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Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

World Journal of Gastroenterology 2006年第1期12卷 10-16页

作者： masanori ito Shinji Tanaka Tomoari Kamada Ken Haruma Kazuaki Chayama Department of Medicine and Molecular Science Hiroshima UniversityHiroshimaJapan Department of Endoscopy Hiroshima University HospitalHiroshimaJapan Gastroenterology Unit Department of Internal MedicineKawasaki Medical SchoolKurashikiJapan

Many epidemiological reports indicate that Helicobacter pylori （H pylori） infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/ intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without precancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non- randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

关键词： H pylori Eradication Gastritis Gastric neoplasm, Endoscopy

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Pronuclear microinjection is not suitable for RNA polymerase III promoter driven constitutive RNAi transgenesis in mice for XY male-to-female sex reversal by <i>Sry</i>gene knockdown

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Open Journal of Genetics 2012年第1期2卷 62-69页

作者： masanori ito Department of Pharmacology School of Medicine Faculty of Medicine Toho University 5-21-16 Omori-Nishi Otaku Tokyo 143-8540 Japan

Silencing of gene expression by RNA interference (RNAi) has become a widely used tool. For the study of mammalian gene function expression vectors for short hairpin RNA (shRNA) were developed. However the standard methods of shRNA transgenic (Tg) mice production have not been established. Sry (sex-determining region on the Y chromosome) is a mammalian sex-determining gene on the Y chromosome. In mice, the transient expression of Sry in supporting cell precursor cells between 10.5 and 12.5 days post-coitus (dpc) triggers the differentiation of Sertoli cells from granulosa cells. Then high efficiency of Sry gene silencing in Tg mice should induce XY male-to-female sex reversal. An shRNA Tg mouse targeting Sry gene was attempted to be generated by pronuclear microinjection. A low rate (Tg pups/all pups born after microinjection = 2/154 to 7/178) of Tg pups was observed. These Tg mice showed no XY male-to-female sex reversal. The results suggest that exogenous expression of small RNA might exert a negative effect on embryonic development and another approach should be needed for RNAi transgenesis in mice.

关键词： Transgenic Mice Pronuclear Microinjection RNA Interference

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Ubiquitous expression of Sry induces embryonic lethality related to suppression of Tie2/Tek expression

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Advances in Bioscience and Biotechnology 2010年第5期1卷 444-452页

作者： Kazuhisa Yoshida masanori ito Kou Yokouchi Kiyoshi Kano Kunihiko Naito Hideaki Tojo 不详

Sry (sex-determining region on the Y chromosome) is a mammalian sex-determining gene on the Y chromosome. In mice, the transient expression of Sry in supporting cell precursor cells between 10.5 and 12.5 days post-coitus (dpc) triggers the differentiation of Sertoli cells from granulosa cells. The importance of the strict regulation of Sry expression remains unknown. Thus, we attempted to produce a Sry ubiquitous-expressing transgenic (Tg) mouse in which foreign Sry is driven by the CAG (cytomegalovirus immediate-early enhancer, chicken beta-actin promoter, and the fusion intron of chicken beta-actin and rabbit beta-globin)-Sry gene for ubiquitous expressing Sry. A low rate (2/127) of Tg pups was observed, whereas the rate of early-stage transgenic embryos before birth was 19.2% (5/26). The Sry ubiquitous-expressing embryos showed abnormal development. The results suggest that ubiquitous expression of Sry exerts a negative effect on embryonic development. One of the two adult Tg mice showed low levels of Sry expression. The other Tg mouse showed high Sry transgene expression, but was mosaic for the transgene. Developmental analysis of transgenic F1 embryos produced from the mosaic Tg mouse revealed that ubiquitous expression of Sry had a lethal effect on embryonic development around 12.5 dpc. The histological data indicated that ubiquitous expression of Sry induced abnormal cardiovascular development, resulting in embryonic death. Enhanced expression of Sry suppressed endogenous Tie2/Tek (tyrosine kinase with Ig and EGF homology domains 2/tunica interna endothelial cell kinase) expression in Sry-transfected primary cultured cells from wild type embryonic hearts. The results indicate that the tissue-specific and stage-specific expression of Sry is essential for normal embryogenesis.

关键词： Sry Tie2/Tek Transgenic Mice

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Clinical and computed tomography findings of appendiceal diverticulitis vs acute appendicitis

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世界胃肠病学杂志：英文版 2015年第13期21卷 3921-3927页

作者： Daisuke ito Kenji Miki Shimizu Seiichiro Shojiro Hata Kaoru Kobayashi masanori Teruya Michio Kaminishi Department of Gastro- intestinal Surgery Showa General HospitalTokyo 187--8510Japan Department of Pathology Showa General HospitalTokyo 187-8510Japan

