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Koga, Japan

Fan X.,National Cerebral and Cardiovascular Center | Fan X.,Capital Medical University | Yoshida Y.,Nara Medical University | Honda S.,National Cerebral and Cardiovascular Center | And 23 more authors.
Molecular Immunology | Year: 2013

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Approximately 10% of cases are classified as atypical due to the absence of Shiga toxin-producing bacteria as a trigger. Uncontrolled activation of the complement system plays a role in the pathogenesis of atypical HUS (aHUS). Although many genetic studies on aHUS have been published in recent years, only limited data has been gathered in Asian countries. We analyzed the genetic variants of 6 candidate genes and the gene deletion in complement factor H (CFH) and CFH-related genes, examined the prevalence of CFH autoantibodies and evaluated the genotype-phenotype relationship in 10 Japanese patients with aHUS. We identified 7 causative or potentially causative mutations in CFH (p.R1215Q), C3 (p.R425C, p.S562L, and p.I1157T), membrane cofactor protein (p.Y189D and p.A359V) and thrombomodulin (p.T500M) in 8 out of 10 patients. All 7 of the mutations were heterozygous and four of them were novel. Two patients carried CFH p.R1215Q and 3 other patients carried C3 p.I1157T. One patient had 2 causative mutations in different genes. One patient was a compound heterozygote of the 2 MCP mutations. The patients carrying mutations in CFH or C3 had a high frequency of relapse and a worse prognosis. One patient had CFH autoantibodies. The present study identified the cause of aHUS in 9 out of 10 Japanese patients. Since the phenotype-genotype correlation of aHUS has clinical significance in predicting renal recovery and transplant outcome, a comprehensively accurate assessment of molecular variation would be necessary for the proper management of aHUS patients in Japan. © 2012 Elsevier Ltd. Source

Miyake Y.,Kurashiki University of Science and the Arts | Miyake Y.,Kake Institute of Cytopathology | Aratake Y.,Kurashiki University of Science and the Arts | Aratake Y.,Kake Institute of Cytopathology | And 7 more authors.
Diagnostic Cytopathology | Year: 2012

Tumor cytology has proven to be inadequate for precise diagnosis of thyroid follicular adenoma. This suggests the need for a molecular approach for its diagnosis. Expression of CD26/DPPIV (dipeptidyl peptidas IV), p53, and PTEN was analyzed in smears or sections obtained from 19 patients with histologically proven thyroid follicular adenoma. Papanicolaou staining, CD26/DPPIV activity staining, and HE staining were performed and the specimens were observed morphologically. Immunohistochemical analysis using antibodies against p53 and PTEN was performed. Genetic mutation of PTEN exons was performed using the laser capture microdissection method. The nuclear area of the CD26/DPPIV-positive cells was significantly larger than that of the CD26/DPPIV-negative cells. p53 expression was not observed any specimen. PTEN expression was observed in 18 of 19 cases. DNA sequence analysis did not reveal mutations in exons 5-9 of PTEN in the immunohistochemically PTEN-negative case. In accordance with our previous reports, we found that observation of concomitant CD26-positive and PTEN-negative status in cases of follicular adenoma suggests a state close to follicular carcinoma or progression to cancer, thus warranting careful follow-up. Copyright © 2011 Wiley Periodicals, Inc. Source

Kawagoe J.,University of Miyazaki | Ishikawa T.,University of Miyazaki | Iwakiri H.,Miyakonojo Regional Medical Center | Date H.,Jounan Hospital | And 2 more authors.
International Heart Journal | Year: 2014

