Takeshi Azuma

Kobe University, Kōbe, Hyōgo, Japan

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Publications (370)1663.18 Total impact

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    ABSTRACT: A case in which a self-expandable biodegradable (BD) esophageal stent was used for a refractory esophageal anastomotic stricture (EAS) in a 5-year-old female is presented. The patient underwent closure of a tracheoesophageal fistula and gastrostomy in the neonatal period. Esophagoesophagostomy was performed at 18 months of age after a multistaged extrathoracic esophageal elongation procedure. The patient developed refractory EAS and required repeated esophageal balloon dilation. Four sessions of esophageal BD stenting were performed from the age of 5-8 years. Each BD stenting allowed her to eat chopped food, but the anastomotic stricture recurred 4-7 months after the procedure. No major complications were observed, though transient chest pain and dysphagia were observed after each stenting. Finally, at 8 years of age, EAS resection and esophagoesophageal anastomosis were performed. The resected specimens showed thickened scar formation at the EAS lesion, while the degree of esophageal wall damage, both at the proximal and distal ends of the stricture, was slight. To the best of our knowledge, this is the first case report of this kind of treatment and assessment of damage to the esophageal wall microscopically. The advantages and problems of the use of BD stents in children are discussed.
    Clinical journal of gastroenterology. 11/2014;
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    ABSTRACT: Objective Superficial colorectal tumors can be treated effectively by endoscopic submucosal dissection (ESD). Few data are available concerning ESD for residual or recurrent tumors after first endoscopic resection. This study was aimed to evaluate the efficacy of ESD for these lesions.Methods Twenty-eight patients with residual or recurrent colorectal superficial tumors were referred at the Kobe University Hospital for ESD. The therapeutic outcomes and the possible factors predictive of procedure difficulties for ESD were analyzed.ResultsIn total, 27/28 lesions (96%) were successfully treated. There was no related immediate complication. One patient had a delayed perforation treated surgically. En bloc R0 resection was possible in all the patients and curative resection in 26/28 patients (92.8%). One invasive cancer was treated surgically. More than one previous endoscopic resection was the only significant predictive factor for the ESD difficulty. None of the patients experienced recurrence after 22 months (range 3-41) follow-up.Conclusions This study showed that 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 the first-line treatment.
    Journal of Digestive Diseases 11/2014; · 1.85 Impact Factor
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    ABSTRACT: Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):384-392. · 1.89 Impact Factor
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    ABSTRACT: MicroRNA (miRNA) expression profiling has proven useful in diagnosing and understanding the development and progression of several diseases. Microarray is the standard method for analyzing miRNA expression profiles; however, it has several disadvantages, including its limited detection of miRNAs. In recent years, advances in genome sequencing have led to the development of next-generation sequencing (NGS) technologies, which significantly advance genome sequencing speed and discovery. In this study, we compared the expression profiles obtained by next generation sequencing (NGS) with the profiles created using microarray to assess if NGS could produce a more accurate and complete miRNA profile. Total RNA from 14 hepatocellular carcinoma tumors (HCC) and 6 matched non-tumor control tissues were sequenced with Illumina MiSeq 50-bp single-end reads. Micro RNA expression profiles were estimated using miRDeep2 software. As a comparison, miRNA expression profiles for 11 out of 14 HCCs were also established by microarray (Agilent human microRNA microarray). The average total sequencing exceeded 2.2 million reads per sample and of those reads, approximately 57% mapped to the human genome. The average correlation for miRNA expression between microarray and NGS and subtraction were 0.613 and 0.587, respectively, while miRNA expression between technical replicates was 0.976. The diagnostic accuracy of HCC, p-value, and AUC were 90.0%, 7.22610 24 , and 0.92, respectively. In summary, NGS created an miRNA expression profile that was reproducible and comparable to that produced by microarray. Moreover, NGS discovered novel miRNAs that were otherwise undetectable by microarray. We believe that miRNA expression profiling by NGS can be a useful diagnostic tool applicable to multiple fields of medicine. Copyright: ß 2014 Murakami et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report. Competing Interests: The authors declare that they have no competing interests.
