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Nakanishi K.,Okinaka Memorial Institute for Medical Research | Saitoh S.,Toranomon Hospital
Diabetes Care

OBJECTIVE - This study clarified characteristics of interferon-associated type 1 diabetes. RESEARCH DESIGNANDMETHODS - The study compared 12 patients with interferon-associated type 1 diabetes with 128 patients with type 1A diabetes with respect to clinical characteristics, and with 10 patients without diabetes despite interferon therapy and 136 normal controlswith respect to HLA allele distributions. RESULTS - Patients with interferon-associated type 1 diabetes retained higher levels of fasting serum C peptide as well as GAD65 antibodies than those with type 1A diabetes until 2 to 4 years after onset. HLA-A*2402 was increased among patientswith interferon-associated type 1 diabetes compared with those without diabetes, despite interferon therapy (odds ratio [OR] 4.00 [95%CI 1.09-17.26]). The haplotype of DRB1*1302- DQA1*0102-DQB1*0604 was increased in these two groups combined compared with normal controls (OR 5.64 [95% CI 2.67-11.81]). CONCLUSIONS - Interferon-associated type 1 diabetes is characterized clinically by high titers of GAD65 antibodies and preserved β-cell function, and genetically by addition of HLA-A* 2402 to DRB1*1302-DQA1*0102- DQB1*0604. © 2011 by the American Diabetes Association. Source

Fujimoto H.,Toranomon Hospital | Kobayashi H.,Okinaka Memorial Institute for Medical Research | Ohno M.,Toranomon Hospital
Circulation Journal

Background: Oxidative stress is thought to play an important role in age-induced atherogenesis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that is localized in mitochondria and protects macrophages against apoptosis induced by oxidized low density lipoprotein (oxLDL). We previously reported that genetic polymorphism of MnSOD modifies mitochondrial MnSOD (mtMnSOD) activity and increases the risk of coronary artery disease. In this study, we investigated the association of mtMnSOD activity with aging. Methods and Results: Blood samples were taken from 69 healthy participants aged 20-52. The MnSOD genotype was analyzed using real-time polymerase chain reaction. Leukocyte mtMnSOD activity was measured by inhibition of WST-1. Macrophages were treated with oxLDL and the apoptotic cells were counted. mtMnSOD activity was inversely correlated with the age of the participant regardless of the MnSOD genotype. The percentage of apoptotic macrophages after incubation with oxLDL correlated with age. Thus, the percentage of apoptotic macrophages after incubation with oxLDL was inversely related to mtMnSOD activity. Lecithinized SOD, which can easily transfer into cells, improved the tolerance of macrophages against oxLDL. Conclusions: mtMnSOD activity decreases with age, thereby reducing the tolerance of macrophages against oxLDL-induced apoptosis. Our data may provide an important clue to clarify the mechanisms of age-induced atherosclerosis. Source

Kaneda H.,Okinaka Memorial Institute for Medical Research | Kaneda H.,Translational Research Informatics Center | Terashima M.,Toyohashi Heart Center | Yamaguchi H.,Tenyoukai Central Hospital
Current Atherosclerosis Reports

New imaging techniques have been used to examine surrogate markers of atherosclerotic burden to determine the effects of pharmacologic intervention. In this review, we discuss the role of intravascular ultrasound (IVUS) in the determination of progression and regression of coronary artery disease. Several methodologic issues are discussed (selection of segments to analyze, measurement error, high drop out rate, and optimal IVUS variables). Usefulness of new IVUS-derived variables (plaque composition by radiofrequency analysis, deformability by palpography, and endothelial shear stress by three-dimensional coronary anatomy reconstructed from IVUS and angiography) will be determined. Based on comparisons between IVUS and clinical studies, IVUS variables seem to be a valid surrogate in studies using atorvastatin in patients with dyslipidemia. It remains unclear whether IVUS variables are valid surrogates for other drugs/diseases. As such, further studies are needed to determine whether IVUS can serve as an efficient surrogate for clinical events in coronary disease trials. © Springer Science+Business Media, LLC 2012. Source

Nakanishi K.,Toranomon Hospital | Nakanishi K.,Okinaka Memorial Institute for Medical Research | Shima Y.,Kyorin University
Diabetes Care

OBJECTIVE - To identify type 1 diabetes-susceptible HLA DR-DQ haplotypes using tag single nucleotide polymorphisms (SNPs) and to estimate the disease risk using these tag SNPs. RESEARCH DESIGN AND METHODS- Five tag SNPs were typed in a total of 211 Japanese subjects including 201 patients with type 1 diabetes who had already been typed for HLA-DRB1, -DQA1, and -DQB1 alleles and 300 control subjects. RESULTS- Tag SNP rs2395185 captured haplotypes involving all DR4 specificities and DR9 specificity with a sensitivity of 98.5% and specificity of 94.9%. Using the T allele of rs2395185, we obtained an odds ratio (95% CI) of 2.87 (2.21-3.74) for type 1 diabetes. In addition, rs3129888 captured haplotypes involving HLA-DRB1*0802 with a sensitivity of 92.3% and specificity of 98.9%. CONCLUSIONS- Typing of two tag SNPs (rs2395185 and rs3129888) may be useful for the screening of Japanese subjects at genetic risk of type 1 diabetes. © 2010 by the American Diabetes Association. Source

Terashima M.,Toyohashi Heart Center | Kaneda H.,Okinaka Memorial Institute for Medical Research | Suzuki T.,Toyohashi Heart Center
Korean Journal of Internal Medicine

Optical coherence tomography (OCT) is an optical analog of intravascular ultrasound (IVUS) that can be used to examine the coronary arteries and has 10-fold higher resolution than IVUS. Based on polarization properties, OCT can differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identify thin-cap fibroatheroma. Because of the strong attenuation of light by blood, OCT systems required the removal of blood during OCT examinations. A recently developed frequency-domain OCT system has a faster frame rate and pullback speed, making the OCT procedure more user-friendly and not requiring proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT can provide detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition [ISA]). At follow-up examinations after stent implantation, stent strut coverage and ISA can be assessed. Several OCT studies have demonstrated delayed neointimal coverage following drug-eluting stent (DES) implantation vs. bare metal stent (BMS) placement. While newer DESs promote more favorable vascular healing, the clinical implications remain unknown. Recent OCT studies have provided insights into restenotic tissue characteristics; DES restenotic morphologies differ from those with BMSs. OCT is a novel, promising imaging modality; with more in-depth assessments of its use, it may impact clinical outcomes in patients with symptomatic coronary artery disease. © 2012 The Korean Association of Internal Medicine. Source

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