683 results on '"Takeshi Azuma"'
Search Results
202. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation
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T Fujita, Masaru Yoshida, Kazuyuki Kobayashi, Shin Nishiumi, Shinwa Tanaka, Masayuki Nishida, A Masuda, Yoshiyuki Mizushina, Hiromu Kutsumi, Takeshi Azuma, Shigeto Mizuno, and Yoshinori Morita
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Lipopolysaccharides ,Male ,Vitamin ,ARDS ,Necrosis ,Neutrophils ,Acute Lung Injury ,Immunology ,Drug Evaluation, Preclinical ,Inflammation ,Lung injury ,Kidney ,Mice ,chemistry.chemical_compound ,Menadione ,medicine ,Animals ,Humans ,Immunology and Allergy ,Lung ,Cells, Cultured ,Tumor Necrosis Factor-alpha ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Vitamin K2 ,NF-kappa B ,Vitamin K 3 ,Vitamin K 2 ,Vitamin K 1 ,medicine.disease ,Mice, Inbred C57BL ,Gene Expression Regulation ,chemistry ,Macrophages, Peritoneal ,Animal Studies ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Bronchoalveolar Lavage Fluid - Abstract
Summary Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.
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- 2009
203. Diverse Characteristics of the cagA Gene of Helicobacter pylori Strains Collected from Patients from Southern Vietnam with Gastric Cancer and Peptic Ulcer
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Masaru Yoshida, Bui Xuan Truong, Dao Van Long, Hoang Hoa Hai, Vo Thi Chi Mai, Tran Minh Thong, Keisuke Furumatsu, Takeshi Azuma, Hiroshi Tanaka, Hiromu Kutsumi, and Le Thanh Ly
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Adult ,Male ,Microbiology (medical) ,Peptic Ulcer ,medicine.medical_specialty ,Sequence analysis ,Molecular Sequence Data ,Virulence ,Biology ,digestive system ,Gastroenterology ,Helicobacter Infections ,Bacterial Proteins ,Stomach Neoplasms ,Internal medicine ,Genotype ,medicine ,Humans ,CagA ,Amino Acid Sequence ,Stomach cancer ,Phylogeny ,Aged ,Aged, 80 and over ,Genetics ,Antigens, Bacterial ,Helicobacter pylori ,Phylogenetic tree ,Cancer ,Bacteriology ,Sequence Analysis, DNA ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Vietnam ,bacteria ,Female - Abstract
The pathogenesis of gastroduodenal diseases is related to the diversity of H elicobacter pylori strains. CagA-positive strains are more likely to cause gastric cancer than CagA-negative strains. Based on EPIYA (Glu-Pro-Ile-Tyr-Ala) motifs at the carboxyl terminus corresponding to phosphorylation sites, H. pylori CagA is divided into East Asian CagA and Western CagA. The former type prevails in East Asia and is more closely associated with gastric cancer. The present study used full sequences of the cagA gene and CagA protein of 22 H. pylori strains in gastric cancer and peptic ulcer patients from Southern Vietnam to make a comparison of genetic homology among Vietnamese strains and between them and other strains in East Asia. A phylogenetic tree was constructed based on full amino acid sequences of 22 Vietnamese strains in accordance with 54 references from around the world. The cagA gene was found in all Vietnamese H. pylori strains. Twenty-one of 22 (95.5%) strains belonged to the East Asian type and had similar characteristics of amino acid sequence at the carboxyl terminus to other strains from the East Asian region. From evidence of East Asian CagA and epidemiologic cancerous lesions in Vietnam, H. pylori -infected Vietnamese can be classified into a high-risk group for gastric cancer, but further studies on the interaction among environmental and virulence factors should be done. Finally, phylogenetic data support that there is a Japanese subtype in the Western CagA type.
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- 2009
204. Image overlay navigation by markerless surface registration in gastrointestinal, hepatobiliary and pancreatic surgery
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Tohru Tezuka, Yohsuke Yagawa, Shuichiro Uemura, Hideki Yasuda, Keiji Koda, Hironori Tsuchiya, Yoshihisa Watayo, Masato Suzuki, Ryota Higuchi, Takeshi Azuma, Maki Sugimoto, Masato Yamazaki, and Chihiro Kosugi
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medicine.medical_specialty ,Colectomies ,Gastrointestinal Diseases ,Forceps ,Bile Duct Diseases ,DICOM ,Imaging, Three-Dimensional ,Body surface ,Humans ,Medicine ,Digestive System Surgical Procedures ,Hepatology ,business.industry ,Bile duct ,Pancreatic Diseases ,Reproducibility of Results ,Volume rendering ,Equipment Design ,Laparoscopes ,medicine.anatomical_structure ,Surgery, Computer-Assisted ,Surgery ,Augmented reality ,Radiology ,Tomography, X-Ray Computed ,business ,Abdominal surgery - Abstract
We applied a new concept of “image overlay surgery” consisting of the integration of virtual reality (VR) and augmented reality (AR) technology, in which dynamic 3D images were superimposed on the patient’s actual body surface and evaluated as a reference for surgical navigation in gastrointestinal, hepatobiliary and pancreatic surgery. We carried out seven surgeries, including three cholecystectomies, two gastrectomies and two colectomies. A Macintosh and a DICOM workstation OsiriX were used in the operating room for image analysis. Raw data of the preoperative patient information obtained via MDCT were reconstructed to volume rendering and projected onto the patient's body surface during the surgeries. For accurate registration, OsiriX was first set to reproduce the patient body surface, and the positional coordinates of the umbilicus, left and right nipples, and the inguinal region were fixed as physiological markers on the body surface to reduce the positional error. The registration process was non-invasive and markerlesss, and was completed within 5 min. Image overlay navigation was helpful for 3D anatomical understanding of the surgical target in the gastrointestinal, hepatobiliary and pancreatic anatomies. The surgeon was able to minimize movement of the gaze and could utilize the image assistance without interfering with the forceps operation, reducing the gap from the VR. Unexpected organ injury could be avoided in all procedures. In biliary surgery, the projected virtual cholangiogram on the abdominal wall could advance safely with identification of the bile duct. For early gastric and colorectal cancer, the small tumors and blood vessels, which usually could not be found on the gastric serosa by laparoscopic view, were simultaneously detected on the body surface by carbon dioxide-enhanced MDCT. This provided accurate reconstructions of the tumor and involved lymph node, directly linked with optimization of the surgical procedures. Our non-invasive markerless registration using physiological markers on the body surface reduced logistical efforts. The image overlay technique is a useful tool when highlighting hidden structures, giving more information.
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- 2009
205. Newly developed surface coil for endoluminal MRI, depiction of pig gastric wall layers and vascular architecture in ex vivo study
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Yoshinori Morita, Hideto Inokuchi, Takeshi Azuma, Masaru Yoshida, Hayato Yoshinaka, Hiromu Kutsumi, Kagayaki Kuroda, Etsuko Kumamoto, Yuichiro Matsuoka, Masakazu Gotanda, and Naomi Sekino
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Gadolinium DTPA ,Materials science ,medicine.diagnostic_test ,Stomach ,Sus scrofa ,Gastroenterology ,Contrast Media ,Muscle, Smooth ,Magnetic resonance imaging ,Anatomy ,In Vitro Techniques ,Muscle layer ,Image Enhancement ,Magnetic Resonance Imaging ,Vascular architecture ,medicine.anatomical_structure ,Gastric Mucosa ,Electromagnetic coil ,Silicone Elastomers ,medicine ,Surface coil ,Animals ,Gastric wall ,Ex vivo - Abstract
The purpose of this study was to visualize the gastric wall layers and to depict the vascular architecture in vitro by using resected porcine stomachs studied with high-spatial resolution magnetic resonance (MR) imaging. Normal dissected porcine stomach samples (n = 4) were examined with a 3 Tesla MR system using a newly developed surface coil. MR images were obtained by the surface coil as receiver and a head coil as transmitter. High-spatial-resolution spin-echo MR images were obtained with a field of view of 8 × 8 cm, a matrix of 256 × 128 and slice thicknesses of 3 and 5 mm. T1 and T2-weighted MR images clearly depicted the normal porcine gastric walls as consisting of four distinct layers. In addition, vascular architectures in proper muscle layers were also visualized, which were confirmed by histological examinations to correspond to blood vessels. High-spatial-resolution MR imaging using a surface coil placed closely to the gastric wall enabled the differentiation of porcine gastric wall layers and the depiction of the blood vessels in proper muscle layer in this experimental study.
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- 2009
206. Phase I and Pharmacokinetic Study of Tegafur-Uracil/Leucovorin Combined With 5-Fluorouracil/Leucovorin and Irinotecan in Patients With Advanced Colorectal Cancer
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Katsuhiko Okumura, Takeshi Azuma, Tatsuya Okuno, Hogara Nishisaki, Naoko Chayahara, Toshiyuki Sakaeda, Takao Tamura, Masato Kasuga, Yuko Kadowaki, Motohiro Yamamori, Midori Hirai, Masahiro Tsuda, Tetsuo Maeda, Yoshifumi Inoue, and Ikuya Miki
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Maximum Tolerated Dose ,Leucovorin ,Phases of clinical research ,Bone Neoplasms ,Adenocarcinoma ,Neutropenia ,Irinotecan ,Gastroenterology ,Tegafur ,Pharmacokinetics ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Tissue Distribution ,Survival rate ,Aged ,business.industry ,Liver Neoplasms ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Treatment Outcome ,Oncology ,Fluorouracil ,Lymphatic Metastasis ,Anesthesia ,FOLFIRI ,Camptothecin ,Female ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Objectives: FOLFIRI is one of the current standard first-line regimens for advanced colorectal cancer, but its administration is onerous. Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation. Methods: Treatment consisted of infusional irinotecan (100 mg/m 2 )/l-LV (15 mg/m 2 ) and a bolus injection of 5-FU (500 mg/m 2 ) on day 1, and oral UFT (300 mg as tegafur/m 2 /d)/LV (75 mg/d) on days 1-5 (level 1), days 1-7 (level 2), or days 1-10 (level 3). Cycles were repeated every 14 days. After determination of the recommended UFT/LV administration period, irinotecan was dose-escalated (level 4: 125 mg/m 2 ; level 5: 150 mg/m 2 ). Results: Nineteen patients were enrolled. One dose-limiting toxicity (DLT), grade 4 neutropenia lasting for ≥4 days was observed at level 2. At level 3, one DLT of treatment delay of ≥8 days occurred due to prolonged neutropenia, and 2 patients refused to continue the treatment because of prolonged grade 2 anorexia. Therefore, a 7-day administration of UFT/LV was recommended. No DLT was observed at levels 4 and 5. Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination. Conclusions: The recommended administration period was 7 days for oral UFT/LV, and the recommended dose of irinotecan was 150 mg/m 2 . A phase II study is ongoing to validate the clinical outcome.
