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In Vivo Development of Fetal Pig Kidneys in Mature Monkeys under Clinically Approved Immunosuppressant Drugs

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Engineering 2022年第3期8卷 65-73页

作者： Tsuyoshi Takamura Kenji Matsui Naoto Matsumoto Yatsumu Saito Toshinari Fujimoto Susumu Tajiri Shuichiro Yamanaka Kei Matsumoto Akimitsu Kobayashi Izumi yamamoto Hiroshi Sasaki Haruyuki Hirayama Hitomi Matsunari Kazuaki Nakano Hiroshi Nagashima Akihiko Kiyoshi Takao Kuroda Makoto Inoue takeshi Miyawaki Takashi Yokoo Eiji Kobayashi Division of Nephrology and Hypertension Department of Internal MedicineThe Jikei University School of MedicineTokyo 105-8461Japan Department of Urology The Jikei University School of MedicineTokyo 105-8461Japan Department of Plastic and Reconstructive Surgery The Jikei University School of MedicineTokyo 105-8461Japan Meiji University International Institute for Bio-Resource Research Kanagawa 214-8571Japan Sumitomo Dainippon Pharma Co. Ltd.Osaka-fu 564-0053Japan Department of Kidney Regenerative Medicine The Jikei University School of MedicineTokyo 105-8461Japan

Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman ***,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney *** study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as *** left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the *** was performed with only US Food and Drug Administration-approved *** fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus ***,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular ***,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal *** immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.

关键词： Cynomolgus monkey Pig Kidney Fetal kidney Immunosuppression

Isolation of a Novel Lodging Resistance QTL Gene Involved in Strigolactone Signaling and Its Pyramiding with a QTL Gene Involved in Another Mechanism

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Molecular Plant 2015年第2期8卷 303-314页

作者： Kenji Yano Taiichiro Ookawa Koichiro Aya Yusuke Ochiai Tadashi Hirasawa takeshi Ebitani takeshi Takarada Masahiro Yano Toshio yamamoto Shuichi Fukuoka Jianzhong Wu Tsuyu Ando Reynante Lacsamana Ordonio Ko Hirano Makoto Matsuoka Bioscience and Biotechnology Center Nagoya University Nagoya Aichi 464-8601 Japan Graduate School of Agriculture Tokyo University of Agriculture and Technology Fuchu Tokyo 183-8509 Japan Agricultural Research Institute Toyama Agricultural Forestry & Fisheries Research Center Toyama 939-8153 Japan National Institute of Agrobiological Sciences Tsukuba Ibaraki 305-8602 Japan These authors contributed equally to this article.

Lodging has been a major roadblock to attaining increased crop productivity. In an attempt to understand the mechanism for culm strength in rice, we isolated an effective quantitative trait locus （QTL）, STRONG CULM3 （SCM3）, the causal gene of which is identical to rice TEOSINTE BRANCHED1 （OsTB1）, a gene previously reported to positively control strigolactone （SL） signaling. A near-isogenic line （NIL） carrying SCM3 showed enhanced culm strength and increased spikelet number despite the expected decrease in tiller number, indicating that SL also has a positive role in enhancing culm strength and spikelet number. We produced a pyramiding line carrying SCM3 and SCM2, another QTL encoding AP01 involved in panicle development. The NIL-SCM2＋SCM3 showed a much stronger culm than NIL-SCM2 and NIL-SCM3 and an increased spikelet number caused by the additive effect of these QTLs. We discuss the importance of utilizing suitable alleles of these STRONG CULM QTLs without inducing detrimental traits for breeding.

关键词： culm OsTB1 strigolactone lodging resistance quantitative trait loci

The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

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Asian Journal of Andrology 2009年第3期11卷 299-307页

作者： Kaori yamamoto-Ishikawa Hiroyoshi Suzuki Masahiko Nezu Naoto Kamiya Takashi Imamoto Akira Komiya Kazuyuki Sogawa takeshi Tomonaga Fumlo Nomur Tomohiko Ichikawa Department of Urology Graduate School of Medicine Chiba University Chiba 260-8670 Japan Department of Molecular Diagnosis Graduate School of Medicine Chiba University Chiba 260-8670 Japan

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients＇ sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points： point A, pre-treatment; point B, at the nadir of the prostate- specific antigen （PSA） level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients＇ sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I （ApoC-I）. Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-i protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

