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Open Journal of Psychiatry 2017年第4期7卷 329-343页

作者： takashi hirata Takuji Uemura Manabu Shinohara Masami Hirano Department of Neuropsychiatry and Clinical Ethics Interdisciplinary Graduate School of Medicine University of Yamanashi Yamanashi Japan Health Care Center University of Yamanashi Yamanashi Japan Kyosai Hospital Yamanashi Japan

Objectives: Dyshomeostasis of the dopaminergic system is implicated in the pathophysiology of eating disorders (EDs). We have previously reported an association between 3'-UTR VNTR (three prime untranslated region variable number of tandem repeat) of the Dopamine Transporter 1 (DAT1) gene and ED with binge eating behavior (EDBEB). Here we investigated whether variants in the coding region of the DAT1 gene also associate with EDBEB. Methods: The coding region and exon-intron junctions of the DAT1 gene were screened by direct sequencing using genomic DNA from EDBEB patients (n = 90) and healthy subjects (n = 114) on whom 3'-UTR VNTR variants had been previously determined. Results: rs2270912 and rs28363130, two of five known polymorphisms found by this screen, were significantly associated with EDBEB patients by genotype (p = 0.003, p = 0.011, respectively) and allele (p = 0.003, p = 0.012, respectively) frequency compared with healthy subjects. Interestingly, these polymorphisms associate with the risk 3'-UTR VNTR variant of EDBEB. Conclusion: Although our sample size was small, we show here that rs2270912 and rs28363130 associates with EDBEB and might act with 3'-UTR VNTR as a haplotype. These findings support the notion that the DAT1 gene plays a key role in the dopaminergic system of EDBEB.

关键词： Eating Disorder Binge Eating Behavior DAT1 Association Study Polymorphism

Recent Advances in Researches on Physiologically Active Substances in Holothurians

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Journal of Ocean University of China 2005年第3期4卷 193-197页

作者： hirata takashi Zaima Nobuhiro Yamashita Kyoko Noguchi Ryoko XUE Changhu Sugawara Tatsuya Graduate School of Agriculture Kyoto University Kyoto 606-8502 Japan Graduate School of Fisheries Sciences Hokkaido University Hakodate 041-8611 Japan College of Food Science and Engineering Ocean University of China Qingdao 266003 P. R. China

In this report, we reviewed recent literature on physiologically active substances from sea cucumbers (SCs) andtheir activities together with results obtained from our study. Preventive properties against lipid metabolism were reported inrats using a whole SC preparation with no particular constituent specified. Administration of the preparation lowered serumand hepatic cholesterol levels and improved the HDL/LDL ratio. These functions may be attributed to the stimulatory effectof the extract on the secretion of cholesterol in feces. Novel fucosylated chondroitin sulfates (FCSs) from Ludwigothureagrisea significantly induced fibroblast growth factor 2-dependent angiogenesis in human umbilical vein endothelial cells (HU-VECs). The proangiogenetic activity seemed attributable to the action of the sulfated fucose branches on the *** contain mycosporine-like amino acids (MAAs) that are capable of absorbing UV. A biogenetic precursor of MAAs wasfirst reported in SCs. The anti-proliferative effects of a branched chain fatty acid from a sea cucumber on prostate cancercells was reported with the activity of 5-lipoxygenase. Glycosphingolipid constituents in SCs have been systematically ana-lyzed over the past ten years. The results showed that the gangliosides in several SCs differed from those of mammals in thata sialic acid of SC gangliosides directly binded to glucose of cerebroside. Neuritogenic activity of the glycosphingolipids wasdemonstrated in vitro experiments and may lead to the development of therapeutic products for neurological disorders. Ourstudy also showed that sphingoid bases, the hydrolyzed products of glycosphingolipids from SCs, induced significant apoptosisin several tumor cell lines.