    PLoS ONE 09/2014; 9(9):e106314. · 3.53 Impact Factor
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    ABSTRACT: Background/Objectives Many patients with autoimmune pancreatitis (AIP) have an association with diabetes mellitus. It has not been clarified whether steroid therapy for AIP improves or worsens the condition of diabetes mellitus. The aim of this study was thus to investigate the relationship between pancreatic atrophy after steroid therapy and the clinical course of diabetes. Methods Thirty-one AIP patients, who were treated by steroid therapy, were included in this study during December 2005 to March 2013. Pancreatic atrophy 6 months after the beginning of steroid therapy was defined to be present when the width of the pancreatic body was less than 10 mm. The relationships between pancreatic atrophy and patient characteristics as well as the course of diabetes were examined. Results Steroid therapy was effective in all treated patients. Pancreatic atrophy was observed in 12 patients and not in 19 patients after the steroid therapy. AIP patients with pancreatic atrophy showed higher incidences of diabetes mellitus (p=0.001, 9/12 vs. 2/19), diabetes control worsening (p=0.007, 7/12 vs. 2/17), and new onset of diabetes (p=0.02, 5/7 vs. 1/18) than those without atrophy. It was not associated with gender, other organ involvement, pattern of pancreas swelling (diffuse/focal), serum IgG4 level, alcohol intake, and pancreatic calcification on CT. Patients with new onset of diabetes needed insulin therapy, even in the maintenance therapy of AIP. Conclusions AIP patients with pancreatic atrophy after steroid therapy have a high incidence of diabetes mellitus. New onset of diabetes is closely associated with pancreatic atrophy after steroid therapy.
    Pancreatology 09/2014; · 2.04 Impact Factor
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    ABSTRACT: Improvements in analytical technologies have made it possible to rapidly determine the concentrations of thousands of metabolites in any biological sample, which has resulted in metabolome analysis being applied to various types of research, such as clinical, cell biology, and plant/food science studies. The metabolome represents all of the end products and by-products of the numerous complex metabolic pathways operating in a biological system. Thus, metabolome analysis allows one to survey the global changes in an organism's metabolic profile and gain a holistic understanding of the changes that occur in organisms during various biological processes, e.g., during disease development. In clinical metabolomic studies, there is a strong possibility that differences in the metabolic profiles of human specimens reflect disease-specific states. Recently, metabolome analysis of biofluids, e.g., blood, urine, or saliva, has been increasingly used for biomarker discovery and disease diagnosis. Mass spectrometry-based techniques have been extensively used for metabolome analysis because they exhibit high selectivity and sensitivity during the identification and quantification of metabolites. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Furthermore, the findings of studies that attempted to discover biomarkers of gastroenterological cancer are also outlined. Finally, we discuss metabolome analysis-based disease diagnosis
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 09/2014; · 2.78 Impact Factor
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    ABSTRACT: Background & aims To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC. Methods Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used. Results The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (rs = 0.7371, P < 0.0001) in the validation set. Conclusions Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.
    Journal of Crohn s and Colitis 09/2014; · 3.39 Impact Factor
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    ABSTRACT: Endoscopic submucosal dissection (ESD) has been developed for early gastric cancer (EGC). Helicobacter pylori eradication therapy has been reported to have a preventive effect against metachronous recurrence of EGC after ESD. However, the efficacy and safety of eradication therapy on ESD-induced ulcer healing are not clear. In a randomized control study, we compared the standard therapy (8-week proton pump inhibitor) and eradication therapy combined with subsequent treatment with 7-week rebamipide for healing ESD-induced ulcers.
    08/2014;
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    ABSTRACT: Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.Mucosal Immunology advance online publication, 30 July 2014; doi:10.1038/mi.2014.66.