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- 2009
207. The Effects of Helicobacter pylori Eradication on Body Mass Index and Dyspeptic Symptoms
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Ikumi Yoshida, Yoshiyuki Ito, Akiyo Yamakawa, Takeshi Azuma, Takuji Kato, Yukinao Yamazaki, Masahiro Ohtani, Masaru Kuriyama, and Hiroyuki Suto
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medicine.medical_specialty ,biology ,Atrophic gastritis ,business.industry ,Stomach ,Gastroenterology ,Helicobacter pylori ,medicine.disease ,Helicobacter Infections ,biology.organism_classification ,medicine.anatomical_structure ,Pharmacotherapy ,Internal medicine ,medicine ,Gastritis ,medicine.symptom ,business ,Body mass index - Abstract
Background and Aim: The relationship between Helicobacter pylori infection and body mass index (BMI) and dyspeptic symptoms is controversial. We investigated the changes in BMI and dyspeptic symptoms after H. pylori eradication among stages of atrophic gastritis classified according to the serum pepsinogen (PG) I/II ratio. Methods: One hundred and sixty-three H. pylori-positive patients underwent eradication therapy for H. pylori. Serum PG I and II concentrations were measured before treatment, and the PG I/II ratio was classified into three groups: PG I/II ratio Results: The mean BMI changes 1 year after treatment in the low PG I/II ratio group were significantly higher than those in other groups. Most abdominal symptoms in the high PG I/II ratio group were most severe before eradication but improved significantly after eradication. Conclusions: The effects of H. pylori eradication on BMI and dyspeptic symptoms may be different according to the serum PG I/II ratio before eradication.
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- 2009
208. Contents Vol. 79, 2009
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Toshifumi Hibi, Hiroshi Nakase, Kensuke Kubota, Kumiko Saito, Yuriko Minegishi, Gundula Straub, Dieter Jüngst, Berthold Schneider, Nobutaka Fujisawa, Yoshihisa Tsuji, Yasser A. Alderlieste, Yoshiyuki Ito, Hiroshi Ichikawa, Yusuke Sekino, Emanuel Burri, Katsura Mizushima, Yukinao Yamazaki, Michael Neubrand, Dirk P. van Asseldonk, Etsuko Kishimoto, Michiro Otaka, Thomas P. Hüttl, Fritz Spelsberg, Sakae Mikami, Fumiyasu Nakamura, Satoshi Kokura, Ikuhiro Hirata, Masahiro Ohtani, Satoru Saito, Keiko Akimoto, Hédia Benmansour, Atsushi Nakajima, Shigeru Koyama, Hirofumi Hara, Ayako Tomimoto, Osamu Handa, Rupert Althaus, Reginald del Pozo, Toshikazu Yoshikawa, Ulrich Beuers, Izumi Nakagawa, Michael Manz, Takeshi Azuma, Ikumi Yoshida, Lukas Degen, Takuji Kato, Stéphane Nancey, Masahiko Inamori, Tatsushi Omatsu, Erik A.J. Rauws, Tetsuya Okayama, Tsutomu Chiba, Yoshihide Ueda, Stephan R. Vavricka, Masaru Kuriyama, Satoko Adachi, Yoshiaki Ohara, Hidekazu Suzuki, Eisuke Iwasaki, Bram D.J. van den Elzen, Denis Gründel, Kouhei Yamashita, Tomohisa Takagi, Tomohiro Watanabe, Sylvette Claudel, Christoph Beglinger, Natsuko Hayashi, Bernard Flourié, Yuji Naito, Atsushi Nakamura, Tatsuhiro Masaoka, Sabine Roman, Kaori Suzuki, Akiyo Yamakawa, Hiroyuki Suto, Bernardina M. Kanis, Ad A. van Bodegraven, Kimiko Hori, Christoph Jüngst, Tomoyuki Akiyama, Driffa Moussata, Toshihiro Nishizawa, and Nanne K. H. de Boer
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Gastroenterology - Published
- 2009
209. High Prevalence of Irritable Bowel Syndrome in Medical Outpatients in Japan
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Tetsuo Arakawa, Ken Haruma, Shigeru Kitamori, Masae Shinozaki, Takeshi Azuma, Michio Hongo, Shin Fukudo, Daisuke Sasaki, Masanori Handa, Tetsuya Mine, Soichiro Miura, Akira Torii, Mikihiko Fukunaga, Tooru Shimosegawa, Kei Matsueda, Hiroto Miwa, Hiroshi Kaneko, Shigeru Harasawa, and Takeshi Miwa
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Disease ,Severity of Illness Index ,Irritable Bowel Syndrome ,Japan ,Surveys and Questionnaires ,Outpatients ,Severity of illness ,Epidemiology ,Prevalence ,Humans ,Medicine ,Life Style ,Irritable bowel syndrome ,Aged ,Aged, 80 and over ,High prevalence ,business.industry ,Life style ,Age Factors ,Gastroenterology ,Middle Aged ,medicine.disease ,Psychosocial stress ,Ambulatory ,Female ,business ,Stress, Psychological - Abstract
Background and Goals: The prevalence of irritable bowel syndrome (IBS) among Japanese patients who visit hospitals departments of internal medicine is thought to be high. However, no clear statistical evidence has been provided to support such a claim. We tested the hypotheses that the prevalence of IBS in medical outpatients clinics in Japan is high, and that IBS patients feel more psychosocial stress than patients without IBS. Study: The subjects in this study were 633 patients who visited participating physicians. Patients were asked to fill in the Japanese version of the Rome II Modular Questionnaire (RIIMQ) for IBS diagnosis, the Self-reported Irritable Bowel Syndrome Questionnaire (SIBSQ) for severity of the disease and the demographic questionnaire for perceived stress and life style. Results: Rome II-defined IBS was diagnosed in 196 patients (31%). Analysis of variance revealed significant difference in the IBS scores of SIBSQ among IBS subjects (39.0 ± 11.1, mean ± SD), functional bowel disorder subjects (27.1 ± 10.2), and normal subjects (24.0 ± 10.0, P < 0.01). The prevalence of IBS depending on age formed 2 peaks, one among adolescents and the other among the elderly. IBS patients had significantly more perceived stress (P < 0.0001), irregular sleep habit (P < 0.0001), and irregular meal habit (P < 0.0001) than those without IBS. Conclusions: The prevalence of IBS among medical outpatients in Japan is high (31%). IBS subjects among medically ill patients are thought to have more perceived stress and less regular life styles.
- Published
- 2008
210. Role of metallothionein inHelicobacter pylori-positive gastric mucosa with or without early gastric cancer and the effect on its expression after eradication therapy
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Hideyuki Miyachi, Takao Tamura, Toshifumi Mitani, Yoshinori Morita, Tatsuya Okuno, Nobunao Ikehara, Junko Hori, Masanori Toyoda, Shiei Yoshida, Ikuya Miki, Daisuke Shirasaka, Takeshi Azuma, Nobuo Aoyama, Yuko Matsumoto, Masato Kasuga, and Naoko Chayahara
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medicine.medical_specialty ,Pathology ,Gastroenterology ,Helicobacter Infections ,Stomach Neoplasms ,Internal medicine ,Biopsy ,Gastric mucosa ,medicine ,Humans ,Antrum ,Helicobacter pylori ,Hepatology ,biology ,medicine.diagnostic_test ,business.industry ,Cancer ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,Early Gastric Cancer ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,Gastric Mucosa ,Metallothionein ,Gastritis ,medicine.symptom ,business - Abstract
Background and Aim: Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy. Methods: Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years. Results: MT expression was higher in H. pylori-negative patients than in positive patients (P
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- 2008
211. Fcγ Receptor Regulation of Citrobacter rodentium Infection
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Hiroshi Tanaka, Satoshi Ikezawa, Toshiyuki Takai, Atsuhiro Masuda, Hideto Inokuchi, Ryo Chinzei, Takeshi Azuma, Shuo Wang, Richard S. Blumberg, Akira Nakamura, Tetsuya Takagawa, Kanna Kobayashi, Masaru Yoshida, Hiromu Kutsumi, Yoshinori Morita, Tsukasa Ishida, Shigeto Mizuno, and Hideyuki Shiomi
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T-Lymphocytes ,Phagocytosis ,Immunology ,Fc receptor ,Lymphocyte Activation ,digestive system ,Microbiology ,Immunoglobulin G ,Mice ,Neonatal Fc receptor ,Citrobacter rodentium ,Animals ,Receptor ,Common gamma chain ,Host Response and Inflammation ,biology ,Macrophages ,Receptors, IgG ,Enterobacteriaceae Infections ,Dendritic Cells ,Intestinal epithelium ,Infectious Diseases ,Gene Expression Regulation ,biology.protein ,Cytokines ,Parasitology ,Disease Susceptibility - Abstract
Citrobacter rodentium , a murine model pathogen for enteropathogenic Escherichia coli , colonizes the colon utilizing attaching and effacing lesions to adhere specifically to the surfaces of intestinal epithelial cells and cause mucosal inflammation. CD4 + T cells, B cells, and immunoglobulin G (IgG), but not secretory IgA or IgM, play a critical role in eradicating this pathogen. Consistent with the importance of IgG in C . rodentium eradication, IgG transport by the neonatal Fc receptor for IgG within the intestinal epithelium also has a critical role in the regulation of C . rodentium infection. It remains to be determined, however, whether Fcγ receptors (FcγRs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of FcγRs during C . rodentium infection. Fc receptor common gamma chain (FcRγ)-deficient mice were more susceptible to C . rodentium -induced colitis. This occurred through decreased efficiency of FcR-mediated endocytosis and maturation of dendritic cells and consequently T-cell activation of antigen-specific T cells. Moreover, in the absence of FcγRs, phagocytosis by macrophages was significantly diminished. Therefore, activating FcγRs play an important role in defending against C . rodentium infection, indicating that the critical role played by IgG in this infection is not mediated by IgG alone but is dependent upon this class of receptors.
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- 2008
212. Asia–Pacific consensus guidelines on gastric cancer prevention
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Hazel M. Mitchell, Naomi Uemura, Shu Dong Xiao, Takeshi Azuma, Jose D. Sollano, Ratha korn Vilaichone, Tsutomu Chiba, Paul Moayyedi, Nicholas J. Talley, Richard H. Hunt, Kentaro Sugano, Jae G. Kim, Khean-Lee Goh, Varocha Mahachai, Jyh-Ming Liou, Shiu Kum Lam, Abdul Aziz Rani, Nayoung Kim, Tiing Leong Ang, and Kwong Ming Fock
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Oncology ,medicine.medical_specialty ,Asia ,Atrophic gastritis ,Ascorbic Acid ,Adenocarcinoma ,Pacific Islands ,Risk Assessment ,Gastroenterology ,Helicobacter Infections ,Risk Factors ,Stomach Neoplasms ,Internal medicine ,Vegetables ,Biomarkers, Tumor ,Prevalence ,medicine ,Anticarcinogenic Agents ,Humans ,Mass Screening ,Genetic Predisposition to Disease ,Sodium Chloride, Dietary ,Family history ,Risk factor ,Stomach cancer ,Evidence-Based Medicine ,Helicobacter pylori ,Pepsinogens ,Hepatology ,biology ,business.industry ,Incidence ,digestive, oral, and skin physiology ,Cancer ,Vitamins ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Anti-Bacterial Agents ,Pedigree ,Fruit ,Dietary Supplements ,Gastric acid ,Risk assessment ,business - Abstract
Background and Aim: Gastric cancer is a major health burden in the Asia–Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. Methods: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Results: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host–bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines. Conclusion: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.