关键词：海参神经鞘脂类胆固醇物理活性物质保健功能营养价值海产动物

Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer

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World Journal of Gastroenterology 2012年第45期18卷 6577-6586页

作者： Yasutaka Sukawa Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Kunimoto Hiromu Suzuki Yasushi Adachi Mayumi Nakazawa Takayuki Nobuoka Mariko Kawayama Masashi Mikami takashi Matsuno Tadashi Hasegawa Koichi hirata Kohzoh Imai Yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University School of MedicineSapporo 60-8543Japan Department of Molecular Biology Sapporo Medical University School of MedicineSapporo 60-8543Japan First Department of Surgery Sapporo Medical University School of MedicineSapporo 60-8543Japan Department of Gastroenterology JR Sapporo HospitalSapporo 60-8543Japan Department of Surgery Sapporo Gekakinen HospitalSapporo 60-8543Japan Department of Surgical Pathology Sapporo Medical University HospitalSapporo 60-8543Japan Division of Cancer Research The Institute of Medical ScienceThe University of TokyoTokyo 108-8639Japan

AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling ***:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical *** patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical *** of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM *** criteria for HER2 positivity(0,1+,2+,and 3+) were *** that scored 3+ were considered *** of phospho Akt(pAkt) was also analyzed by *** were considered pAkt-positive when the percentage of positive tumor cells was 10% or ***3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by ***-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA *** instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and ***:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,***2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 *** in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,*** new types of PIK3CA mutation,R88Q and R108H,were found in *** PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in *** cancers(8%) were EBV-positive and this positivity significantly correlated with a diffu

关键词：表皮生长因子受体磷脂酰肌醇 Epstein-Barr病毒胃癌信号通路激酶突变频率微卫星不稳定性

Histopathological and genetic differences between polypoid and non-polypoid submucosal colorectal carcinoma

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World Journal of Gastroenterology 2007年第14期13卷 2048-2052页

作者： Ichiro hirata Fang-Yu Wang Mitsuyuki Murano Takuya Inoue Ken Toshina takashi Nishikawa Kentaro Maemura Department of Gastroenterology Fujita Health University Japan Department of Gastroenterology Jinling Hospital Nanjing University School of Medicine Nanjing 210000 Jiangshu Province China Second Department of Internal medicine Osaka medical College Japan Department of Anatomy Osaka Medical College Japan

瞄准：调查水虫息似的生长(PG ) 和非水虫息似的生长(NPG ) 之间的组织病理学说、基因的差别粘膜下层的侵略肤色表面的癌(CRC ) 。方法：粘膜下层 CRC 的 96 个案例的一个总数根据他们的生长类型被划分成二个组；PG 的 60 个案例和 NPG ... 详细信息

瞄准：调查水虫息似的生长(PG ) 和非水虫息似的生长(NPG ) 之间的组织病理学说、基因的差别粘膜下层的侵略肤色表面的癌(CRC ) 。方法：粘膜下层 CRC 的 96 个案例的一个总数根据他们的生长类型被划分成二个组；PG 的 60 个案例和 NPG 的 36 个案例。尺寸，发育异常的组织学的度，粘膜下层侵略的深度和淋巴节点转移在二个组之间被比较。而且， p53 的表示被免疫检测组织化学的染色，并且 K 地岬基因变化被聚合酶链反应检验基于的单个海滨的符合构造多型性(SSCP ) 。结果：在 NPG 组的损害的平均尺寸是比在 PG 组的那些显著地小的(7.5 公里对 13.8 公里， P < 0.001 ) 。当粘膜下层的巨大的侵略和淋巴节点转移的发生比在 PG 组在 NPG 类型更高显著地是两个时，发育异常的组织学的度趋于在 NPG 组更严重(64.3% 对 43.3% ， P = 0.004；43% 对 7% ， P = 0.008，分别地) 。另外， K 地岬基因变化在 NPG 组在 PG 组，而是没有在 67% 损害被检测，当在组织化学的表示在二之间被发现的 p53 免疫的差别都不组织时。结论：与 PG 粘膜下层的 CRC 相比， NPG 类型表明更经常的粘膜下层的巨大的侵略，更多的淋巴节点转移和更高的度发育异常。遗传上， NPG 类型显示出更不经常的 K 地岬变化。

关键词：突出膨大型非突出膨大粘膜下结肠直肠癌组织病理遗传差异

Pleckstrin homology domain of PRIP Inhibits exocytosis in PC12 cells by binding to phosphatidylinosltol 4,5 bisphosphate

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Pleckstrin homology domain of PRIP Inhibits exocytosis in PC...

Comparison of Efficacy and Safety Evaluation of Latanoprost Formulations with and without Benzalkonium Chloride

21st IUBMB and 12th FAOBMB International Congress of Biochemistry and Molecular Biology

作者： Jing Gao Hiroshi Takeuchi Zhao Zhang takashi Kanematsu Masato hirata Lab of Mol and Cell Biochem Fac of Dent SciKyushu Univ

＜正＞PRIP（Phospholipase C-related but catalytically inactive protein） was first identified as a novel Ins（1,4,5）Ps binding *** have recently found that the secretion of various peptide-hormones from multiple orga...