Adiponectin has antiatherosclerotic properties and is also produced in the local coronary circulation. We previously reported that signifi cantly less adiponectin was produced in the coronary circulation of patients with than without coronary artery disease (CAD). The goal of this study was to determine whether adiponectin production in the coronary circulation could predict future cardiovascular events in patients with CAD. Forty-eight CAD patients whose left anterior descending coronary arteries required percutaneous coronary intervention (PCI) were enrolled. The amount of adiponectin production in the coronary circulation was defi ned as the plasma adiponectin level at the great cardiac vein minus that at the orifi ce of the left coronary artery. All patients were divided by adiponectin production level in the coronary circulation into the adiponectin-positive production group (> 0 μg/ mL) and adiponectin-negative production group (≤ 0 μg/mL). Median follow-up period was 66 months (maximum, 108 months). The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, heart failure, nonfatal myocardial infarction, revascularization with PCI or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. Sixteen MACE occurred. The incidence of MACE was signifi cantly higher in the adiponectin-negative production group than in the adiponectin-positive production group (P = 0.02). In multivariate analysis, adiponectin-negative production was a predictor of MACE (P = 0.03). Kaplan-Meier analysis revealed that the MACE-free rate was signifi cantly lower in the adiponectin-negative production group than in the adiponectin-positive production group. Adiponectin production in the coronary circulation with CAD may be associated with MACE. Source

Sakamoto S.,University of Miyazaki | Tsuruda T.,University of Miyazaki | Hatakeyama K.,University of Miyazaki | Imamura T.,Koga General Hospital | And 2 more authors.
PLoS ONE | Year: 2014

Background: The adventitia is suggested to contribute to vascular remodeling; however, the site-selective inflammatory responses in association with the development of atherosclerosis remain to be elucidated. Methods and Results: Wild-type or apolipoprotein E knockout male C57BL/6J background mice were fed standard chow for 16, 32, and 52 weeks, and the morphology of the aortic arch, descending aorta, and abdominal aorta was compared. Atheromatous plaque formation progressed with age, particularly in the aortic arch and abdominal aorta but not in the descending aorta. In addition, we found that the numbers of macrophages, T-lymphocytes, and microvessels, assessed by anti-F4/80, CD3, and CD31 antibodies, were higher in the adventitia of the abdominal aorta at 52 weeks. These numbers were positively correlated with plaque formation, but negatively correlated with elastin content, resulting in the enlargement of the total vessel area. In aortic tissues, interleukin-6 levels increased in the atheromatous plaque with age, whereas the level of regulated on activation, normal T cell expressed and secreted (RANTES) increased with age, and compared with other sites, it was particularly distributed in inflammatory cells in the adventitia of the abdominal aorta. Conclusion: This study suggests that adventitial inflammation contributes to the age-dependent structural alterations, and that the activation/inactivation of cytokines/chemokines is involved in the process. © 2014 Sakamoto et al. Source

Inoue Y.,Cancer Institute Hospital | Saiura A.,Cancer Institute Hospital | Yoshioka R.,University of Tokyo | Ono Y.,Cancer Institute Hospital | And 4 more authors.
Annals of Surgery | Year: 2015

Objective: To describe the details of the surgical technique of pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD), using a supracolic anterior artery-first approach. Background: An artery-first approach in PD has been advocated in pancreatic cancer to judge resectability, clear the superior mesenteric artery margin from invasion, or reduce blood loss. However, the efficacy of an artery-first approach in mesopancreas dissection remains unclear. Methods: This study involved 162 consecutive patients who underwent PD with curative intent. The patients were divided into 82 SMD-PDs and 80 conventional PDs (CoPD) and then stratified further according to the dissection level, that is, level 1 was applied to 24 simple mesopancreas divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a hemicircumferential superior mesenteric artery plexus resection to keep the margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results were collected to assess the feasibility and validity of SMDPD with an artery-first approach. Results: Blood loss and operation duration were significantly less in the SMD-PD group than in the CoPD group among the total 162 patients. The imaging analysis showed that four fifths of pancreatic arterial branches came from the right dorsal aspect of the superior mesenteric artery and cancer abutment occurred exclusively from the same direction indicating the validity of an artery-first approach. Conclusions: SMD-PD using an SAA is feasible across PD cases, with acceptable short-term outcomes, and we propose this procedure as a promising option for PD. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

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