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- 2008
213. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse
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Motohiro Miura, Kazuya Iwabuchi, Masanori Hatakeyama, Misao Suzuki, Gen Yamada, Takeshi Azuma, Naomi Ohnishi, Hirofumi Sawa, Atsushi Matsui, Hideaki Higashi, Shinya Tanaka, Manabu Musashi, and Hitomi Yuasa
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Mice, Transgenic ,Protein tyrosine phosphatase ,Biology ,medicine.disease_cause ,digestive system ,Mice ,chemistry.chemical_compound ,Bacterial Proteins ,medicine ,Animals ,CagA ,Neoplastic transformation ,Secretion ,Phosphotyrosine ,B cell ,Gastrointestinal Neoplasms ,Antigens, Bacterial ,Multidisciplinary ,Helicobacter pylori ,Tyrosine phosphorylation ,Biological Sciences ,bacterial infections and mycoses ,biology.organism_classification ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,chemistry ,Hematologic Neoplasms ,Cancer research ,bacteria ,Carcinogenesis - Abstract
Infection with cagA -positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA -encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase, a bona fide oncoprotein in human malignancies. CagA also elicits junctional and polarity defects in epithelial cells by interacting with and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) independently of CagA tyrosine phosphorylation. Despite these CagA activities that contribute to neoplastic transformation, a causal link between CagA and in vivo oncogenesis remains unknown. Here, we generated transgenic mice expressing wild-type or phosphorylation-resistant CagA throughout the body or predominantly in the stomach. Wild-type CagA transgenic mice showed gastric epithelial hyperplasia and some of the mice developed gastric polyps and adenocarcinomas of the stomach and small intestine. Systemic expression of wild-type CagA further induced leukocytosis with IL-3/GM-CSF hypersensitivity and some mice developed myeloid leukemias and B cell lymphomas, the hematological malignancies also caused by gain-of-function SHP-2 mutations. Such pathological abnormalities were not observed in transgenic mice expressing phosphorylation-resistant CagA. These results provide first direct evidence for the role of CagA as a bacterium-derived oncoprotein (bacterial oncoprotein) that acts in mammals and further indicate the importance of CagA tyrosine phosphorylation, which enables CagA to deregulate SHP-2, in the development of H. pylori -associated neoplasms.
- Published
- 2008
214. Changing Antimicrobial Susceptibility Epidemiology of Helicobacter pylori Strains in Japan between 2002 and 2005
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Masaru Nasu, Takeshi Azuma, Naomi Uemura, Tsutomu Katsuyama, Ken Haruma, Shin'ichi Takahashi, Seiichi Kato, Intetsu Kobayashi, Toshio Fujioka, Yoshihiro Fukuda, Kazunari Murakami, and Mototsugu Kato
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Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,Epidemiology ,Spirillaceae ,Population ,Microbial Sensitivity Tests ,Drug resistance ,Helicobacter Infections ,Sex Factors ,Japan ,Clarithromycin ,Metronidazole ,Internal medicine ,Drug Resistance, Bacterial ,medicine ,Humans ,Child ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,Helicobacter pylori ,biology ,business.industry ,Amoxicillin ,Middle Aged ,Antimicrobial ,biology.organism_classification ,Anti-Bacterial Agents ,Gastric Mucosa ,Immunology ,Female ,business ,medicine.drug - Abstract
Surveillance of Helicobacter pylori antimicrobial susceptibility reflecting the general population in Japan is limited. The antimicrobial susceptibilities of 3,707 H. pylori strains isolated from gastric mucosa samples of previously untreated patients diagnosed with gastroduodenal diseases at 36 medical facilities located throughout Japan between October 2002 and September 2005 were evaluated. Using an agar dilution method for antimicrobial susceptibility testing of H. pylori , the MIC distributions and trends during the study period for clarithromycin, amoxicillin, and metronidazole were studied. While the MIC 50 and MIC 90 for clarithromycin did not change during the 3-year period, the MIC 80 showed a 128-fold increase. Furthermore, the rate of resistance increased yearly from 18.9% (2002 to 2003) to 21.1% (2003 to 2004) and 27.7% (2004 to 2005). With a resistance rate of 19.2% among males compared to 27.0% among females, a significant gender difference was observed ( P < 0.0001). Our study shows that in Japan, there is an evolving trend towards increased resistance to clarithromycin with geographical and gender differences as well as between clinical disease conditions. No significant changes in resistance were observed for amoxicillin and metronidazole during the period. While the benefit of H. pylori antimicrobial susceptibility testing has been debated in Japan, current empirical regimens are not based on susceptibility data representative of the general population. The development of an effective H. pylori eradication regimen in Japan will require continued resistance surveillance as well as a better understanding of the epidemiology of resistance.
- Published
- 2007
215. High prevalence of neutralizing activity to helicobacter pylori cytotoxin in serum of gastric-carcinoma patients
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Yoshihiro Kohli, M. Hirai, Norio Fujiki, Takeshi Azuma, Takuji Kato, and Shigeji Ito
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Adult ,Male ,Cancer Research ,Biopsy ,Spirillaceae ,Bacterial Toxins ,Blotting, Western ,Helicobacter Infections ,Pathogenesis ,Bacterial Proteins ,Japan ,Western blot ,Neutralization Tests ,Stomach Neoplasms ,Prevalence ,medicine ,Carcinoma ,Humans ,Stomach Ulcer ,Aged ,Retrospective Studies ,Helicobacter pylori ,biology ,medicine.diagnostic_test ,Stomach ,Middle Aged ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,Antibodies, Bacterial ,digestive system diseases ,medicine.anatomical_structure ,Oncology ,Gastric Mucosa ,Immunology ,biology.protein ,Female ,Antibody ,Gastritis ,medicine.symptom ,HeLa Cells - Abstract
Helicobacter pylori infection is causally related to chronic type-B gastritis, and may also be associated with an increased risk of gastric carcinoma. Vacuolating cytotoxin, which is an 87-kDa protein secreted by H. pylori, induces eukaryotic cell vacuolation in vitro. To determine whether there is an association between H. pylori vacuolating cytotoxin and gastric carcinoma, we investigated several characteristics of H. pylori infection, i.e., isolation of H. pylori from gastric biopsies, antibodies specific for H. pylori, detection of neutralizing activity to vacuolating cytotoxin in serum and immunological detection of cytotoxin by serum. Out of 6 sera from gastric-carcinoma patients, all showed the neutralizing activity to vacuolating cytotoxin, in contrast to 3 of 5 sera from peptic-ulcer patients. Normal individuals showed no neutralizing activity. All sera possessing the neutralizing activity recognized an 87-kDa protein band by Western blot analysis. Our results confirmed that cytotoxin-neutralizing activity in human sera was associated with immunodetection of an 87-kDa protein. To further evaluate neutralizing activity in serum from gastric-carcinoma patients, we retrospectively analyzed frozen-stocked serum samples from 22 gastric-carcinoma patients. Sera from 21 of these 22 patients exhibited neutralizing activity. These sera were also checked for antibodies to H. pylori, using an ELISA; 16 sera showed positive results. Our results indicate that detection of cytotoxin-neutralizing activity in sera is strongly associated with H. pylori infection, and probably with gastric carcinoma, and is also of interest in the diagnosis of H. pylori infection. © 1994 Wiley-Liss, Inc.
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- 2007
216. COMPLICATIONS OF ENDOSCOPIC SPHINCTEROTOMY FOR CHOLEDOCHOLITHIASIS: SAFETY AND BENEFITS OF PANCREATIC STENT PREPLACEMENT
- Author
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Masaru Yoshida, Yoshinori Morita, Hideto Inokuchi, Hiromu Kutsumi, Eiji Funatsu, and Takeshi Azuma
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medicine.medical_specialty ,Endoscopic retrograde cholangiopancreatography ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Gastroenterology ,food and beverages ,Stent ,Retrospective cohort study ,Argon plasma coagulation ,Clipping (medicine) ,medicine.disease ,Pancreatic stent ,Pancreatic duct stent ,medicine ,Pancreatitis ,Radiology, Nuclear Medicine and imaging ,Radiology ,business - Abstract
Endoscopic sphincterotomy (EST) is one of the most common procedures for treatment of choledocholithiasis. However, EST sometimes causes complications such as pancreatitis and bleeding. Especially, precut is more risky for pancreatitis. In contrast, bleeding after EST should be treated immediately. Clipping technique is the ideal method for bleeding but is very difficult technically. The authors have carried out precut with needle knife and treated bleeding with argon plasma coagulation after placement of pancreatic duct stent (PS) to prevent pancreatitis. This retrospective study showed the safety and benefit of stent preplacement for these two representative problems. Complications in 174 patients with choledocholithiasis treated by EST were collected and investigated retrospectively. In total, 92% were standard EST, 8% were precut over PS. Pancreatitis occurred in 13.1% of the standard EST group and in 7.1% of the precut over PS group. Bleeding after EST occurred in three cases (1.7%). Two patients were treated easily and safely by argon plasma coagulation after placement of PS.
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- 2007
217. Favorable Genetic Polymorphisms Predictive of Clinical Outcome of Chemoradiotherapy for Stage II/III Esophageal Squamous Cell Carcinoma in Japanese
- Author
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Naoko Chayahara, Tatsuya Okuno, Masato Kasuga, Takao Tamura, Katsuhiko Okumura, Takeshi Azuma, Tsutomu Nakamura, Ikuya Miki, Toshiyuki Sakaeda, Daisuke Shirasaka, Yuko Kadowaki, Toshio Yamada, Motohiro Yamamori, Noboru Okamura, and Nobuo Aoyama
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Esophageal Neoplasms ,medicine.medical_treatment ,Stage ii ,Esophageal squamous cell carcinoma ,Asian People ,Polymorphism (computer science) ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma ,Humans ,Medicine ,Combined Modality Therapy ,neoplasms ,Aged ,Aged, 80 and over ,Cisplatin ,Polymorphism, Genetic ,Radiotherapy ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,digestive system diseases ,Radiation therapy ,Carcinoma, Squamous Cell ,Female ,Fluorouracil ,business ,Chemoradiotherapy ,medicine.drug - Abstract
This study was performed to find the genetic factors predictive of clinical outcome to a 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC).Thirty-one patients with stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions (PVIs) of 5-FU (400 mg/m2/24 hours for days 1-5 and 8-12), CDDP (40 mg/m2/3 hours on days 1 and 8) and radiation (2 Gy/d on days 1-5, 8-12, and 15-19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1), multidrug resistant transporter MDR1/P-glycoprotein, and intercellular adhesion molecule-1, and in a circadian rhythm-relating gene, CLOCK.The CR rate depended on stage (P = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (P = 0.061). For stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5'-TSER, a 6 bp of 3'-TSUTR, and GSTP1-Ile105Val resulted in an extensively longer survival (P = 0.020), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinicopathologic characteristics.The prognostic index may allow predictions of the clinical outcome of a 5-FU/CDDP-based CRT in stage II/III ESCC patients.
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- 2007
218. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium
- Author
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Il-mi Okazaki, Hiroyuki Marusawa, Kazuo Kinoshita, Yoko Endo, Takeshi Azuma, Toshiyuki Morisawa, Yuko Matsumoto, Tasuku Honjo, Tsutomu Chiba, and Tadayuki Kou
- Subjects
Tumor suppressor gene ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Helicobacter Infections ,Bacterial Proteins ,Downregulation and upregulation ,Stomach Neoplasms ,Cytidine Deaminase ,Gastric mucosa ,medicine ,Activation-induced (cytidine) deaminase ,Humans ,DNA Primers ,Regulation of gene expression ,Antigens, Bacterial ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,NF-kappa B ,General Medicine ,Cytidine deaminase ,Helicobacter pylori ,Genes, p53 ,biology.organism_classification ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Transplantation ,medicine.anatomical_structure ,Gastric Mucosa ,Mutagenesis ,Immunology ,Cancer research ,biology.protein ,business ,Signal Transduction - Abstract
Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IkappaB kinase-dependent nuclear factor-kappaB activation pathway. H. pylori-mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis.