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Pharmacology & Pharmacy 2013年第4期4卷 377-384页

作者： Hiroyoshi Kasai Yumiko Aoyama takashi Kurasawa Tomoyo Imamura Kazuhiro Tsuruma Hideaki Hara Haruhisa hirata Tetsuya Yamamoto Department of Ophthalmology Gifu University Graduate School of Medicine Gifu Japan Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu Japan Research and Development Wakamoto Pharmaceutical Co. Ltd. Tokyo Japan Sagami Research Laboratories Wakamoto Pharmaceutical Co. Ltd. Kanagawa Japan

Background: This study investigated the safety (cytotoxicity in vitro) and pharmacological effects (ocular hypotensive effects and aqueous humor concentrations in normotensive monkeys in vivo) of latanoprost formulations with benzalkonium chloride (latanoprost with BAK) and without BAK (NP). Methods: A bioequivalence study of latanoprost with BAK and NP was also conducted on human healthy volunteers. Cytotoxicity and the protective effect against H2O2 stress in vitro were evaluated using human corneal epithelial cells. The ocular hypotensive effects in normotensive monkeys were measured by pneumatonometer and the aqueous humor concentrations of latanoprost free acid were determined by liquid chromatography/mass spectrum (LC/MS) methods. The bioequivalence study of latanoprost with BAK and NP was carried out as a single eye drop, two-sequence, crossover randomized study. Results: Cytotoxicity tests in vitro revealed that NP was less toxic than latanoprost with BAK and significantly inhibited H2O2 induced cell damage while latanoprost with BAK did not. The hypotensive efficacy and the latanoprost free acid concentrations in aqueous humor of each formulation were not significantly different in monkeys. In the bioequivalence study, NP was bioequivalent to latanoprost with BAK. NP was safer than latanoprost with BAK with respect the results obtained in the in vitro cytotoxicity test. There was no difference observed between latanoprost with BAK and NP in the IOP lowering effect in monkeys and healthy volunteers. Conclusion: Taken together, these results indicate that NP is as effective as latanoprost with BAK, and is more likely to maintain ocular surface health than latanoprost with BAK.

关键词： Latanoprost NP Benzalkonium Benzalkonium-Free Bioequivalence

Usefulness of fecal lactoferrin and hemoglobin in diagnosis of colorectal diseases

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World Journal of Gastroenterology 2007年第10期13卷 1569-1574页

作者： Ichiro hirata Masahiro Hoshimoto Osamu Saito Masanobu Kayazawa takashi Nishikawa Mitsuyuki Murano Ken Toshina Fang-Yu Wang Ryoichi Matsuse Department of Gastroenterology Fujita Health University Japan SecondDepartment of Internal Medicine Osaka Medical College Japan Department of Gastroenterology Jinling Hospital Nanjing University School of Medicine China Kyoto Medical Science Laboratory Japan

AIM:To evaluate prospectively usefulness of fecal lactoferrin(Lf)and fecal hemoglobin(Hb)in the diagnosis of colorectal ***:Fecal Lf and Hb were measured using ELISA in 872 patients before they underwent colorectal ***:Lf was positive in 18(50%)of 36 patients with colorectal cancer,25(15.9%)of 157 with colorectal polyps,29(46.8%)of 62 with ulcerative colitis,and 25(62.5%)of 40(62.5%)with Crohn's *** Hb-positive rates were 50%,12.1%,41.9% and 32.5%,*** the 318 patients free of abnormalities by colorectal endoscopy,Lf was positive in 29(9.1%)and Hb was positive in 15(4.7%).Among patients with Crohn's disease,the Lf-positive rate was significantly higher than the Hb-positive *** either high Lf or Hb levels were considered positive,the positive rates rose to 61.1%,51.6%,and 67.5% in the colorectal cancer group,ulcerative colitis group,and Crohn's disease group,*** both high Lf and Hb levels were rated positive,the positive predictive values(PPV)were 21% for colorectal cancer,33% for ulcerative colitis,and 17% for Crohn's disease,and PPV of high Hb level alone was 18%,25% and 13%,***:Fecal Lf and Hb were found useful in the detection of colorectal diseases,and the combination of the two measurements appears to increase the sensitivity and efficacy of diagnosis.