AIM: To study the clinical features and computed tomography(CT) findings of appendiceal diverticulitis vs acute ***: We retrospectively reviewed the records of 451 patients who had undergone appendectomy inour in stitution from January 2007 to September 2012. Patient demographics, clinical features, pathological findings, and surgical outcomes were analyzed. We also compared preoperative CT images of 25 patients with appendiceal diverticulitis with those of 25 patients with acute ***: Among 451 patients, 44(9.7%) were diagnosed to have appendiceal diverticulitis and 398(86.9%) to have acute appendicitis. Patients with appendiceal diverticulitis were older(59 vs 37 years, P < 0.001) and had a longer duration of the illness(4.0 d vs 1.0 d, P < 0.001). Perforation rates in patients with appendiceal diverticulitis were higher(68% vs 27%, P < 0.001). The appendix could be visualized in only 13 patients(52%) among the appendiceal diverticulitis cases, but in all acute appendicitis cases. CT findings suggestive of appendiceal diverticulitis included the absence of fluid collection in the appendix(84% vs 12%, P < 0.001), absence of appendicolith(92% vs 52%, P = 0.005), and formation of abscess(68% vs 16%, P < 0.001). Appendiceal diverticula were identified in 6 patients(24%).CONCLUSION: Among patients who had undergone appendectomy, 9.7% had appendiceal diverticulitis. Patients with appendiceal diverticulitis had different clinical features and CT findings from patients with acute appendicitis.

关键词： Appendiceal diverticulitis Acute appendicitis Comp

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Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro

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Open Journal of Immunology 2012年第4期2卷 149-160页

作者： Jun Tanaka Kumiko Hirano Yuzuru Sakamoto Akiko Sugahara-Tobinai Shota Endo Yumi ito-Matsuoka Atsushi Nakano masanori Inui Lars Nitschke Toshiyuki Takai Department of Experimental Immunology Institute of Development Aging and Cancer Tohoku University Sendai Japan Department of Genetics University of Erlangen Erlangen Germany Osaka Research Laboratory Benesis Corporation Osaka Japan

A therapeutic preparation of polyclonal human IgG, i.e., intravenous immunoglobulin (IVIg), has been employed to treat several inflammatory and autoimmune disorders. B cells are supposed to be a target of IVIg, but the molecular mechanism is elusive because of the lack of a suitable experimental system. To gain an insight into the beneficial effect of IVIg on B cells, we first established an experimental setting in which IVIg modulates a murine B cell function in vitro, and then aimed at identifying the mechanistic features at the molecular level. Here we show that IVIg down-regulates IL-10 production by CpG-activated B cells in vitro. The responsible component of IVIg was identified as the F(ab’)2 portion, whose polyclonality is mandatory for the suppressive effect. IVIg, bound to the surface of activated B cells, was found to be co-localized with intracellular SHP-1 on confocal laser microscopy, suggesting that B cell-surface immunoreceptor tyrosine-based inhibitory motif-harboring receptors that recruit SHP-1 are target molecules for IVIg in our experimental setting. Overall, we postulate a scenario in which IVIg attenuates B cells by suppressing IL-10 production, a B cell growth factor, and thus down-regulates the production of pathogenic antibodies.

关键词： F(ab’)2 Fragment Immune Inhibition ITIM Receptors Polyclonal IgG SHP-1

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Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin against Lung Cancer by Promoting Angiogenesis

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Advances in Lung Cancer 2017年第1期6卷 1-11页

作者： Yun-Mo Li Yasushi Ohno Norihiko Funaguchi Takenobu Gomyo Yuka Sasaki Sayaka Toyoshi Daizo Kaito Komei Yanase Junki Endo Fumitaka ito masanori Kawasaki Shinya Minatoguchi Department of Cardiology and Respirology Graduate School of Medicine Gifu University Gifu Japan Department of Respiratory Medicine Murakami Memorial Hospital Asahi University Mizuho Japan

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

关键词： Granulocyte Colony-Stimulating Factor Lung Cancer G-CSF Receptor Angiogenesis Anticancer Agent Cisplatin TNF-Alpha IL-12

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Integrated genome-wide differentiation and association analyses identify causal genes underlying breeding-selected grain quality traits in japonica rice

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Molecular Plant 2023年第9期16卷 1460-1477页