- Published
- 2007
219. Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells
- Author
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Seishi Ogawa, Kyoichi Tomita, Tsuyoshi Takahashi, Mineo Kurokawa, Akihiko Matsumoto, Kyoko Haraguchi, Yoshinobu Kanda, Takeshi Azuma, Shigeru Chiba, Koki Takahashi, and Tadaichi Kitamura
- Subjects
Pathology ,medicine.medical_specialty ,biology ,business.industry ,Urology ,medicine.medical_treatment ,ELISPOT ,Interleukin ,Immunotherapy ,medicine.disease ,Primary tumor ,Antigen ,Interferon ,Renal cell carcinoma ,biology.protein ,Medicine ,business ,Keyhole limpet hemocyanin ,medicine.drug - Abstract
Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC). Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-α treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging. Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation. Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria.
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- 2007
220. Hypoxia-inducible factor-1 alpha and vascular endothelial growth factor expression in ischaemic colitis and ulcerative colitis
- Author
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Soshoku Lee, Takeshi Azuma, Hiroyuki Suto, Masaru Kuriyama, Yoshiyuki Ito, Yukinao Yamazaki, Shinsuke Matsunaga, Ryuho Masaki, Satoko Satomi, Masahiro Ohtani, Tomoyuki Okuda, T. Inagaki, Atsushi Muramatsu, and Shigeji Ito
- Subjects
Hepatology ,business.industry ,Gastroenterology ,Vegf expression ,medicine.disease ,Ulcerative colitis ,Vascular endothelial growth factor ,Hypoxia-Inducible Factor 1-Alpha ,chemistry.chemical_compound ,HIF1A ,chemistry ,medicine ,Cancer research ,Pharmacology (medical) ,Colitis ,business - Published
- 2007
221. Prescription of Nonsteroidal Anti-inflammatory Drugs and Co-prescribed Drugs for Mucosal Protection: Analysis of the Present Status Based on Questionnaires Obtained from Orthopedists in Japan
- Author
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Hiroshi Tanaka, Masaru Yoshida, Ryo Chinzei, Hiromu Kutsumi, Masahiro Kurosaka, Minoru Doita, Atsuhiro Masuda, Takeshi Azuma, Hideyuki Shiomi, Hidetaka Tsumura, Isamu Tamura, Yoshinori Morita, Tsukasa Ishida, and Hideto Inokuchi
- Subjects
Adult ,Male ,Drug ,Drug Utilization ,Peptic Ulcer ,medicine.medical_specialty ,Attitude of Health Personnel ,medicine.drug_class ,media_common.quotation_subject ,Proton-pump inhibitor ,Pharmacology ,Pharmacotherapy ,Japan ,Surveys and Questionnaires ,Internal medicine ,Internal Medicine ,Humans ,Medicine ,Musculoskeletal Diseases ,Practice Patterns, Physicians' ,Medical prescription ,Adverse effect ,media_common ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Proton Pump Inhibitors ,General Medicine ,Diclofenac Sodium ,Loxoprofen ,Middle Aged ,Anti-Ulcer Agents ,Primary Prevention ,Orthopedics ,Histamine H2 Antagonists ,Gastric Mucosa ,Health Care Surveys ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Objective Recently guidelines for the treatment and prevention of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) have been established. The aim of the present study was to examine factors influencing orthopedists in Japan in the use of cytoprotective drugs to prevent NSAID-associated gastrointestinal adverse events. Methods We sent a questionnaire to 402 orthopedists in Hyogo Prefecture. A standardized 10-item questionnaire was used to collect information on NSAID prescriptions (drug name, pharmaceutical form, doses, and duration of use) and associated drugs, especially gastroprotective drugs. Results Two hundred eight (51.7%) orthopedists returned the questionnaire. The most frequently used NSAIDs, in descending order, were loxoprofen sodium, diclofenac sodium, and etodolac. Most doctors (80%) reported patients with abdominal symptoms associated with NSAIDs. Of these doctors, 59% treated the symptoms by themselves, and prescribed gastroprotective agents (32.2%), histamine H2-receptor antagonists (H2RAs) (26.4%), prostaglandin analogues (PAs) (17.0%), or proton pump inhibitors (PPIs) (16.2%). Sixty-seven percent of doctors reported that those drugs reduced the symptoms. Most orthopedists (96%) prescribed some type of drug to prevent NSAID-associated gastrointestinal events, including gastroprotective drugs (44.6%), H2RAs (19.5%), PAs (17.4%), and PPIs (10.8%). The doctors reported that they prescribed medicines for NSAID-associated gastrointestinal events on the basis of their experience (23%), by considering medical insurance restrictions (17%), and by referring to information provided by pharmaceutical company representatives (16%). Conclusion Most orthopedists prescribe some type of drug to prevent NSAID-induced ulcers but do not refer to the guidelines. We therefore strongly recommend that the guidelines be made more widely known to gastroenterologists and to physicians in every field of clinical practice, including orthopedics.
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- 2007
222. Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients
- Author
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Yasuhito Tanaka, Tran Minh Phuong, Takako Utsumi, Yoshihiko Yano, Yasushi Seo, Hirotaka Kato, Masashi Mizokami, Yoshitake Hayashi, Bui Xuan Truong, Nguyen Khanh Trach, Akira Miki, Masato Kasuga, and Takeshi Azuma
- Subjects
Adult ,Liver Cirrhosis ,Male ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Genotype ,Vietnamese ,medicine.disease_cause ,Liver disease ,Japan ,Orthohepadnavirus ,Risk Factors ,Virology ,Humans ,Medicine ,Hepatitis B e Antigens ,Promoter Regions, Genetic ,Phylogeny ,Molecular Epidemiology ,biology ,business.industry ,Liver Neoplasms ,Middle Aged ,Hepatitis B ,biology.organism_classification ,medicine.disease ,digestive system diseases ,language.human_language ,Cross-Sectional Studies ,Infectious Diseases ,Vietnam ,Hepadnaviridae ,Hepatocellular carcinoma ,DNA, Viral ,language ,Female ,business ,Asymptomatic carrier ,Polymorphism, Restriction Fragment Length - Abstract
Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P < 0.05). Most of the Vietnamese patients with HCC had a high level of HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients.
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- 2007
223. Deregulation of β-catenin signal byHelicobacter pylori CagA requires the CagA-multimerization sequence
- Author
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Naoko Murata-Kamiya, Satoshi Kondo, Kenji Kikuchi, Hideaki Higashi, Takeshi Azuma, Yo Kurashima, and Masanori Hatakeyama
- Subjects
Cancer Research ,Blotting, Western ,Protein tyrosine phosphatase ,Biology ,digestive system ,Gene product ,chemistry.chemical_compound ,Bacterial Proteins ,Stomach Neoplasms ,medicine ,Humans ,CagA ,Intestinal Mucosa ,beta Catenin ,Antigens, Bacterial ,Intestinal metaplasia ,Tyrosine phosphorylation ,Helicobacter pylori ,Cadherins ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Molecular biology ,digestive system diseases ,Cell Transformation, Neoplastic ,Oncology ,chemistry ,Catenin ,Immunology ,bacteria ,Gastritis ,medicine.symptom ,Dimerization ,Precancerous Conditions - Abstract
Infection with Helicobacter pylori cagA-positive strains causes gastritis and peptic ulceration and is associated with gastric adenocarcinoma. The cagA gene product CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases at the C-terminal EPIYA-repeat region. Tyrosine-phosphorylated CagA specifically binds and activates SHP-2 tyrosine phosphatase, causing cell morphological transformation known as the hummingbird phenotype. CagA also destabilizes the E-cadherin/β-catenin complex to elicit aberrant activation of the β-catenin signal that underlies intestinal metaplasia. Here we show that translocalization of membranous β-catenin and subsequent activation of the β-catenin signal by CagA requires the EPIYA-repeat region, which is characterized by structural variation between CagA of H. pylori isolated in Western countries (Western CagA) and that of East Asian H. pylori isolates (East Asian CagA), but is independent of CagA tyrosine phosphorylation. Detailed analysis using a series of Western and East Asian CagA mutants revealed that deregulation of β-catenin requires residues 1009–1086 and residues 908–1012 of ABCCC Western CagA and ABD East Asian CagA, respectively, and is mediated by the 16-amino-acid CagA multimerization sequence that is conserved between the 2 geographically distinct H. pylori CagA species. Our results indicate that aberrant activation of the β-catenin signal, which promotes precancerous intestinal metaplasia, is an inherent and fundamental CagA activity that is independent of the structural polymorphism of CagA. © 2007 Wiley-Liss, Inc.
- Published
- 2007
224. Pancreatic Arteriovenous MalformationCombined with Portal Thrombosis
- Author
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Ikuyo Takemoto, Masato Kasuga, Sakan Maeda, Hiroyuki Yamada, Takeshi Azuma, Takatoshi Nakajima, Hiroyuki Miyazaki, Masahiro Tsuda, and Yoshihiko Yano
- Subjects
Male ,Radiography, Abdominal ,medicine.medical_specialty ,Hemorrhage ,Esophageal and Gastric Varices ,Arteriovenous Malformations ,Fatal Outcome ,Esophageal varices ,Celiac Artery ,Mesenteric Artery, Superior ,Celiac artery ,medicine.artery ,Sclerotherapy ,Internal Medicine ,medicine ,Humans ,Thrombus ,Pancreas ,Aged ,Ultrasonography ,Venous Thrombosis ,medicine.diagnostic_test ,Portal Vein ,business.industry ,Angiography ,Endoscopy ,Arteriovenous malformation ,Phlebography ,General Medicine ,medicine.disease ,Aneurysm ,Portal vein thrombosis ,Venous thrombosis ,Portal hypertension ,Radiology ,Tomography, X-Ray Computed ,business - Abstract
We encountered a case of portal vein thrombosis (PVT) after treatment for portal hypertension due to pancreatic arteriovenous malformation (PAVM). A 75-year-old man was admitted for the treatment of esophageal varices. Diffuse PAVM and aneurysm in the celiac and superior mesenteric arteries were detected via abdominal computed tomography and angiography. Although endoscopical sclerotherapy was performed, PVT was identified after the treatment and variceal bleeding continued. Autopsy was performed and the thrombus and malformation were pathologically confirmed. This case indicates that PVT can be associated with PAVM.
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- 2007
225. Risk of stricture after endoscopic submucosal dissection for large rectal neoplasms
- Author
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Tetsuya Yoshizaki, Alisara Damrongmanee, Shinwa Tanaka, Tsukasa Ishida, Yoshinori Morita, Ka Luen Lui, Takeshi Azuma, Mitsuru Nagata, Namiko Hoshi, Fumiaki Kawara, Yoshiko Ohara, Kanokkan Tepmalai, Takashi Toyonaga, and Eiji Umegaki
- Subjects
Adenoma ,Male ,medicine.medical_specialty ,Colonoscopy ,Rectum ,Adenocarcinoma ,Rectal Tumors ,Postoperative Complications ,Risk Factors ,medicine ,Humans ,Intestinal Mucosa ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Rectal Neoplasms ,Gastroenterology ,Clinical course ,Retrospective cohort study ,Endoscopic submucosal dissection ,Middle Aged ,University hospital ,medicine.disease ,Surgery ,Stenosis ,medicine.anatomical_structure ,Logistic Models ,Treatment Outcome ,Female ,business ,Intestinal Obstruction ,Follow-Up Studies - Abstract
Improvements in the endoscopic submucosal dissection (ESD) technique have made circumferential ESD in the rectum possible. However, little is known about the clinical course after extensive ESD in the rectum. The aim of this study was to determine the stricture risk in the rectum after total or subtotal circumferential ESD.A total of 69 patients with 69 rectal tumors that required ≥ 75 % circumferential resection were identified at Kobe University Hospital and an affiliated hospital between April 2005 and May 2014. Among the patients, 61 were available for evaluation of stricture development, either by follow-up colonoscopy or by surgical specimens. The rate and possible risk factors of post-ESD strictures were investigated.Post-ESD rectal strictures developed in 12 patients (19.7 %). Patients who underwent total circumferential ESD developed a stricture (5/7, 71.4 %) more frequently than those with subtotal (≥ 90 %) ESD (7/16, 43.8 %). Patients undergoing an ESD procedure that involved 90 % of the circumference did not develop strictures. The strictures were membranous or 10 mm long in all cases. Of the patients with stricture, 11 received endoscopic balloon dilation and one received bougie with short-caliber-tip transparent hood; all strictures improved following dilation therapy. Statistical analysis revealed that ≥ 90 % circumferential resection was an independent risk factor for stricture, whereas morphology and size were not.Patients who underwent total or subtotal circumferential ESD of a rectal tumor had a high risk of stricture formation. Dilation helped to alleviate the stenosis.Study registered at University Hospital Medical Information Network (UMIN 000016559).