    Mucosal Immunology 07/2014; · 7.54 Impact Factor
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    ABSTRACT: Aims: To investigate the utility of ozone nanobubble water (NBW3) for the treatment of Helicobacter pylori in the stomach, we tested the influence of pepsin concentrations and pH levels on the disinfective activity of NBW3, and the cytotoxicity of NBW3 against mammalian cells and mucosa. Methods: Different concentrations of pepsin were dissolved in NBW3, and the bactericidal activity was tested on H. pylori. NBW3 was adjusted to different pH levels (2.0-7.4) and the bactericidal activity on H. pylori was also tested. To examine the cytotoxicity of NBW3, AGS cells, human gastric epithelial cells, were treated with NBW3 and the viability of the cells was evaluated in vitro. Furthermore, NBW3 was administered to mice and gastric mucosal damage was evaluated by histology. Results: Pepsin reduced the disinfective activity of NBW3 on H. pylori in a pepsin concentration-dependent manner. NBW3 showed stable disinfective activity at all pH levels examined. Cytotoxicity of NBW3 against human gastric epithelial cells and gastric mucosa was not observed in our experimental setting. Conclusions: NBW3 can sustain its disinfective activity in wide range of pH levels and show no cytotoxicity on mammalian cells and tissue. Pepsin can inhibit NBW3 activity in a dose-dependent manner. © 2014 S. Karger AG, Basel.
    Digestion 07/2014; 90(1):10-17. · 1.94 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver disease in developed countries. Non-alcoholic steatohepatitis (NASH), which represents advanced stage NAFLD, is increasingly being recognized as a major cause of liver-related morbidity and mortality. However, no effective drugs against NASH have yet been developed. Therefore, we searched for candidate therapeutic agents based on the changes in levels of hepatic metabolites via gas chromatography mass spectrometry (GC/MS)-based metabolome analysis of livers from methionine-choline deficient (MCD) diet-fed mice, a mouse model of NASH.
    Archives of Biochemistry and Biophysics 05/2014; · 3.37 Impact Factor
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    ABSTRACT: An 85-year-old man underwent endoscopic submucosal dissection (ESD) for a large superficial esophageal epithelial neoplasm, which required removal of 95% of the circumference of the esophageal mucosa. Steroids were administered orally to prevent esophageal stricture starting on day 3 postoperatively. In the 6th week of steroid treatment, he developed high fever without other symptoms. Chest computed tomography (CT) revealed a nodular lesion in the lung. The sputum sample showed gram-positive, branching, filamentous bacteria, and the diagnosis of nocardiosis was suspected. Brain magnetic resonance imaging (MRI) revealed multiple focal lesions, which indicated the dissemination of nocardiosis. Administration of trimethoprim-sulfamethoxazole was immediately started, which led to the disappearance of pulmonary and cerebral nocardiosis with alleviation of fever. Recently, oral steroid treatment has been widely used for the prevention of esophageal stricture. However, our case indicates the risk of life-threatening infection and the importance of close attention with this treatment.
    Digestive Endoscopy 05/2014; · 1.61 Impact Factor
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    ABSTRACT: The development of endoscopic submucosal dissection (ESD) has enabled en bloc resection of lesions regardless of size and shape. However, ESD of colorectal tumors is technically difficult. Early stage colorectal tumors can be removed by endoscopic mucosal resection (EMR) but larger tumors may require piecemeal resection. Therefore, ESD with snaring has been proposed for more reliable EMR and easier ESD. This is a good option to fill the gap between EMR and ESD, and a good step to the introduction of full ESD.
    Gastrointestinal endoscopy clinics of North America 04/2014; 24(2):191-199.
