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| 1 | Human pluripotent stem cells:Towards therapeutic development for the treatment of lifestyle diseases显示文摘There are two types of human pluripotent stem cells: Embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs),both of which launched themselves on clinical trials after having taken measures to overcome problems: Blocking rejections by immunosuppressants regarding ESCs and minimizing the risk of tumorigenicity by depleting exogenous gene components regarding iP SCs.It is generally assumed that clinical applications of human pluripotent stem cells should be limited to those cases where there are no alternative measures for treatments because of the risk in transplanting those cells to living bodies.Regarding lifestyle diseases,we have already several therapeutic options,and thus,development of human pluripotent stem cell-based therapeutics tends to be avoided.Nevertheless,human pluripotent stem cells can contribute to the development of new therapeutics in this field.As we will show,there is a case where only a short-term presence of human pluripotent stem-derived cells can exert long-term therapeutic effects even after they are rejected.In those cases,immunologically rejections of ESC-or allogenic iP SC-derived cells may produce beneficial outcomes by nullifying the risk of tumorigenesis without deterioration of therapeutic effects.Another utility of human pluripotent stem cells is the provision of an innovative tool for drug discovery that are otherwise unavailable.For example,clinical specimens of human classical brown adipocytes(BAs),which has been attracting a great deal of attention as a new target of drug discovery for the treatment of metabolic disorders,are unobtainable from living individuals due to scarcity,fragility and ethical problems.However,BA can easily be produced from human pluripotent stem cells.In this review,we will contemplate potential contribution of human pluripotent stem cells to therapeutic development for lifestyle diseases. | Miwako Nishio Masako Nakahara Akira Yuo Kumiko Saeki | 2016 | World Journal of Stem Cells2016，8，2： | 2 |
| 2 | Preadministration of flurbiprofen suppresses prostaglandin production and postoperative pain in orthopedic patients undergoing tourniquet inflation显示文摘 | Masafumi Takada Makoto Fukusaki Yoshiaki Terao Kazunori Yamashita Chiaki Inadomi Miwako Takada Koji Sumikawa | 2007 | Journal of Clinical Anesthesia2007，，2： | 2 |
| 3 | FDG-PET is effective in the detection of granulocytic sarcoma in patients with myeloid malignancy显示文摘 | Koki Ueda Motoshi Ichikawa Miwako Takahashi Toshimitsu Momose Kuni Ohtomo Mineo Kurokawa | 2010 | Leukemia Research2010，，9： | 1 |
| 4 | Fund size and the syndication of venture capital investments显示文摘 | Miwako Nitani Allan Riding* | 2013 | Venture Capital2013，，1： | 1 |
| 5 | Optimal Frequency Hopping Sequences: A- Combinatorial Approach 显示文摘 | Ryoh Fuji - Ham Ying Miao Miwako Mishima | 2004 | IEEE Transactions on Information Theory2004，50，10： | 1 |
| 6 | Enhancement of anticterial effects of epigallocatechin gallate, using ascorblc acid显示文摘 | Tsutomu Hatano Mayumi Tsugawa Miwako Kusuda | 2008 | Phytochemistry2008，，31： | 1 |
| 7 | Rapid caterorization of pathogenic Escherichia coli by multiplex PCR 显示文摘 | Keiko K Tomoko S Miwako S | 2005 | Microbiol lmmunol2005，49，6： | 1 |
| 8 | Thermal expansion of La1–xCaxCrO3 显示文摘 | HIDEKO H MIEKO W MIWAKO O | 2001 | Solid State Ionics2001，144，34： | 1 |
| 9 | In-hospital and one-year outcomes for patients undergoing percutaneous coronary intervention for acute myocardial infarction显示文摘 | Miwako Shihara Hiroyuki Tsutsui Miyuki Tsuchihashi Hideo Tada Suminori Kono Akira Takeshita | 2002 | The American Journal of Cardiology2002，，9： | 1 |
| 10 | Immunohistologic study on the expressions of [alpha ]-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma显示文摘 | Miwako Fujioka Yutaka Nakashima Osamu Nakashima Masamichi Kojiro | 2001 | Hepatology2001，，6： | 1 |
| 11 | Higher preoperative D - dimer value remain high postoperatively in patients with rheumatoid arthritis compared with those with osteoarthrosis 显示文摘 | Yukiko M Miwako K | 2006 | J Anesth2006，20，： | 1 |
| 12 | Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: Changes during 1-year antihypertensive therapy with angiotensin-converting enzyme inhibitor显示文摘 | Masakazu Kohno Takeshi Horio Koji Yokokawa Kenichi Yasunari Miwako Ikeda Mieko Minami Naotsugu Kurihara Tadanao Takeda | 1995 | The American Journal of Medicine1995，，3： | 1 |