- Published
- 2015
226. Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium
- Author
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Katsuya Okawa, Hideki Okazawa, Mariko Takeda-Morishita, Miki Nishio, Edwin Widyanto Daniwijaya, Yasuyuki Saito, Shinya Imada, Kohichi Kawahara, Shinya Kusakari, Takenori Kotani, Takeshi Azuma, Hisanobu Sadakata, Yoji Murata, Yana Supriatna, Takashi Matozaki, Akira Suzuki, Yoshitake Kanazawa, Hiroshi Ohnishi, Munemasa Mori, and Yasuaki Kitamura
- Subjects
Male ,Colon ,Cell Count ,Protein tyrosine phosphatase ,Receptor tyrosine kinase ,src Homology Domains ,Mice ,chemistry.chemical_compound ,Intestinal mucosa ,Animals ,Humans ,Syk Kinase ,RNA, Messenger ,Intestinal Mucosa ,Phosphorylation ,Phosphotyrosine ,Multidisciplinary ,biology ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,Intracellular Signaling Peptides and Proteins ,NF-kappa B ,Tyrosine phosphorylation ,Protein-Tyrosine Kinases ,Colitis ,FLT4 ,Intestinal epithelium ,Interleukin-10 ,Cell biology ,Protein Transport ,HEK293 Cells ,src-Family Kinases ,PNAS Plus ,chemistry ,Cancer research ,biology.protein ,Female ,Goblet Cells ,Chemokines ,Cell Adhesion Molecules ,Tyrosine kinase ,Protein Binding - Abstract
Intestinal epithelial cells contribute to regulation of intestinal immunity in mammals, but the detailed molecular mechanisms of such regulation have remained largely unknown. Stomach-cancer-associated protein tyrosine phosphatase 1 (SAP-1, also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10-deficient mice, a model of inflammatory bowel disease, resulted in a marked increase in the severity of colitis in association with up-regulation of mRNAs for various cytokines and chemokines in the colon. Tyrosine phosphorylation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific transmembrane protein of the Ig superfamily, was greatly increased in the intestinal epithelium of the SAP-1-deficient animals, suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in cultured cells through the activation of nuclear factor-κB (NF-κB). In addition, SAP-1 and CEACAM20 were found to form a complex through interaction of their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through which the intestinal epithelium contributes to intestinal immunity.
- Published
- 2015
227. Electrolyte depletion syndrome (McKittrick-Wheelock syndrome) successfully treated by endoscopic submucosal dissection
- Author
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Tetsuya Yoshizaki, Daisuke Watanabe, Yoshiko Ohara, Takashi Toyonaga, Tsukasa Ishida, Shinwa Tanaka, Yoshinori Morita, Eiji Umegaki, Takeshi Azuma, Tatsuya Okuno, Nobunao Ikehara, Hiroshi Yokozaki, Namiko Hoshi, Fumiaki Kawara, and Soichiro Adachi
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Hypochloremia ,Water-Electrolyte Imbalance ,Rectum ,Colonoscopy ,Adenocarcinoma ,Intestinal mucosa ,medicine ,Humans ,Intestinal Mucosa ,Colectomy ,Aged ,medicine.diagnostic_test ,business.industry ,Rectal Neoplasms ,Standard treatment ,Dissection ,Gastroenterology ,General Medicine ,Syndrome ,medicine.disease ,Colorectal surgery ,Surgery ,medicine.anatomical_structure ,Balloon dilation ,Female ,business - Abstract
A 66-year-old woman presented to us with malaise, anorexia and rectal mucous discharge, and her laboratory data showed severe hyponatremia, hypokalemia, hypochloremia and renal failure. Computed tomography revealed massive occupation of the rectum by a large tumor. Colonoscopy revealed a mucus-rich villous tumor in the rectum. As there were no other factors that could cause an electrolyte disorder, she was diagnosed with McKittrick-Wheelock syndrome (MWS). The current standard treatment for MWS is partial surgical colectomy. However, surgeries are invasive and postoperative complications sometimes become an issue. After confirming no signs of submucosal invasion of the tumor by magnifying chromoendoscopic examination, endoscopic submucosal dissection (ESD) was indicated. The tumor was completely removed en bloc without adverse events. The histology showed a mucosal adenocarcinoma containing a villous component, 24.5 x 17.0 cm in size. This removal dramatically improved the patient's symptoms and the electrolyte abnormalities without medication. Although several sessions of endoscopic balloon dilation were required to treat postoperative stricture, she has been symptom-free and had no recurrence for 4 years after treatment. We experienced a case of MWS treated by ESD instead of surgery. ESD should be feasible and beneficial for the treatment of MWS.
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- 2015
228. Measurement of sterilization ability and reactive species of various gas plasma bubbled-up water
- Author
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Hidekazu Miyahara, Toshihiro Takamatsu, Akitoshi Okino, Takeshi Azuma, Yuriko Matsumura, Takaya Oshita, Tetsu Kamiya, Hiroki Matsubara, Satoru Oshima, Yosuke Watanabe, Atsuo Iwasawa, and Tomohiro Kobayashi
- Subjects
chemistry.chemical_compound ,Argon ,chemistry ,Singlet oxygen ,Radiochemistry ,Gas plasma ,chemistry.chemical_element ,Hydroxyl radical ,Plasma ,Irradiation ,Sterilization (microbiology) ,Helium - Abstract
Recently, various sterilization methods using atmospheric non-thermal plasma have been studied. Plasma generates reactive species that contributes to the sterilization. Most of the previous studies were reported that water treated by plasma irradiation (plasma treated water) shows sterilization ability. In these experiments, plasma is irradiated to the water surface from above. Therefore, this method is inefficient because the contact area between the plasma and the water is limited. Additionally, a lot of reactive species such as hydroxyl radical (HO·), singlet oxygen (1O 2 ) are not generated by helium or argon plasma.
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- 2015
229. Investigation of bacterial inactivation by various gas plasmas and electron microscopic observation of treated bacteria
- Author
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Akitoshi Okino, Hidekazu Miyahara, Atsuo Iwasawa, Yuriko Matsumura, Yota Sasaki, Hiroaki Kawano, Yosuke Watanabe, Takeshi Azuma, Toshihiro Takamatsu, and Tomohiro Kobayashi
- Subjects
Materials science ,biology ,Scanning electron microscope ,Microorganism ,fungi ,food and beverages ,chemistry.chemical_element ,Plasma ,Photochemistry ,biology.organism_classification ,Nitrogen ,law.invention ,chemistry.chemical_compound ,chemistry ,law ,Carbon dioxide ,Electron microscope ,Atomic physics ,Electron microscopic ,Bacteria - Abstract
Our group succeeded in developing a multi-gas plasma jet, which can generate plasma from various gas species. Using this plasma source, reactive species can be investigated in detail, since they can be generated selectively by the supplied gas species. This study aims to investigate the amount of reactive species generated by various gas plasmas, find reactive species that can inactivate bacteria and observe treated bacteria using electron microscope.
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- 2015
230. Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics
- Author
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Yoshitake Hayashi, Takeshi Azuma, and Yoshihiko Yano
- Subjects
Hepatitis B virus ,Antigenicity ,Hepatology ,business.industry ,virus diseases ,Minireviews ,Viral quasispecies ,medicine.disease_cause ,medicine.disease ,Diagnostic tools ,Genome ,Virology ,Reverse transcriptase ,digestive system diseases ,Chronic hepatitis ,medicine ,Liver cancer ,business - Abstract
Hepatitis B virus (HBV) infection is major global issue, because chronic HBV infection is strongly associated with liver cancer. HBV spread worldwide with various mutations and variations. This variability, called quasispecies, is derived from no proof-reading capacity of viral reverse transcriptase. So far, thousands of studies reported that the variety of genome is closely related to the geographic distribution and clinical characteristics. Recent technological advances including capillary sequencer and next generation sequencer have made in easier to analyze mutations. The variety of HBV genome is related to not only antigenicity of HBs-antigen but also resistance to antiviral therapies. Understanding of these variations is important for the development of diagnostic tools and the appropriate therapy for chronic hepatitis B. In this review, recent publications in relation to HBV mutations and variations are updated and summarized.
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- 2015
231. Serum level of taurine would be associated with the amelioration of minimal hepatic encephalopathy in cirrhotic patients
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Masaya Saito, Hirotaka Hirano, Kenji Momose, Takeshi Azuma, Masaru Yoshida, and Yoshihiko Yano
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medicine.medical_specialty ,Taurine ,Hepatology ,business.industry ,medicine.disease ,Logistic regression ,University hospital ,Gastroenterology ,Confidence interval ,Surgery ,Predictive factor ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Infectious Diseases ,chemistry ,Treatment modality ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Prospective cohort study ,business ,human activities ,Hepatic encephalopathy - Abstract
Aim A variety of treatment modalities including L-carnitine have been tried for cirrhotic patients with minimal hepatic encephalopathy (MHE), which improved MHE for some patients, but were not effective for the other patients. We aimed to identify pre-therapeutic independent factors to predict the amelioration of MHE after L-carnitine treatment. Methods We performed a prospective cohort study on a total of 64 consecutive outpatients of cirrhotic patients who underwent blood biochemical examinations and neuropsychiatric (NP) test at Kobe University Hospital. MHE patients diagnosed by the NP test were p.o. administrated L-carnitine for 3 months. The patients with and without MHE amelioration were compared, and the independent factors were statistically examined. Predictive scoring systems of the amelioration of MHE were established using multivariate logistic regression. Results The amelioration of MHE was found in 45.8% of MHE patients. Serum taurine before the treatment was the best predictive factor of the amelioration of MHE (P = 0.046). The predictive model using serum taurine discriminated well between patients with and without the amelioration of MHE (area under the receiver–operator curve, 0.748; 95% confidence interval, 0.531–0.901). The predictive scores of the amelioration of MHE enable the patient-specific probability to be easily looked up. Conclusion Serum taurine before L-carnitine treatment was shown to be an independent factor associated with the amelioration of MHE 3 months after the treatment. The easy pre-therapeutic prediction of MHE amelioration after L-carnitine treatment would help in improving awareness of the selection of MHE patients with good response to L-carnitine, thus being beneficial from a financial perspective.