关键词： apolipoprotein C-I hormonal therapy prognosis prostate cancer surface-enhanced laser desorption/ionization time-offlight mass spectrometry

Remission of bronchial asthma after viral clearance in chronic hepatitis C

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World Journal of Gastroenterology 2005年第47期11卷 7545-7546页

作者： Norihiko yamamoto Kazumoto Murata takeshi Nakano The First Department of Internal Medicine Mie University School of MedicineTsuMieJapan

A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

关键词：支气管哮喘病毒感染丙型肝炎病毒病理机制

Commonalities and differences between Brassica and Arabidopsis self-incompatibility

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Horticulture Research 2014年第1期1卷 40-44页

作者： Masaya yamamoto takeshi Nishio Graduate School of Agricultural Science Tohoku UniversitySendai 981-8555Japan

In higher plants,the self-incompatibility mechanism is important for inhibition of self-fertilization and facilitation of *** Brassicaceae,the self-incompatibility response is mediated by allele-specific interaction of the stigma-localized S-locus receptor kinase(SRK)with the pollen coat-localized ligand(SCR/SP11).All self-incompatible Brassicaceae plants analyzed have been found to have the SRK and SCR/SP11 genes in the S-locus *** Arabidopsis thaliana is self-compatible,transformation with functional SRK-SCR genes from self-incompatible Arabidopsis species confers the self-incompatibility phenotype to *** allele-specific interaction between SRK and SCR activates the downstream signaling cascade of *** two-hybrid analysis with a kinase domain of SRK as bait and genetic analysis suggested several candidate components of self-incompatibility signaling in ***,*** genes orthologous to the identified genes for Brassica self-incompatibility signaling were evaluated by using a self-incompatible transgenic *** plant and these orthologous genes were found not to be involved in self-incompatibility signaling in the transgenic *** this review,we describe common and different aspects of S-locus genomic regions and self-incompatibility signaling between Brassica and Arabidopsis.

关键词： Arabidopsis interaction analysis

Cell sheet technology for regeneration of esophageal mucosa

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World Journal of Gastroenterology 2012年第37期18卷 5145-5150页

作者： Ryo Takagi Masayuki Yamato Nobuo Kanai Daisuke Murakami Makoto Kondo Takaaki Ishii takeshi Ohki Hideo Namiki Masakazu yamamoto Teruo Okano Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University Department of Surgery Institute of GastroenterologyTokyo Women's Medical University Graduate School of Science and Engineering Waseda University

The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells. Cell-and tissue-based therapies have been successfully applied to human patients, and several tissue-engineered products have been approved by the regulatory agencies and are commercially available. In the review article, we describe our experience of development and clinical application of cell sheet-based regenerative *** mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been shown to be useful for removal of gastrointestinal neoplasms with less invasiveness compared with open surgery, especially in esophageal surgery. However, postoperative inflammation and stenosis are major complications observed after intensive mucosal resection. Therefore, we have developed novel regenerative medicine to prevent such complications and promote wound healing of esophageal mucosa after EMR or ESD. Transplantable oral mucosal epithelial cell sheets were fabricated from patients' own oral mucosa. Immediately after EMR or ESD, fabricated autologous cell sheets were endoscopically transplanted to the ulcer sites. We performed a preclinical study with a canine model. In human clinical settings, cell culture and cell sheet fabrication were performed in clean rooms according to good manufacturing practice guidelines, and pharmaceutical drugs were used as supplements to culture medium in place of research regents used in animal study. We believe that cell-based regenerative medicine would be useful to improve quality of life of patients after EMR or ESD.

关键词：口腔黏膜食管癌再生技术电池板上皮细胞临床应用再生医学胃肠道肿瘤

ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture system

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International Journal of Oral Science 2018年第4期10卷 253-262页

作者： Masaharu Noi Ken-Ichi Mukaisho Saori Yoshida Shoko Murakami Shinya Koshinuma takeshi Adachi Yoshisato Machida Masashi Yamori Takahisa Nakayama Gaku yamamoto Hiroyuki Sugihara Department of Oral and Maxillofacial Surgery Shiga University of Medical Science Department of Pathology Division of Molecular Diagnostic PathologyShiga University of Medical Science Dental Oral Surgery Nagahama Red Cross Hospital

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase(ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbedwith a structure resembling the loose connective tissue morphology in a novel 3 D culture system. We confirmed that the 3 D system using CellbedTMaccurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3 D-cultured tongue cancer cell lines than in 2 D cultures. Typically, under conventional 2 D culture conditions, F-actin and cortactin are colocalized in the form of puncta within ***, in the 3 D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3 D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3 D culture systems using Cellbed? are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.