| 13 | Modification of nitriteproduction and phagocytosis of thioglycollate-elicited mouse perito-neal macrophages by Bovine Casein Digests 显示文摘 | HAJIME OTANI MIWAKO FUTAKAMI | 1996 | Food & AgriculturalImmunology1996，，： | 1 |
| 14 | New categorization of human vascular endothelial cells by pro-vs anti-proliferative phenotypes显示文摘AIM: To integrally understand the effects of human vascular endothelial cells(VECs) on the proliferation of vascular smooth muscle cells(VSMCs).METHODS: Various kinds of human VECs of different origins were co-cultured with human aortic smooth muscle cells, a representative of human VSMCs. To exclude the irrelevant effects due to growth competition between VECs and VSMCs, the proliferation of VECs had previously been arrested via a low-dose gamma rayirradiation. To discriminately analyze the proliferation of VSMCs from that of VECs, the former cells were labeled with red fluorescent dye while the latter cells were labeled with green fluorescent dye before performing coculture experiments. After 4 d, total cells were harvested and subjected to flow cytometric analyses. Decrements in red fluorescence intensities due to proliferationmediated dilutions were measured and mathematically processed using a specific software to quantitatively evaluate the proliferation of VSMCs. The findings obtained from the flow cytometry-based analyses were further validated by microscopic observations. RESULTS: Commercially available primary cultured human VECs exclusively promoted VSMC proliferation regardless of their tissue origins and we termed these pro-proliferative VECs as 'typeⅠ'. By contrast, VECs freshly generated from human bone marrow-derived endothelial progenitors cells or human pluripotent stem cells including embryonic stem cells and induced pluripotent stem cells suppressed VSMC proliferation and we termed these anti-proliferative VECs as 'typeⅡ'. Repetitive subcultures as well as oxidative stress induced 'type Ⅱ VECs to typeⅠ' conversion along with an induction of Regulator of G-protein signaling 5(RGS5)Compatibly, anti-oxidant treatments suppressed both the subculture-dependent 'typeⅡ to typeⅠ' conversion and an induction of RGS5 gene. Immunostaining studies of clinical specimens indicated that RGS5 protein expressions in endothelial layers were low in norma arteries but they were up-regulated in pathologica arteries including hypertension, atherosclerosis and autoimmune vasculitis in a dose-dependent manner Overexpression and knockdown of RGS5 caused that'typeⅡ to typeⅠ' and 'typeⅠ to type Ⅱ' phenotype conversions of VECs, respectively. CONCLUSION: Human VECs are categorized into two types: pro-proliferative RGS5^(high) VECs(typeⅠ) and antiproliferative RGS5 ^(low) VECs(typeⅡ). | Miwako Nishio Masako Nakahara Chikako Sato Koichi Saeki Hidenori Akutsu Akihiro Umezawa Kazuyuki Tobe Kazuki Yasuda Akira Yuo Kumiko Saeki | 2015 | World Journal of Translational Medicine2015，4，3： | 1 |
| 15 | p38 mitogen-activated protein kinase regulates type-Ⅰ vs type-Ⅱ phenotyping of human vascular endothelial cells显示文摘AIM: To identify kinases involved in phenotype regulation of vascular endothelial cells(VECs): Proproliferative G-protein signaling 5(RGS5)^(high)(typeⅠ) vs anti-proliferative RGS5^(low)(typeⅡ) VECs.METHODS: Proteomic kinase assays were performed to identify the crucial kinase involved in the phenotype regulation of human VECs using typeⅠ VECs, which promotes the proliferation of human vascular smooth muscle cells(VSMCs), and typeⅡ VECs, which suppress the proliferation of human VSMCs. The assays were performed using multiple pairs of typeⅠ and typeⅡ VECs to obtain the least number of candidates. The involvement of the candidate kinases was verified by evaluating the effects of their specific inhibitors on the phenotype regulation of human VECs as well as the expression levels of regulator of RGS5, which is the causative gene for the 'typeⅡ to typeⅠ' phenotype conversion of human VECs. RESULTS: p38α mitogen-activated protein kinase(p38α MAPK) was the only kinase that showed distinctive activities between typeⅠ and typeⅡ VECs: p38α MAPK activities were low and high in type-Ⅰand typeⅡ VECs, respectively. We found that an enforced expression of RGS5 indeed lowered p38α MAPK activitiesin typeⅡ VECs. Furthermore, treatments with a p38α MAPK inhibitor nullified the anti-proliferative potential in typeⅡ VECs. Interestingly, MAPK inhibitor treatments enhanced the induction of RGS5 gene. Thus, there is a vicious cycle between 'RGS5 induction' and 'p38α MAPK inhibition', which can explain the unidirectional process in the stress-induced 'typeⅡ to typeⅠ' conversions of human VECs. To understand the upstream signaling of RGS5, which is known as an inhibitory molecule against