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- 2015
232. [Diagnosis and management for gallbladder polyps]
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Yoshifumi, Arisaka, Mamoru, Takenaka, Hideyuki, Shiomi, and Takeshi, Azuma
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Early Diagnosis ,Polyps ,Time Factors ,Humans ,Gallbladder Neoplasms ,Gallbladder Diseases ,Follow-Up Studies - Published
- 2015
233. Serum NX-DCP as a New Noninvasive Model to Predict Significant Liver Fibrosis in Chronic Hepatitis C
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Hirotaka Hirano, Takeshi Azuma, Masaru Yoshida, Yoshihiko Yano, Kenji Momose, and Masaya Saito
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Pathology ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,medicine.diagnostic_test ,business.industry ,Biopsy ,Liver fibrosis ,des-Gamma-Carboxy Prothrombin ,Fibrosis stage ,Hepatitis C ,medicine.disease ,Gastroenterology ,Kowsar ,Infectious Diseases ,Chronic hepatitis ,Fibrosis ,Internal medicine ,medicine ,Liver Fibrosis ,Chronic ,business ,Research Article - Abstract
Background: Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important. Objectives: We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease. Patients and Methods: We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed. Results: Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05). Conclusions: NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis.
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- 2015
234. Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma
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Masaru Yoshida, Tomohisa Hattori, Katsuya Ohbuchi, Naoki Fujitsuka, Takeshi Azuma, Shin Nishiumi, Akio Inui, and Masahiro Yamamoto
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Article Subject ,business.industry ,Kampo ,Inflammation ,lcsh:Other systems of medicine ,Pharmacology ,medicine.disease ,Systemic inflammation ,lcsh:RZ201-999 ,behavioral disciplines and activities ,Muscle atrophy ,Cachexia ,Complementary and alternative medicine ,Weight loss ,Immunology ,Metabolome ,Medicine ,Ghrelin ,medicine.symptom ,business ,Research Article - Abstract
Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT), a Japanese traditional herbal medicine (Kampo), ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition ofβ-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ(IFN-γ) in tumor-bearing rats and was also found to suppress LPS-induced IFN-γexpression in splenocytesin vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma.
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- 2015
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235. Microbial Inactivation in the Liquid Phase Induced by Multigas Plasma Jet
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Atsuo Iwasawa, Kodai Uehara, Yuriko Matsumura, Masahiro Kohno, Yota Sasaki, Toshihiro Takamatsu, Akitoshi Okino, Takeshi Azuma, Norihiko Ito, and Miyahara Hidekazu
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Plasma Gases ,Radical ,Microorganism ,lcsh:Medicine ,chemistry.chemical_element ,Photochemistry ,Oxygen ,Microbiology ,chemistry.chemical_compound ,Species Specificity ,Drug Interactions ,lcsh:Science ,Spores, Bacterial ,Microbial Viability ,Multidisciplinary ,biology ,Singlet oxygen ,lcsh:R ,Correction ,Free Radical Scavengers ,Sterilization (microbiology) ,biology.organism_classification ,Nitrogen ,chemistry ,Carbon dioxide ,lcsh:Q ,Bacteria ,Research Article - Abstract
Various gas atmospheric nonthermal plasmas were generated using a multigas plasma jet to treat microbial suspensions. Results indicated that carbon dioxide and nitrogen plasma had high sterilization effects. Carbon dioxide plasma, which generated the greatest amount of singlet oxygen than other gas plasmas, killed general bacteria and some fungi. On the other hand, nitrogen plasma, which generated the largest amount of OH radical, killed ≥ 6 log of 11 species of microorganisms, including general bacteria, fungi, acid-fast bacteria, spores, and viruses in 1-15 min. To identify reactive species responsible for bacterial inactivation, antioxidants were added to bacterial suspensions, which revealed that singlet oxygen and OH radicals had greatest inactivation effects.
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- 2015
236. Downregulation of CXCR4 in Metastasized Breast Cancer Cells and Implication in Their Dormancy
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Yuki Ueda, Akihiro Minami, Kenji Momose, Takeshi Azuma, Kentaro Nobutani, Kohta Miyawaki, Yohei Shimono, Kiyohito Mizutani, Toshihiro Suzuki, Koichi Akashi, Yoshimi Takai, and Midori Kitayama
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Pathology ,medicine.medical_specialty ,Receptors, CXCR4 ,Down-Regulation ,lcsh:Medicine ,Breast Neoplasms ,Biology ,CXCR4 ,Metastasis ,Mice ,Breast cancer ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,lcsh:Science ,Multidisciplinary ,CXCR4 antagonist ,Cell Cycle ,lcsh:R ,Cancer ,medicine.disease ,Chemokine CXCL12 ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,Cancer cell ,lcsh:Q ,Cancer dormancy ,Research Article ,Signal Transduction - Abstract
Our understanding of the mechanism of cancer dormancy is emerging, but the underlying mechanisms are not fully understood. Here we analyzed mouse xenograft tumors derived from human breast cancer tissue and the human breast cancer cell line MDA-MB-231 to identify the molecules associated with cancer dormancy. In immunohistological examination using the proliferation marker Ki-67, the tumors included both proliferating and dormant cancer cells, but the number of dormant cells was remarkably increased when they metastasized to the lung. In the gene expression analysis of the orthotopic cancer cells by a single-cell multiplex real-time quantitative reverse transcription PCR followed by flow cytometric analysis, restrained cellular proliferation was associated with downregulation of the chemokine receptor CXCR4. In the immunohistological and flow cytometric analyses, the expression level of CXCR4 in the metastasized cancer cells was decreased compared with that in the cancer cells in orthotopic tumors, although the expression level of the CXCR4 ligand CXCL12 was not reduced in the lung. In addition, the proliferation of the metastasized cancer cells was further decreased by the CXCR4 antagonist administration. In the ex vivo culture of the metastasized cancer cells, the expression level of CXCR4 was increased, and in the xenotransplantation of ex vivo cultured cancer cells, the expression level of CXCR4 was again decreased in the metastasized cancer cells in the lung. These findings indicate that CXCR4 is downregulated in metastasized breast cancer cells and implicated in their dormancy.
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- 2015
237. IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity
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Timothy T. Kuo, Wayne I. Lencer, Masaru Yoshida, Richard S. Blumberg, Kanna Kobayashi, Tetsuya Takagawa, Atsuhiro Masuda, Steven M. Claypool, Takeshi Azuma, and Hiromu Kutsumi
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Lamina propria ,Mucous Membrane ,Immunology ,Dendritic Cells ,General Medicine ,Biology ,Immune complex ,Immune system ,medicine.anatomical_structure ,Neonatal Fc receptor ,Transcytosis ,Antigen ,Immunoglobulin G ,Immunopathology ,medicine ,Humans ,Secretion ,Antigens ,Immunity, Mucosal - Abstract
Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with systemic immune compartments and, as such, provides essential host defense and immunoregulatory functions at the mucosal surfaces.
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- 2006
238. Structural Basis and Functional Consequence of Helicobacter pylori CagA Multimerization in Cells
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Takeshi Azuma, Hideaki Higashi, Shumei Ren, Huaisheng Lu, and Masanori Hatakeyama
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Repetitive Sequences, Amino Acid ,Amino Acid Motifs ,Genetic Vectors ,Molecular Sequence Data ,Protein tyrosine phosphatase ,Biology ,Transfection ,digestive system ,Biochemistry ,Conserved sequence ,src Homology Domains ,Gene product ,chemistry.chemical_compound ,Bacterial Proteins ,Chlorocebus aethiops ,Animals ,CagA ,Amino Acid Sequence ,Phosphorylation ,Molecular Biology ,Peptide sequence ,Conserved Sequence ,Antigens, Bacterial ,COS cells ,Helicobacter pylori ,Tyrosine phosphorylation ,Cell Biology ,Protein-Tyrosine Kinases ,bacterial infections and mycoses ,Molecular biology ,digestive system diseases ,src-Family Kinases ,chemistry ,Genes, Bacterial ,COS Cells ,Mutation ,bacteria ,Protein Tyrosine Phosphatases - Abstract
Helicobacter pylori cagA-positive strains are associated with gastric adenocarcinoma. The cagA gene product CagA is delivered into gastric epithelial cells where it localizes to the plasma membrane and undergoes tyrosine phosphorylation at the EPIYA-repeat region, which contains the EPIYA-A segment, EPIYA-B segment, and Western CagA-specific EPIYA-C or East Asian CagA-specific EPIYA-D segment. In host cells, CagA specifically binds to and deregulates SHP-2 phosphatase via the tyrosine-phosphorylated EPIYA-C or EPIYA-D segment, thereby inducing an elongated cell shape known as the hummingbird phenotype. In this study, we found that CagA multimerizes in cells in a manner independent of its tyrosine phosphorylation. Using a series of CagA mutants, we identified a conserved amino acid sequence motif (FPLXRXXXVXDLSKVG), which mediates CagA multimerization, within the EPIYA-C segment as well as in a sequence that located immediately downstream of the EPIYA-C or EPIYA-D segment. We also found that a phosphorylation-resistant CagA, which multimerizes but cannot bind SHP-2, inhibits the wild-type CagA-SHP-2 complex formation and abolishes induction of the hummingbird phenotype. Thus, SHP-2 binds to a preformed and tyrosinephosphorylated CagA multimer via its two Src homology 2 domains. These results, in turn, indicate that CagA multimerization is a prerequisite for CagA-SHP-2 interaction and subsequent deregulation of SHP-2. The present work raises the possibility that inhibition of CagA multimerization abolishes pathophysiological activities of CagA that promote gastric carcinogenesis.
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- 2006
239. Helicobacter pylori eradication prevents the development of gastric cancer - results of a long-term retrospective study in Japan
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Taiji Akamatsu, Y. Sone, S. Okamoto, H. Yamagata, K. Sato, Takeshi Azuma, Masahiro Asaka, T. Urabe, Shuichi Ohara, H. Nomura, K. Yagi, Jun Miwa, K. Suwaki, S. Inatsuchi, Toshiro Kamoshida, Shuichi Terao, Hajime Isomoto, A. Takagi, E. Tomita, Tomoki Inaba, T. Nakamura, Shin Ichi Takahashi, Masako Kato, and D. Shirasaka
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medicine.medical_specialty ,biology ,business.industry ,Incidence (epidemiology) ,Mortality rate ,Cancer ,Retrospective cohort study ,macromolecular substances ,Helicobacter pylori ,medicine.disease ,biology.organism_classification ,Gastroenterology ,Retrospective data ,Internal medicine ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,business - Abstract
Summary Aim This large-scale study was designed to investigate the incidence of gastric cancer after Helicobacter pylori (H. pylori) eradication in Japan. Methods This study was a retrospective multicentre study performed at 23 centres in Japan. Patients in whom H. pylori had been successfully eradicated and those in whom the infection persisted were entered into the study if they had undergone an upper endoscopic examination at least once a year for five consecutive years. The incidence rates of gastric cancer during follow-up were compared between those whose infections had been successfully eradicated and those with persistent H. pylori infection. Results Three-thousand twenty-one patients were enrolled. The median follow-up was 7.7 years for the infected group and 5.9 years for the eradicated group. Gastric cancer developed in 23 (1%) of those in whom H. pylori was successfully eradicated compared with 44 (4%) of those with persistent H. pylori infection (OR = 0.36; 95% CI = 0.22–0.62). Conclusion This large-scale retrospective clinical study in Japan, which has a high mortality rate for gastric cancer, indicates that H. pylori eradication may prevent the development of gastric cancer.