作者： Hideki Yoshida Satoshi Okada Fanmiao Wang Shohei Shiota Masaki Mori Mayuko Kawamura Xue Zhao Yiqiao Wang Naho Nishigaki Asako Kobayashi Kotaro Miura Shinya Yoshida Masaru Ikegami Akitoshi ito Lin-Tzu Huang Yue-le Caroline Hsing Yoshiyuki Yamagata Yoichi Morinaka masanori Yamasaki Toshihisa Kotake Eiji Yamamoto Jian Sun Ko Hirano Makoto Matsuoka Institute of Fermentation Sciences Fukushima UniversityFukushima 960-1248Japan Bioscience and Biotechnology Center Nagoya UniversityNagoyaAichi 464-8601Japan Food Resources Education and Research Center Graduate School of Agricultural ScienceKobe UniversityUzuranoKasaiHyogo 675-2103Japan Research Center of Genetic Resources NARO2-1-1 KannondaiTsukubaIbaraki 305-8602Japan Rice Research Institute Shenyang Agricultural UniversityShenyangChina Division of Life Science Graduate School of Science and EngineeringSaitama University255 Shimo-okuboSakura-kuSaitamaJapan Fukui Agricultural Experiment Station Fukui 918-8215Japan Department of Bioscience and Biotechnology Fukui Prefectural UniversityFukui 910-1195Japan Hyogo Prefectural Research Center for Agriculture Forestry and FisheriesKasaiHyogo 679-0198Japan Research Insttute for Food and Agriculture Ryukoku UniversityOotsuShiga 520-2194Japan Food Research Centre Aichi Centre for Industry and Science Technology2-1-1 Shimpukuji-choNagoyaAichi 451-0083Japan institute of Plant and Microbial Biology Academia SinicaTaipeiTaiwanChina Department of Agronomy National Taiwan UniversityTaipeiTaiwanChina lant Breeding Laboratory Facultyf gricultureKyushu University744MoookaNishikuFukukaJapan Graduate School of Agiculture Meji University1-1-1 Higashi-MitaTama-kuKawasakiKanagawa 214571Japa Crop Science Laboratory Faculty of AgricultureNigata UniversityIkarashiNishi-kuNigata 950-2181Japan

Improving grain quality is a primary objective in contemporary rice *** modern rice breeding has developed two different types of rice,eating and sake-brewing rice,with different grain characteristics,indicating the selection of variant gene alleles during the breeding *** the critical importance of promptly and efficiently identifying genes selected in past breeding for future molecular breeding,we conducted genome scans for divergence,genome-wide association studies,and map-based ***,we successfully identified two genes,OsMnS and OsWOX9D,both contributing to rice grain *** encodes a mannan synthase that increases the white core frequency in the endosperm,a desirable trait for sake brewing but decreases the grain appearance ***9D encodes a grass-specific homeobox-containing transcription factor,which enhances grain width for better sake ***,haplotype analysis revealed that their defective alleles were selected in East Asia,but not Europe,during modern *** addition,our analyses indicate that a reduction in grain mannan content during African rice domestication may also be caused a defective OsMnS allele due to breeding *** study not only reveals the delicate balance between grain appearance quality and nutrition in rice but also provides a new strategy for isolating causal genes underlying complex traits,based on the concept of“breeding-assisted genomics”in plants.

关键词： rice grain quality sake brewing mannan genomic analysis

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使用双时相绘图分析法进行PET神经受体探针的动力学特征视觉评估

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中华核医学与分子影像杂志 2017年第12期37卷 826-826页

作者：唐军 Hiroshi ito Yoko Ikoma Chie Seki Yasuyuki Kimura Hiroshi Kawaguchi Hiroyuki Takuwa Masanon Ichise Tetsuya Suhara Twao Kanno 上海交通大学附属苏州九龙医院核医学科 Department of Molecular Imaging and Theranostics National Institute of Radiological Sciences

目的在PET神经受体显像研究中,显像剂的动力学特征通过二室模型（2-TCM）来描述,包括总分布容积（V;）、不可置换的分布容积(V;)和结合能力(BP;)在内的结合参数可以通过模型的动力学参数分析来确定。结合参数估算的稳定性取决于放射性... 详细信息

目的在PET神经受体显像研究中,显像剂的动力学特征通过二室模型（2-TCM）来描述,包括总分布容积（V;）、不可置换的分布容积(V;)和结合能力(BP;)在内的结合参数可以通过模型的动力学参数分析来确定。结合参数估算的稳定性取决于放射性配体的动力学特征。为描述这些动力学特征,课题组在先前发表的论文中建立了一种双时相绘图分析法,该方法依据回归曲线早期相和延迟相在x轴上的截距来分别估算V;和V;。该研究中,课题组进一步用这种双时相绘图分析法对神经受体对应的放射性配体的动力学特征进行视觉评估,同时使用具有各个不同结合参数的模拟脑组织的时间活度曲线（TACs）进行二室模型的动力学分析,以研究双时相曲线的形状和参数估算的稳定性之间的关系。方法根据二室模型,在动脉输入函数和假设的动力学参数的基础上生成了90 min的TACs。随后对这些模拟的TACs进行双时相绘图分析,并对每个TAC曲线的曲率进行视觉评估。同时还生成了几种具有不同动力学参数的不同噪声水平的。TACs,计算每个TAC结合参数的变异和偏移,并比较这些变异、偏移与双时相曲线形状的关系。结果双时相绘图分析结果显示,TACs的曲率越高则特异性结合的水平越高、解离越慢,而解离慢的放射性配体其V;和BP;的四分位数间距越小。结论放射性配体曲线的曲率越大、解离越慢表明经动力学特征分析获得的结合参数V;和BP;越稳定。动力学特征分析方法应该被考虑用于放射性配体的动力学研究。

关键词： PET 绘图分析受体转运体

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