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    ABSTRACT: Helicobacter suis infects the stomachs of both animals and humans, and can induce gastric mucosa-associated lymphoid tissue (MALT) lymphomas. It is known that CXC chemokine ligand 13 (CXCL13) is highly expressed in the Helicobacter-infected mice and gastric MALT lymphoma patients, but the pathway that links the activation of CXCL13 and the formation of gastric MALT lymphomas remains unclear. In this study, we examined whether CXCL13 neutralization would interfere with the formation of gastric lymphoid follicles including B cells, CD4+T cells, dendritic cells (DCs), and follicular DCs (FDCs) in germinal centers to determine the role of CXCL13 in the formation of B-cell aggregates after H. suis infection. Moreover, the expression of genes associated with the lymphoid follicle formation was also effectively suppressed by anti-CXCL13 antibody treatment. These results suggest that the upregulation of CXCL13 has an important role in the development of gastric MALT lymphomas and highlight the potential of anti-CXCL13 antibody for protection against Helicobacter-induced gastric diseases.Mucosal Immunology advance online publication, 19 March 2014; doi:10.1038/mi.2014.14.
    Mucosal Immunology 03/2014; · 7.54 Impact Factor
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    ABSTRACT: Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P<0.05). The prevalence of the V2334I mutation in NS5A was significantly higher in patients who achieved SVR12, while that of G2356E was significantly higher in patients who did not achieve SVR12 (P<0.05). Mutations in the NS3 region that are thought to confer resistance to telaprevir were detected in 3/27 patients who achieved SVR12 (Val36, n=3) and in 5/10 patients who did not achieve SVR12 (Val36, n=4; Thr54, n=1). In conclusion, the IL28B SNP and mutations in the NS5A region were associated with the therapeutic response to triple therapy. Half of the patients who did not achieve SVR12 had mutations conferring resistance to telaprevir. However, pre-existing mutations in NS3 did not affect the efficacy of triple therapy.
    International Journal of Molecular Medicine 03/2014; · 1.96 Impact Factor
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    ABSTRACT: Clarithromycin (CLR) is the key drug in eradication therapy of Helicobacter pylori (H. pylori) infection, and widespread use of CLR has led to an increase in primary CLR-resistant H. pylori. The known mechanism of CLR resistance has been established in A2146G and A2147G mutations in the 23S rRNA gene, but evidence of the involvement of other genetic mechanisms is lacking. Using the MiSeq platform, whole-genome sequencing of the 19 clinical strains and the reference strain ATCC26695 was performed to identify single nucleotide variants (SNVs) of multi-drug resistant efflux pump genes in the CLR-resistant phenotype.
    Gut Pathogens 01/2014; 6:27. · 2.74 Impact Factor
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    ABSTRACT: The study of the omics cascade, which involves comprehensive investigations based on genomics, transcriptomics, proteomics, metabolomics, etc., has developed rapidly and now plays an important role in life science research. Among such analyses, metabolome analysis, in which the concentrations of low molecular weight metabolites are comprehensively analyzed, has rapidly developed along with improvements in analytical technology, and hence, has been applied to a variety of research fields including the clinical, cell biology, and plant/food science fields. The metabolome represents the endpoint of the omics cascade and is also the closest point in the cascade to the phenotype. Moreover, it is affected by variations in not only the expression but also the enzymatic activity of several proteins. Therefore, metabolome analysis can be a useful approach for finding effective diagnostic markers and examining unknown pathological conditions. The number of studies involving metabolome analysis has recently been increasing year-on-year. Here, we describe the findings of studies that used metabolome analysis to attempt to discover biomarker candidates for gastroenterological cancer and discuss metabolome analysis-based disease diagnosis.
    Metabolites. 01/2014; 4(3):547-571.
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    ABSTRACT: The patient was a 15-year-old girl with severe acute hepatitis. A liver biopsy showed the typical findings of autoimmune hepatitis (AIH). Subsequently, two lineages of cytopenia were found in the patient's peripheral blood. Hemophagocytosis by macrophages was observed in the bone marrow. Virus-, drug- and lymphoma-associated hemophagocytic syndrome (HPS) was ruled out. Therefore, the patient was diagnosed with autoimmune-associated HPS (AAHS). Following the administration of combination therapy with prednisolone and cyclosporine A, both the AAHS and AIH improved. This is the first report of AAHS originating from AIH. The patient was followed up for five years after treatment, and no disease recurrence was detected.