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- 2006
240. Hypoxia-inducible factor-1 alpha and vascular endothelial growth factor expression in ischaemic colitis and ulcerative colitis
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Yoshiyuki Ito, Takeshi Azuma, Soshoku Lee, Atsushi Muramatsu, T. Inagaki, Yukinao Yamazaki, Shigeji Ito, Ryuho Masaki, Masaru Kuriyama, Hiroyuki Suto, Masahiro Ohtani, Satoko Satomi, Tomoyuki Okuda, and Shinsuke Matsunaga
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Angiogenesis ,Growth factor ,medicine.medical_treatment ,Ischemia ,medicine.disease ,Ulcerative colitis ,Vascular endothelial growth factor ,chemistry.chemical_compound ,Hypoxia-Inducible Factor 1-Alpha ,chemistry ,Biopsy ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Colitis ,business - Abstract
Summary Background Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a transcriptional factor induced by ischaemic crisis in many tissues. Vascular endothelial growth factor (VEGF) is an important growth factor that plays a major role in angiogenesis. Aim We examined the aetiology and pathophysiology of human ischaemic colitis and ulcerative colitis from the viewpoint of the expression of these two ischaemic factors. Methods Thirty-two patients with ischaemic colitis, 16 with ulcerative colitis and 25 normal controls underwent colonoscopy. Biopsy samples were taken from a colitis lesion and a normal region in the same patient. In the normal controls, four biopsy samples were obtained from each subject. Biopsy samples were subjected to real-time polymerase chain reaction. Results Hypoxia-inducible factor and VEGF were overexpressed in ischaemic colitis lesions and quickly decreased to normal levels in the healing phase. In contrast, HIF but not VEGF was overexpressed in active ulcerative colitis lesions. In the remission phase of ulcerative colitis, VEGF decreased to low levels, although HIF was continuously overexpressed. Conclusions Overexpression of HIF and VEGF contribute to the tolerance of ischaemia in patients with active ischaemic colitis. The inconsistency in their expression might be associated with the chronic intestinal damage characteristic of ulcerative colitis.
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- 2006
241. Influence of EPIYA-Repeat Polymorphism on the Phosphorylation-Dependent Biological Activity of Helicobacter pylori CagA
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Kazunori Onoé, Takeshi Yamazaki, Shiho Yamazaki, Masanori Hatakeyama, Hideaki Higashi, Takeshi Azuma, Masanori Naito, and Ryouhei Tsutsumi
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Repetitive Sequences, Amino Acid ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Protein tyrosine phosphatase ,digestive system ,Cell Line ,CSK Tyrosine-Protein Kinase ,chemistry.chemical_compound ,Bacterial Proteins ,Humans ,CagA ,Src family kinase ,Phosphorylation ,Antigens, Bacterial ,Polymorphism, Genetic ,Hepatology ,biology ,Kinase ,Intracellular Signaling Peptides and Proteins ,Gastroenterology ,Tyrosine phosphorylation ,Protein-Tyrosine Kinases ,Helicobacter pylori ,bacterial infections and mycoses ,biology.organism_classification ,Molecular biology ,digestive system diseases ,Phenotype ,src-Family Kinases ,chemistry ,Cancer research ,Tyrosine ,bacteria ,Protein Tyrosine Phosphatases ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Background & Aims: Helicobacter pylori CagA-positive strain is associated with gastric adenocarcinoma. CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation at the EPIYA sites by Src family kinases (SFKs). Owing to homologous recombination within the 3′-region of the cagA gene, 4 distinct EPIYA sites, each of which is defined by surrounding sequences, are variably assembled in both number and order among CagA proteins from different clinical H pylori isolates. Tyrosine-phosphorylated CagA specifically binds and deregulates SHP-2 via the Western CagA-specific EPIYA-C or East Asian CagA-specific EPIYA-D site, and C-terminal Src kinase (Csk) via the EPIYA-A or EPIYA-B site. Here we investigated the influence of EPIYA-repeat polymorphism on the CagA activity. Methods: A series of EPIYA-repeat variants of CagA were expressed in AGS gastric epithelial cells and the ability of individual CagA to bind SHP-2 or Csk was determined by the sequential immunoprecipitation and immunoblotting method. Results: CagA proteins carrying multiple EPIYA-C or EPIYA-D sites bound and deregulated SHP-2 more strongly than those having a single EPIYA-C or EPIYA-D. Furthermore, the ability of CagA to bind Csk was correlated with the number of EPIYA-A and EPIYA-B sites. Because Csk inhibits SFK, CagA with greater Csk-binding activity more strongly inhibited Src-dependent CagA phosphorylation and more effectively attenuated induction of cell elongation caused by CagA–SHP-2 interaction. Conclusions: EPIYA-repeat polymorphism of CagA greatly influences the magnitude and duration of phosphorylation-dependent CagA activity, which may determine the potential of individual CagA as a bacterial virulence factor that directs gastric carcinogenesis.
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- 2006
242. Identification of Lipid Species Linked to the Progression of Non-Alcoholic Fatty Liver Disease
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Takeshi Azuma, Shin Nishiumi, Yuki Kawano, Yoshihiko Yano, Masaya Saito, and Masaru Yoshida
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medicine.medical_specialty ,Cirrhosis ,Clinical Biochemistry ,Glycerophospholipids ,Biology ,digestive system ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Lipid droplet ,Internal medicine ,Drug Discovery ,medicine ,Humans ,Triglycerides ,Diacylglycerol kinase ,Pharmacology ,Fatty liver ,Fatty Acids ,nutritional and metabolic diseases ,medicine.disease ,Lipid Metabolism ,Sphingolipid ,Lipids ,digestive system diseases ,Sterols ,Endocrinology ,Biochemistry ,Liver ,Hepatic stellate cell ,Disease Progression ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Steatohepatitis ,Glycolipids - Abstract
Non-alcoholic fatty liver disease (NAFLD) is histologically characterized by the aberrant accumulation of lipid droplets in the liver, which is positively correlated with insulin resistance. Within the spectrum of this disease, patients can develop hepatitis and cirrhosis; i.e., non-alcoholic steatohepatitis (NASH). The mechanisms responsible for the progression of NAFLD are not fully understood. Triacylglycerol (TAG), which is mainly found in lipid droplets, is currently considered to act as a buffer against the accumulation of non-TAG toxic lipid species. In line with this, recent studies have revealed that insulin resistance is driven by the accumulation of phosphatidic acid and diacylglycerol in hepatocytes and that cholesterol-overloaded stellate cells are associated with fibrosis in the liver. Therefore, it is important to identify the toxic lipid species that contribute to NAFLD progression in order to clarify the pathogenesis of NASH and find novel targets for its treatment. In this review, we divided lipids into five classes; i.e., into fatty acyls, glycerophospholipids, glycerolipids, sphingolipids, and sterol lipids, and described their molecular structures, distributions, and metabolism under physiological conditions, as well as the contributions they make to the progression of NAFLD.
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- 2014
243. Comparison of teprenone and famotidine against gastroduodenal mucosal damage in patients taking low-dose aspirin
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Toshihisa, Takeuchi, Kazuhiro, Ota, Satoshi, Harada, Yuichi, Kojima, Takuya, Inoue, Ryuichi, Iwakiri, Yasuhisa, Sakata, Kazuma, Fujimoto, Tsuyoshi, Fujita, Takeshi, Azuma, and Kazuhide, Higuchi
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Male ,Peptic Ulcer ,Treatment Outcome ,Aspirin ,Histamine H2 Antagonists ,Humans ,Female ,Prospective Studies ,Diterpenes ,Middle Aged ,Anti-Ulcer Agents ,Famotidine ,Aged - Abstract
Proton-pump inhibitors are known to be effective in the treatment and prevention of ulcers related to low-dose aspirin (LDA), but few reports address H2 -receptor antagonists (H2RAs) and gastroprotective agents (GPs). This study was intended to compare the therapeutic effects of an H2RA and a GP against gastroduodenal mucosal injuries in patients taking LDA.The subjects consisted of patients requiring continuous LDA treatment, in whom no peptic ulcer was found on endoscopy at enrollment. The patients were randomized to either famotidine 20 mg/day (group F) or teprenone 150 mg/day (group T). The study medication was administered for 12 weeks. The patients underwent endoscopy after administration of the study medication in order to obtain a Lanza score.A total of 66 patients (38 in group F, 28 in group T) were included in the efficacy analysis population. The Lanza score changed as follows: in group F, it improved significantly, from 0.89±1.03 (mean±standard deviation) before medication to 0.39±0.75 after medication (P=0.006); in group T, no significant difference was observed: 0.75±0.93 before medication and 0.68±0.82 after medication.Famotidine is better than teprenone in terms of reducing the number of the erosions under use of LDA.
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- 2014
244. Efficacy of endoscopic submucosal dissection for residual or recurrent superficial colorectal tumors after endoscopic mucosal resection
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Gabriel, Rahmi, Shinwa, Tanaka, Yoshiko, Ohara, Tsukasa, Ishida, Tetsuya, Yoshizaki, Yoshinori, Morita, Takashi, Toyonaga, and Takeshi, Azuma
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Male ,Reoperation ,Neoplasm, Residual ,Dissection ,Middle Aged ,Endoscopy, Gastrointestinal ,Treatment Outcome ,Humans ,Female ,Intestinal Mucosa ,Neoplasm Recurrence, Local ,Colorectal Neoplasms ,Aged ,Retrospective Studies - Abstract
Superficial colorectal tumors can be treated effectively by endoscopic submucosal dissection (ESD). Few data are available on using ESD for residual or recurrent tumors after the first endoscopic resection. This study aimed to evaluate the efficacy of ESD for these lesions.In all, 28 patients with residual or recurrent superficial colorectal tumors were referred to the Kobe University Hospital for ESD. The therapeutic outcomes and the possible factors predictive of procedure difficulties for ESD were analyzed.In total, 27 (96.4%) patients were successfully treated using ESD. There was no related immediate complication. One patient had a delayed perforation which was then treated surgically. En bloc R0 resection was possible in all the patients and curative resection in 26 patients (92.9%). One invasive cancer was treated surgically. More than one previous endoscopic resection was the only significant predictive factor for the difficulty in performing ESD. None of the patients experienced recurrence during a follow-up of 22 months (range 3-41 months).The use of ESD allowed a high rate of en bloc resection for residual or locally recurrent colorectal tumors. Furthermore, these lesions should be treated by ESD as a first-line treatment.