the G protein-coupled receptor(GPCR)-mediated signaling, we examined the effects of RGS5 overexpression on the signaling events from sphingosine-1-phosphate(S1P) to N-cadherin, because S1 P receptors belong to the GPCR family gene and N-cadherin, one of their downstream effectors, is reportedly involved in the regulation of VEC-VSMC interactions. We found that RGS5 specifically bound with S1P1. Moreover, N-cadherin localization at intercellular junctions in typeⅡ VECs was abolished by 'RGS5 overexpression' and 'p38α MAPK inhibition'.CONCLUSION: p38α MAPK plays crucial roles in 'type-Ⅰ vs type-Ⅱ' phenotype regulations of human VECs at the downstream of RGS5. | Masako Nakahara Miwako Nishio Koichi Saeki Akira Yuo Kumiko Saeki | 2015 | World Journal of Translational Medicine2015，4，3： | 1 |
| 16 | Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus 显示文摘 | Tsutomu H Miwako K Kazutoshi I | 2005 | Phytochemistry2005，66，17： | 1 |
| 17 | Pro-vs anti-stenotic capacities of type-Ⅰ vs type-Ⅱ human induced pluripotent-derived endothelial cells显示文摘AIM:To verify in vivo relevance of the categorization of human vascular endothelial cells(VECs)into type-I(proproliferative)and type-II(anti-proliferative).METHODS:Endothelial layers of murine femoral arteries were removed by wire injury(WI)operation,a common technique to induce arteriostenosis.Type-I and type-II VECs produced from human induced pluripotent stem cells(iPSCs),whose characters were previously determined by their effects on the proliferation of vascular smooth muscle cells in in vitro co-culture experiments,were mixed with Matrigel?Matrix.The mixtures were injected into subcutaneous spaces around WI-operated femoral arteries for the transplanted human iPSC-derived VECs(iPSdECs)to take a route to the luminal surface via vasa vasorum,a nutrient microvessel for larger arteries.Histologies of the femoral arteries were examined over time.The presence of human iPSdECs was checked by immunostaining studies using an antibody that specifically recognizes human VECs.Degrees of stenosis of the femoral arteries were calculated after three weeks.To determine the optimal experimental condition,xenotransplantation experiments were performed under various conditions using immunocompromised mice as well as immunocompetent mice with or without administration of immunosuppressants.RESULTS:Because immunocompromised mice showed unexpected resistance to WI-induced arteriostenosis,we performed xenotransplantation experiments using immunocompetent mice along with immunosuppressant administrations.After one week,luminal surfaces of the WI-operated arteries were completely covered by human iPSdECs,showing the efficacy of our novel transplantation technique.After three weeks,type-IiPSdECs-transplanted arteries underwent total stenosis,while type-II-iPSdECs-transplanted arteries remained intact.However,untransplanted arteries of immunosuppressant-treated mice also remained intact by unknown reasons.We found that transplanted human VECs had already been replaced by murine endothelial cells by this time,indicating that a transient existence of human type-II-iPSdECs on arterial luminal surfaces can sufficiently prevent the development of stenosis.Thus,we re-performed xenotransplantation experiments using immunocompetent mice without administrating immunosuppressants and found that arteriostenosis was accelerated or prevented by transplantation of type-I or type-II iPSdECs,respectively.Similar results were obtained from the experiments using human embryonic stem cell-derived VECs at early passages(i.e.,type-II)and late passages(i.e.,type-I).CONCLUSION:Pro-and anti-stenosis capacities of type-I and type-II human iPSdECs were verified,respectively,promising a therapeutic application of allogenic iPSdECs. | Miwako Nishio Masako Nakahara Koichi Saeki Katsuhito Fujiu Hiroshi Iwata Ichiro Manabe Akira Yuo Kumiko Saeki | 2015 | World Journal of Translational Medicine2015，4，3： | 1 |
| 18 | Optimal frequency-hopping sequence: a combinatorial approach显示文摘 | Ryoh Fuji-Hara Ying Miao Miwako Mishima | 2004 | IEEE Info Theory2004，50，： | 1 |
| 19 | Clinicopathological study of pheochromocytoma of the urinary bladder:Immunohistochemical,flow cytometric and ultrastructural findings with review of the literature显示文摘 | Kato Hiroyuk Suzuki Masafumi Mukai Miwako | 1999 | Pathology International1999，49，12： | 1 |
| 20 | Factors affecting breast cancer screening behavior in Japan-Assessment u- sing the health belief model and conjoint analysis显示文摘 | Miwako T Hiromi K Yuko M | 2013 | Asi- an Pac J Cancer Prev2013，14，24： | 1 |
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