    Internal Medicine 01/2014; 53(2):103-7. · 0.97 Impact Factor
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    ABSTRACT: Objective The supplementation of oral branched-chain amino acid (BCAA) granules is known to improve energy metabolism in cirrhotic patients, but not those with hepatocellular carcinoma (HCC). We aimed to clarify whether BCAA granules improve energy metabolism in HCC patients after radiofrequency ablation (RFA). Methods We performed a prospective cohort study (UMIN000004624) involving 40 HCC patients who underwent RFA at Kobe University Hospital. Indirect calorimetry and urinary/blood biochemical examinations were performed before and seven days after RFA. Blood biochemical examinations were also conducted three months after RFA. The patients treated with and without BCAA supplementation were compared, and univariate factors were statistically examined. Results The non-protein respiratory quotient (npRQ) and albumin levels before RFA were significantly lower in the BCAA group than in the control group (p=0.024 and 0.005). The npRQ ratio (seven days after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.019). In addition, the albumin ratio (three months after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.018). Conclusion Supplementation with BCAA granules improves energy metabolism in addition to the liver function after RFA. Improvements in the liver function may result in consistently adequate treatment for HCC recurrence after RFA.
    Internal Medicine 01/2014; 53(14):1469-75. · 0.97 Impact Factor
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    ABSTRACT: Objective: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed. Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated. Results: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively. Conclusions: Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.
    International journal of medical sciences 01/2014; 11(4):321-6. · 2.07 Impact Factor

Publication Stats

7k Citations
1,663.18 Total Impact Points

Institutions

  • 2009–2014
    • Kobe University
      • • Division of Gastroenterology
      • • Department of Agrobioscience
      Kōbe, Hyōgo, Japan
    • Fukui Prefectural University
      Hukui, Fukui, Japan
  • 2013
    • Chiang Mai University
      Amphoe Muang Chiang Mai, Chiang Mai, Thailand
    • Hyogo Cancer Center
      Akasi, Hyōgo, Japan
  • 2011–2013
    • The University of Tokyo
      • • Department of Medical Genome Sciences
      • • Graduate School of Frontier Sciences
      Tokyo, Tokyo-to, Japan
    • Tan Tock Seng Hospital
      Tumasik, Singapore
  • 2010–2013
    • Kobe Gakuin University
      Kōbe, Hyōgo, Japan
  • 2012
    • Kurume University
      • Graduate School of Medicine
      Куруме, Fukuoka, Japan
    • Kobe Pharmaceutical University
      Kōbe, Hyōgo, Japan
  • 2008
    • Kyorin University
      • Department of Internal Medicine
      Edo, Tōkyō, Japan
  • 2005–2008
    • Nagasaki University
      • Department of Bacteriology
      Nagasaki-shi, Nagasaki-ken, Japan
  • 2004–2008
    • University of Fukui
      Hukui, Fukui, Japan
  • 2002–2008
    • Hokkaido University
      • • Graduate School of Science
      • • Institute for Genetic Medicine
      Sapporo-shi, Hokkaido, Japan
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan
    • Fukui General Hospital
      Hukui, Fukui, Japan
  • 1984–2008
    • Kyoto Prefectural University of Medicine
      • Division of Preventive Medicine
      Kioto, Kyōto, Japan
  • 1999–2007
    • Fukui University
      Hukui, Fukui, Japan
  • 2002–2003
    • Tokyo Medical University
      Edo, Tōkyō, Japan
  • 1995–2000
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan
  • 1992
    • Kyoto Prefectural University
      Kioto, Kyōto, Japan
    • University of Texas Southwestern Medical Center
      • Department of Pediatrics
      Dallas, TX, United States
  • 1988–1992
    • Wayne State University
      • School of Medicine
      Detroit, Michigan, United States
  • 1990
    • Detroit Medical Center
      Detroit, Michigan, United States