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- 2014
245. Successful treatment of Cronkhite-Canada syndrome using anti-tumor necrosis factor antibody therapy
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Daisuke Watanabe, Michitaka Kohashi, Nobunao Ikehara, Tomoo Yoshie, Emmy Yanagita, Takeshi Azuma, Namiko Hoshi, Makoto Ooi, Takashi Yamasaki, Tomoo Itoh, and Masaru Yoshida
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Male ,medicine.medical_specialty ,Colonoscopy ,Azathioprine ,Gastroenterology ,Intestinal mucosa ,Gastrointestinal Agents ,Internal medicine ,medicine ,Humans ,Hypoalbuminemia ,medicine.diagnostic_test ,business.industry ,Intestinal Polyposis ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Infliximab ,Diarrhea ,Clinical research ,Treatment Outcome ,Immunology ,Cronkhite–Canada syndrome ,medicine.symptom ,business ,medicine.drug - Abstract
Cronkhite–Canada syndrome (CCS) is a rare nonhereditary syndrome characterized by gastrointestinal polyposis and ectodermal changes [1]. Although several treatments, such as steroids, are available, the prognosis is poor, with a 5-year mortality rate of 55% [2]. A 57-year-old man, who suffered from alopecia, anorexia, severe diarrhea, dystrophic nail changes, and pigmentation on the hands, presented to our hospital. Colonoscopy revealed numerous polyps throughout the colon (●" Fig.1a). Gastroscopy and small-bowel series also showed severe gastric and small-bowel polyposis, and histology showed juvenile-like polyps with mild inflammation. On the basis of these findings, the patient was diagnosed with CCS. He was treated with medications including corticosteroids, antiplasmin agents, and azathioprine; however, the symptoms persisted. He developed intussusception 7 years after diagnosis (●" Fig.1b) and underwent ileocecal resection. As he continued to suffer from frequent relapses, with diarrhea and malnutrition with severe hypoalbuminemia, a different therapeutic strategy was needed to control the disease progression. Supported by a single report finding of high levels of tumor necrosis factor alpha (TNF-α) in tissue affected by CCS [3], implying that antiTNF-α therapy could be useful for CCS patients, the patient was administered infliximab at 200mg every 2 weeks. His general condition improved, and colonoscopy performed 20 months after induction of anti-TNF therapy showed complete remission with the disappearance of polyposis (●" Fig.1c). He now receives 200mg of infliximab every 8 weeks, and has been symptom free for 3 years since the initial administration. There is one report that described strong TNF-α expression in intestinal mucosa affected by CCS, implicating the potential usefulness of anti-TNF-α antibody for patients with CCS. However, to the best of our knowledge, this treatment has not been tested until now [3]. Although we could not detect TNF-α expression in the polyps of this patient by immunohistochemistry (●" Fig.2), given the patient’s dramatic response to therapy, it can be assumed that TNF plays an important role in disease development, perhaps upstream of polyp formation. This case indicates that further basic and clinical research is warranted, and that anti-TNF therapy could be an important new strategy for treatment of CCS.
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- 2014
246. Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPα and RPTPβ, by Helicobacter pylori m2VacA
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Yoshiyuki Ito, Yoshito Nishi, Junzo Hisatsune, Jeroen den Hertog, Blanquita B. De Guzman, Joel Moss, Thea van der Wijk, Eiki Yamasaki, Toshiya Hirayama, Akihiro Wada, Masaaki Nakayama, Shiho Yamazaki, Masahiro Ohtani, Takeshi Azuma, and Kinnosuke Yahiro
- Subjects
chemistry.chemical_classification ,biology ,Immunoprecipitation ,Immunology ,Cell ,Protein tyrosine phosphatase ,biology.organism_classification ,Microbiology ,Molecular biology ,Amino acid ,HeLa ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Receptor-Like Protein Tyrosine Phosphatases ,Cell culture ,Virology ,medicine ,Extracellular - Abstract
Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian cell lines. Sequence differences in the middle of VacA molecules define two families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTPalpha, not RPTPbeta, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTPalpha, not RPTPbeta, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPalpha of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTPalpha less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTPalpha from HeLa cells is less than that of the protein from G401 cells, although their extracellular amino acid sequences are virtually identical, with only two amino acid differences noted. Different post-translational modifications of RPTPalpha in HeLa cells may be responsible for the reduced susceptibility to m2VacA.
- Published
- 2005
247. Identification ofHelicobacter pyloriand thecagAgenotype in gastric biopsies using highly sensitive real-time PCR as a new diagnostic tool
- Author
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Shinkan Tokudome, Akiyo Yamakawa, Hideaki Higashi, Masahiro Ohtani, Norio Matsukura, Shiho Yamazaki, Shunji Kato, Takeshi Azuma, Yukinao Yamazaki, Yoshiyuki Ito, Masanori Hatakeyama, and Hiroyuki Suto
- Subjects
Adult ,Male ,Microbiology (medical) ,Biopsy ,Spirillaceae ,Molecular Sequence Data ,Immunology ,Virulence ,Polymerase Chain Reaction ,Sensitivity and Specificity ,digestive system ,Microbiology ,Helicobacter Infections ,law.invention ,Bacterial Proteins ,law ,RNA, Ribosomal, 16S ,Genotype ,Humans ,Immunology and Allergy ,CagA ,Amino Acid Sequence ,Gene ,Polymerase chain reaction ,Aged ,Antigens, Bacterial ,Polymorphism, Genetic ,Base Sequence ,Helicobacter pylori ,biology ,General Medicine ,Middle Aged ,Thailand ,bacterial infections and mycoses ,biology.organism_classification ,Molecular biology ,digestive system diseases ,RNA, Bacterial ,Infectious Diseases ,Real-time polymerase chain reaction ,Gastric Mucosa ,Genes, Bacterial ,bacteria ,Female - Abstract
The CagA protein is one of the virulence factors of Helicobacter pylori, and two major subtypes of CagA have been observed, the Western and East Asian type. CagA is injected from the bacteria into gastric epithelial cells, undergoes tyrosine phosphorylation, and binds to Src homology 2 domain-containing protein-tyrosine phosphatase SHP-2. The East Asian type CagA binds to SHP-2 more strongly than the Western type CagA. Here, we tried to distinguish the CagA type by highly sensitive real-time PCR with the objective of establishing a system to detect H. pylori and CagA subtypes from gastric biopsies. We designed primers and probe sets for Western or East Asian-cagA at Western-specific or East Asian-specific sequence regions, respectively, and H. pylori 16S rRNA. We could detect the H. pylori 16S rRNA gene, Western and East Asian-cagA gene from DNA of gastric biopsies. The sensitivity and specificity for H. pylori infection was 100% in this system. In Thai patients, 87.8% (36/41) were cagA-positive; 26.8% (11/41) were Western-cagA positive and 53.7% (22/41) were East Asian-cagA positive, while 7.3% (3/41) reacted with both types of cagA. These results suggest that this real-time PCR system provides a highly sensitive assessment of CagA type as a new diagnostic tool for the pathogenicity of H. pylori infection.
- Published
- 2005
248. Rare Helicobacter pylori infection as a factor for the very low stomach cancer incidence in Yogyakarta, Indonesia
- Author
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Kiyonori Kuriki, Shinkan Tokudome, Soeripto, Takeshi Azuma, Hideki Ishikawa, Malcolm A.S. Moore, Susumu Akasaka, F.X. Ediati Triningsih, Hiroshi Kosaka, Sadao Suzuki, and Indrawati Ananta
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Helicobacter pylori infection ,Atrophic gastritis ,Gastroenterology ,Helicobacter Infections ,Japan ,Pepsin ,Stomach Neoplasms ,Internal medicine ,Prevalence ,Humans ,Medicine ,Stomach cancer ,Helicobacter pylori ,biology ,business.industry ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Confidence interval ,Oncology ,Indonesia ,Immunoglobulin G ,biology.protein ,Very low risk ,Female ,business ,Helicobacter pylori IgG - Abstract
To elucidate factors associated with the very low risk of gastric neoplasia in Yogyakarta, Indonesia, approximately 1/50 of the level in Japan, we recruited 52 male and 39 female participants from the general populace in the city of Yogyakarta in October 2003. Helicobacter pylori IgG antibodies were found in only 5% (0-13) (95% confidence interval) and 4% (0-9) for Javanese males and females, respectively, and were statistically lower than the 62% (58-65) and 57% (53-60), respectively, in Japanese. Furthermore, positive findings of pepsinogen test were only 0 and 2% (0-6) for males and females, in Yogyakarta, and were again significantly lower than the 23% (22-25) and 22% (20-23), in Japan. The very low incidence of stomach cancer in Yogyakarta may be due to a low prevalence of H. pylori infection and chronic atrophic gastritis.
- Published
- 2005
249. Diversity ofvacAandcagAgenes ofHelicobacter pyloriin Japanese children
- Author
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Takeshi Azuma, K. Iinuma, S. Yamazaki, Seiichi Kato, Akiyo Yamakawa, Takuji Kato, Masahiro Ohtani, S. Fujiwara, T. Minoura, and W. Zhou
- Subjects
Genetic diversity ,Hepatology ,biology ,Gastroenterology ,Chronic gastritis ,Helicobacter pylori ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,digestive system ,Virology ,Asymptomatic ,digestive system diseases ,Antigen ,Genetic variation ,Genotype ,Immunology ,medicine ,bacteria ,CagA ,Pharmacology (medical) ,medicine.symptom - Abstract
Background: Helicobacter pylori infection is generally acquired in childhood and persists as an asymptomatic infection for decades in most infected individuals. Only a minority develops a clinical outcome even in childhood, such as peptic ulcer. It has been reported that H. pylori infection with the type I strain, which expresses the VacA and CagA antigen, is associated with peptic ulcer. Aim: We examined the diversity of vacA and cagA genes in isolates obtained from Japanese paediatric patients with peptic ulcer or chronic gastritis to investigate the relationship between genetic diversity and clinical outcome. Methods: The diversity of vacA and cagA genes was investigated by PCR and sequence analysis in 30 isolates obtained from Japanese paediatric patients with peptic ulcer (eight strains) or chronic gastritis (22 strains). Results: All isolates from Japanese children were cagA-positive strains. Twenty-six strains (86.7%) had East Asian type CagA, and 4 (13.3%) had Western type CagA. The predominant vacA genotype was s1c/m1b (22/30, 73.3%). There was no significant association between the diversity of cagA and vacA genes and clinical outcome. All four children infected with Western CagA strain had a history of overseas travel or residence. Conclusion: The predominant genotype of H. pylori in Japanese children is East Asian CagA and vacA s1c/m1b genotype, regardless of clinical outcome. Japanese H. pylori strains are homogeneously of the East Asian type; however, Western strains can be introduced into Japan concomitant with host movement from foreign countries in childhood.
- Published
- 2004
250. Distinct Diversity of the cag Pathogenicity Island among Helicobacter pylori Strains in Japan
- Author
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Shiho Yamazaki, Takeshi Azuma, Akiyo Yamakawa, Masahiro Ohtani, Hideaki Higashi, Yukinao Yamazaki, Masanori Hatakeyama, Hiroyuki Suto, Yoshihide Keida, Yoshiyuki Ito, and Atsushi Muramatsu
- Subjects
Microbiology (medical) ,congenital, hereditary, and neonatal diseases and abnormalities ,Atrophic gastritis ,Spirillaceae ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Microbiology ,Bacterial Proteins ,Genotype ,medicine ,Humans ,CagA ,Helicobacter ,Phosphorylation ,Phylogeny ,Genetics ,Antigens, Bacterial ,Genetic diversity ,Helicobacter pylori ,biology ,Intracellular Signaling Peptides and Proteins ,Bacteriology ,biology.organism_classification ,medicine.disease ,Pathogenicity island ,Protein Transport ,Protein Tyrosine Phosphatases - Abstract
The severity of Helicobacter pylori -related disease is correlated with the presence of a cag pathogenicity island (PAI). Genetic diversity within the cag PAI may have a modifying effect on the pathogenic potential of the infecting strain. We analyzed the complete cag PAI sequences of 11 representative Japanese strains according to their vacA genotypes and clinical effects and examined the relationship between the diversity of the cag PAI and clinical features. The cag PAI genes were divided into two major groups, a Western and a Japanese group, by phylogenetic analysis based on the entire cag PAI sequences. The predominant Japanese strains formed a Japanese cluster which was different from the cluster formed by Western strains. The diversity of the cag PAI was associated with the vacA and cagA genotypes. All strains with the s1c vacA genotype were in the Japanese cluster. In addition, all strains with the East Asian-type cagA genotype were also in the Japanese cluster. Patients infected with the Japanese-cluster strain had high-grade gastric mucosal atrophy. These results suggest that a distinct diversity of the cag PAI of H. pylori is present among Japanese strains and that this diversity may be involved in the development of atrophic gastritis and may increase the risk for gastric cancer.
- Published
- 2004
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