关键词：结肠直肠疾病诊断粪便乳铁传递蛋白粪便血红蛋白粪便检验临床价值

Incidental Uptake of In-111 Ibritumomab Tiuxetan in Surgically Treated Fracture

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Advances in Molecular Imaging 2011年第1期1卷 12-15页

作者： Hidenari hirata Makoto Nakagawa Koichiro Abe takashi Okafuji Kenji Shinozaki Ilseung Choi Naokuni Uike Shuji Sakai Department of Clinical Radiology Graduate School of Medical Sciences Kyushu University Department of Hematology National Kyushu Cancer Center Fukuoka Japan Department of Radiology National Kyushu Cancer Center Fukuoka Japan

In-111 ibritumomab tiuxetan pretherapy imaging is performed prior to radioimmunotherapy with Y-90 ibritumomab tiuxetan in patients with lymphoma in order to estimate the biodistribution of the radiolabeled antibodies. We report the case of a 61-year-old woman with relapsed follicular lymphoma. In-111 ibritumomab tiuxetan pretherapy imaging showed tracer accumulation in a surgically treated fracture of the left calcaneus as well as in the involved lesions. The patient had fractured her left calcaneus 6 months before the radioimmunotherapy, and fracture of the left calcaneus without lymphoma involvement had been revealed operatively at that time. Clinical features and magnetic resonance imaging (MRI) indicated an inflammatory response in the left heel. We concluded that this inflammation played an important role in the uptake on pretherapy imaging. It should be kept in mind that the inflammation is a differential diagnosis of lymphoma involvement in In-111 ibritumomab tiuxetan pretherapy imaging. To the best of our knowledge, this is the first case report of In-111 ibritumomab tiuxetan uptake in a surgically treated fracture.

关键词： In-111 Ibritumomab Fracture Lymphoma

Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis

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World Journal of Gastroenterology 2007年第11期13卷 1666-1671页

作者： Ichiro hirata Shingo Yasumoto Ken Toshina Takuya Inoue takashi Nishikawa Naoko Murano Mitsuyuki Murano Fang-Yu Wang Ken-ichi Katsu Department of Gastroenterology Fujita Health University Jaoan Second Department of Internal Medicine Osaka Medical College Japan Department of Gastroenterology Jinling Hospital Nanjing University School of Medicine Nanjing 210002 Jiangsu Province China

AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupⅠ(low-dose group), and DSS+PDTC-treated groupⅡ (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured. RESULTS: The DSS+PDTC-treated groupⅡ exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC- treated groupⅡ. CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis.

关键词：四氢吡咯二硫代氨基甲酸酯 PDTC 右旋糖苷硫酸钠盐诱发大肠炎炎症抑制作用评价

Targeting tight junctions during epithelial to mesenchymal transition in human pancreatic cancer

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World Journal of Gastroenterology 2014年第31期20卷 10813-10824页

作者： Daisuke Kyuno Hiroshi Yamaguchi Tatsuya Ito Tsuyoshi Kono Yasutoshi Kimura Masafumi Imamura Takumi Konno Koichi hirata Norimasa Sawada takashi Kojima Department of Surgery Sapporo Medical University School of Medicine Department of Cell Science Research Institute for Frontier Medicine Sapporo Medical University School of Medicine Department of Pathology Sapporo Medical University School of Medicine

Pancreatic cancer continues to be a leading cause of cancer-related death worldwide and there is an urgent need to develop novel diagnostic and therapeutic strategies to reduce the mortality of patients with this disease. In pancreatic cancer, some tight junction proteins, including claudins, are abnormally regulated and therefore are promising molecular targets for diagnosis, prognosis and therapy. Claudin-4 and-18 are overexpressed in human pancreatic cancer and its precursor lesions. Claudin-4 is a high affinity receptor of Clostridium perfringens enterotoxin(CPE). The cytotoxic effects of CPE and monoclonal antibodies against claudin-4 are useful as novel therapeutic tools for pancreatic cancer. Claudin-18 could be a putative marker and therapeutic target with prognostic implications for patients with pancreatic cancer. Claudin-1,-7, tricellulin and marvelD3 are involved in epithelial to mesenchymal transition(EMT) of pancreatic cancer cells and thus might be useful as biomarkers during disease. Protein kinase C is closely related to EMT of pancreatic cancer and regulates tight junctions of normal human pancreatic duct epithelial cells and the cancer cells. This review focuses on the regulation of tight junctions via protein kinase C during EMT in human pancreatic cancer for the purpose of developing new diagnostic and therapeutic modalities for pancreatic cancer.

关键词： Tight junctions Claudins Tricellulin MarvelD3 Norm