关键词： ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture sy HSC

Tracing founder haplotypes of Japanese apple varieties: application in genomic prediction and genome-wide association study

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Horticulture Research 2021年第1期8卷 614-627页

作者： Mai FMinamikawa Miyuki Kunihisa Koji Noshita Shigeki Moriya Kazuyuki Abe takeshi Hayashi Yuichi Katayose Toshimi Matsumoto Chikako Nishitani Shingo Terakami Toshiya yamamoto Hiroyoshi Iwata Laboratory of Biometry and Bioinformatics Department of Agricultural and Environmental BiologyGraduate School of Agricultural and Life SciencesThe University of Tokyo1-1-1 YayoiBunkyoTokyo 113-8657Japan Institute of Fruit Tree and Tea Science National Agriculture and Food Research Organization(NARO)2-1 FujimotoTsukubaIbaraki 305-8605Japan Division of Apple Research Institute of Fruit Tree and Tea ScienceNARO92-24 Shimokuriyagawa NabeyashikiMoriokaIwate 020-0123Japan Institute of Crop Science NARO2-1-2 KannondaiTsukubaIbaraki 305-8518Japan Institute of Agrobiological Sciences NARO1-2 OwashiTsukubaIbaraki 305-8634Japan

Haplotypes provide useful information for genomics-based approaches,genomic prediction,and genome-wide association *** a small number of superior founders have contributed largely to the breeding history of fruit trees,the information of founder haplotypes may be relevant for performing the genomics-based approaches in these *** this study,we proposed a method to estimate 14 haplotypes from 7 founders and automatically trace the haplotypes forward to apple parental(185 varieties)and breeding(659 F 1 individuals from 16 full-sib families)populations based on 11,786 single-nucleotide polymorphisms,by combining multiple ***,92%of the single-nucleotide polymorphisms information in the parental and breeding populations was characterized by the 14 founder *** use of founder haplotype information improved the accuracy of genomic prediction in 7 traits and the resolution of genome-wide association study in 13 out of 27 fruit quality traits analyzed in this *** also visualized the significant propagation of the founder haplotype with the largest genetic effect in genome-wide association study over the pedigree tree of the parental *** results suggest that the information of founder haplotypes can be useful for not only genetic improvement of fruit quality traits in apples but also for understanding the selection history of founder haplotypes in the breeding program of Japanese apple varieties.

关键词： breeding varieties prediction

Lateral pelvic lymph nodes for rectal cancer:A review of diagnosis and management

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1412-1424页

作者： Shimpei Ogawa Michio Itabashi Yuji Inoue takeshi Ohki Yoshiko Bamba Kurodo Koshino Ryosuke Nakagawa Kimitaka Tani Hisako Aihara Hiroka Kondo Shigeki Yamaguchi Masakazu yamamoto Department of Surgery Institute of GastroenterologyTokyo Women's Medical UniversityTokyo 162-8666Japan

The current status and future prospects for diagnosis and treatment of lateral pelvic lymph node(LPLN)metastasis of rectal cancer are described in this *** resonance imaging(MRI)is recommended for the diagnosis of LPLN metastasis.A LPLN-positive status on MRI is a strong risk factor for metastasis,and evaluation by MRI is important for deciding treatment *** dissection(LPLD)has an advantage of reducing recurrence in the lateral pelvis but also has a disadvantage of complications;therefore,LPLD may not be appropriate for cases that are less likely to have LPLN *** therapy(RT)and chemoradiation therapy(CRT)have limited effects in cases with suspected LPLN metastasis,but a combination of preoperative CRT and LPLD may improve the treatment ***,RT and CRT plus selective LPLD may be a rational strategy to omit unnecessary LPLD and produce a favorable treatment outcome.

关键词： Diagnosis Treatment Rectal cancer Lateral pelvic lymph node metastasis Lateral pelvic lymph node dissection Radiotherapy