduate School of Medical Science Kanazawa University Kanazawa Japan Department of Medicine II Kansai Medical University Osaka Japan Laboratories of Infectious Diseases Graduate School of Infection Control Sciences Kitasato University Tokyo Japan

Phagocytic cells are known as multi potent activities for its ontogenical and phylogenetical aspect. One of the strike actions is super oxide anion known as critical role of the cell when microorganisms invade inside the cytoplasm. This agent sometimes triggered as a serious factor in the site of inflammation. There are many papers which concerned newly accessed anti-oxidative substances. However, many reports only focused on the molecular basis in vitro, suggesting vin rouge for their rich content of polyphonol rather than vin blank with a French paradox. We had been suggested that the key factor for oxidative stress needs to be discussed first for immunological standpoint, such as in phagocytic cell in situ. With this assay system in rodent macrophage, SO level was about the same for both groups administered vin blank as well as vin rouge.

关键词： Super Oxide Anion Anti-Oxidant Sample Neutrophyl Macrophage Vin Blank Vin Rouge In Situ Estimation

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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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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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Hot Spring Hydro Therapy Regulates Peripheral Leukocyte Together with Emotional Hormone and Receptor Positive Lymphocytes According to Each Constitution/Condition

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Open Journal of Rheumatology and Autoimmune Diseases 2013年第3期3卷 140-153页

作者： Yoshihiko Kitada kazuhiro okamoto Takafumi Takei Xiufeng Jia Rui Chen Nobuo Yamaguchi Misao Tsubokawa Wen Hsin Wu Tsugiya Murayama Kenji Kawakita Deaprtment of Microbiology and Immunology Faculty of Pharmaceutical Sciences Hokuriku University Kanazawa Japan Deaprtment of Physiology Meiji University of Integrative Medicine Kyoto Japan. Department of Rehabilitation Kanazawa Medical University Uchinada-machi Japan Ishikawa Medicinal Products Research Center Kanazawa Japan Medical School College of Medicine Taipei Medical University Taiwan Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Two primary defense systems develop in vertebrates, innate and adaptive. Despite those defense systems, the overwhelming problems of possessing this dual system, the innate or adoptive do not seem to guard or even prevent the development of one internal threat to survival, moreover sometimes direct to autoimmunity accompanying hypersensitivity. Further, every individual exposes to the risk of immunodeficiency in daily life with both internal and external stimuli. In this report, we tried to report the suitable menu for regulating the immune system modulate and discuss 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 health promoting menus such as hot spring hydrotherapy, acupuncture & moxibustion, light walking, independent to the western medicine. In this report, we try to summarize the regulatory effect of hot spring hydrotherapy as our representative menu 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, emotional hormones, receptor positive lymphoid cells. The regulative effects were confirmed also by other menu than hydrotherapy, acupuncture, walking etc. However, just by the simple comparison between the group before and after the hydrotherapy, we cannot exhibit the real regulatory effect by each menu. So we tried to show the effect by trying to indicate the constitution/condition dependent manner. Because the effect was not uniformly to each individual but it was dependent on each condition/constitution before the start of the menu. This is the one of the main proposes of this report for summaries 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. T

关键词： Hot Spring Hydrotherapy Peripheral Leukocyte Leukocyte Subsets Ratio Adrenaline Dopamine β2-Adrenergic Receptor Flow-Cytometry Constitution CAM Therapeutic Menu

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The advantages of radical distribution control and independent dual frequency on etch/ash

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半导体技术 2004年第8期29卷 41-46页

作者： Tanaka Hideaki Kubota kazuhiro Shin okamoto Tokyo Electron Ltd. Tokyo Electron Ltd.Tokyo Electron Ltd.

The transition to 65 nm beyond and 300 mm wafers posed many challenges on etch depth and critical dimension (CD) uniformity within wafer. In this paper, we introduce a radical distribution con- trol (RDC) system for an excellent uniformity control. Etch depth and CD uniformity within wafer are well controlled by adding RDC function to SCCMTM. For increasing productivity, an all-in-one process, that is, etch/ash at the same chamber continuously is proposed here. By utilizing the advantage of inde- pendent dual frequency, a bias-controlled two-step ash “hybrid ash” is combined in the all-in-one process. Hybrid ash uses bias control and low pres- sure to minimize liner loss and the damage of low-k materials, which is targeting 65nm and beyond.

关键词：蚀刻分布控制独立双频 RDC SCCM

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Cetuximab and panitumumab in a patient with colon cancer and concomitant chronic skin disease:A potential beneficial effect on psoriasis vulgaris

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World Journal of Gastroenterology 2015年第12期21卷 3746-3749页

作者： Ken okamoto Hiromichi Maeda Takeo Shiga Mai Shiga Ken Dabanaka kazuhiro Hanazaki Michiya Kobayashi Department of Human Health and Medical Sciences Kochi Medical School Hospital Cancer Treatment Center Kochi Medical School Hospital Department of Dermatology Kochi Medical School Department of Surgery Kochi Medical School

Monoclonal antibodies against epidermal growth factor receptor(EGFR) are used in the treatment of advanced colorectal cancer. However, these agents can induce severe dermatological side effects that discourage their administration in patients with chronic dermatological disease. EGFR plays a key role in normal skin development and immunological function, and is expressed in various tissues and organs, although contrarily, it is overexpressed in psoriasis-related skin lesions. Thus, discussion is ongoing regarding the putative pathological role and therapeutic potential of this protein. We herein report on a patient with advanced colon cancer and concomitant long-standing psoriasis vulgaris who received antiEGFR antibody monotherapy as a third-line treatment for metastatic disease. One week after the initiation of treatment, the patient's skin lesions dramatically subsided and the improvement was sustained during therapy. Based on this case, we propose that anti-EGFR antibody therapy is not necessarily contraindicated in patients with psoriasis vulgaris. Moreover, the findings reaffirmed that EGFR is an important molecule in the pathology of psoriasis.

关键词： Psoriasis Cetuximab Panitumumab Epidermal growth f

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