Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals
Iwata M.,University of Toyama |
Maeda S.,RIKEN |
Kamura Y.,University of Toyama |
Takano A.,Saiseikai Takaoka Hospital |
And 8 more authors.
Diabetes Care | Year: 2012
OBJECTIVE - We evaluated the clinical usefulness of a genetic risk score (GRS) based on 14 well-established variants for type 2 diabetes. RESEARCH DESIGN AND METHODS - We analyzed 14 SNPs at HHEX, CDKAL1, CDKN2B, SLC30A8, KCNJ11, IGF2BP2, PPARG, TCF7L2, FTO, KCNQ1, IRS-1, GCKR, UBE2E2, and C2CD4A/B in 1,487 Japanese individuals (724 patients with type 2 diabetes and 763 control subjects). A GRS was calculated according to the number of risk alleles by counting all 14 SNPs (T-GRS) as well as 11 SNPs related to β-cell function (β-GRS) and then assessing the association between each GRS and the clinical features. RESULTS - Among the 14 SNPs, 4 SNPs were significantly associated with type 2 diabetes in the present Japanese sample (P < 0.0036). The T-GRS was significantly associated with type 2 diabetes (P = 5.9 × 10-21). Among the subjects with type 2 diabetes, the β-GRS was associated with individuals receiving insulin therapy (b = 0.0131, SE = 0.006, P = 0.0431), age at diagnosis (β = 20.608, SE = 0.204, P = 0.0029), fasting serum C-peptide level (β = 20.032, SE = 0.0140, P = 0.022), and C-peptide index (β = 20.031, SE = 0.012, P = 0.0125). CONCLUSIONS - Our data suggest that the β-GRS is associated with reduced β-cell functions and may be useful for selecting patients who should receive more aggressive β-cell-preserving therapy. © 2012 by the American Diabetes Association.
Okada Y.,RIKEN |
Okada Y.,University of Tokyo |
Terao C.,Kyoto University |
Ikari K.,Tokyo Women's Medical University |
And 58 more authors.
Nature Genetics | Year: 2012
Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10 -8, including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves′ disease (P = 3.5 × 10 -4 and 2.9 × 10 -4, respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations. © 2012 Nature America, Inc. All rights reserved.
Kanatani K.T.,University of California at San Diego |
Kanatani K.T.,Kyoto University |
Ito I.,Kyoto University |
Al-Delaimy W.K.,University of California at San Diego |
And 12 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010
Rationale: Desert dust particles, including quartz, which causes inflammatory responses in the airway in animal studies, are transported to widespread regions around the globe. Epidemiologically, areas impacted by desert dust storms, such as communities in the Middle East and the Caribbean, seem to have higher incidences of asthma than might be expected. Objectives: We investigated the magnitude of association between airborne mineral dust concentration and hospitalization of children for asthma exacerbation by using Light Detection And Ranging (LIDAR) with a polarization analyzer for an exposure measurement, which can distinguish mineral dust particles from other particles. Methods: A case-crossover design was used. The exposure measurement was LIDAR's nonspherical extinction coefficient. The outcome measurement was hospitalization of children aged 1 to 15 years for asthma exacerbation in eight principal hospitals in Toyama, a local area in Japan bordering the Japan Sea, during February to April, 2005 to 2009. Measurements and Main Results: During the study period, there were 620 admissions for asthma exacerbation, and 6 days with a heavy dust event (daily mineral dust concentration > 0.1 mg/m 3). Conditional logistic regression showed a statistically significant association between asthma hospitalization and a heavy dust event. The crude odds ratio (OR) of the heavy dust event for hospitalization on the day was 1.88 (95% confidence interval [CI], 1.04-3.41; P = 0.037), and the O Rof heavy dust event during the previous week was 1.83 (95% CI, 1.31-2.56; P = 0.00043). The OR adjusted by other air pollutant levels, pollen, and meteorological factors was 1.71 (95% CI, 1.18-2.48; P = 0.0050). Conclusions: Heavy dust events are associated with an increased risk of hospitalizations for asthma.
Sato T.,University of Toyama |
Kameyama T.,University of Toyama |
Noto T.,Saiseikai Toyama Hospital |
Nakadate T.,Saiseikai Takaoka Hospital |
And 3 more authors.
Journal of Thrombosis and Thrombolysis | Year: 2014
Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6 months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163 > 10 % (CD163high, n = 20) and CD163 ≤ 10 % (CD163low, n = 20). CD163high group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD163high group. In subgroups with the final TIMI-3 flow (CD163high-Reflow, n = 15 and CD163low-Reflow, n = 20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r = -0.49, P = 0.01; systole, r = -0.65, P < 0.01) or %FS (r = 0.51, P < 0.01) at 6 months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion. © 2013 Springer Science+Business Media New York.
PubMed | University of Toyama, Kyowa Hakko Kirin Co, Home Palliative Care Committee, Saiseikai Takaoka Hospital and 2 more.
Type: Journal Article | Journal: The American journal of hospice & palliative care | Year: 2015
To examine the feasibility and usefulness of a novel region-based pathway: the Regional Referral Clinical Pathway for Home-Based Palliative Care.This was a feasibility study to evaluate the frequency of variances and the perceived usefulness of pathway using in-depth interviews. All patients with cancer referred to the palliative care team between 2011 and 2013 and received home care services were enrolled.A total of 44 patients were analyzed, and pathway was completed in all the patients. The target outcome was achieved in 61.4% while some variances occurred in 54.5%. Nine categories were identified as the usefulness of the pathway, such as reviewing and sharing information and promoting communication, education, motivation, and relationships.This novel pathway is feasible and seems to be useful.
PubMed | Seirei Mikatahara Hospital, Home Palliative Care Committee, University of Toyama and Saiseikai Takaoka Hospital
Type: | Journal: BMC palliative care | Year: 2015
Many patients wish to stay at home during the terminal stage of cancer. However, there is concern that medical care provided at home may negatively affect survival. This study therefore explored whether the survival duration differed between cancer patients who received inpatient care and those who received home care.We retrospectively investigated the place of care/death and survival duration of 190 cancer patients after their referral to a palliative care consultation team in a Japanese general hospital between 2007 and 2012. The patients were classified into a hospital care group consisting of those who received palliative care in the hospital until death, and a home care group including patients who received palliative care at home from doctors in collaboration with the palliative care consultation team. Details of the place of care, survival duration, and patient characteristics (primary site, gender, age, history of chemotherapy, and performance status) were obtained from electronic medical records, and analyzed after propensity score matching in the place of care.Median survival adjusted for propensity score was significantly longer in the home care group (67.0days, n=69) than in the hospital care group (33.0days, n=69; P=0.0013). Coxs proportional hazard analysis revealed that the place of care was a significant factor for survival following adjustment for covariates including performance status.This study suggests that the general concern that home care shortens the survival duration of patients is not based on evidence. A cohort study including more known prognostic factors is necessary to confirm the results.
PubMed | University of Toyama, Saiseikai Takaoka Hospital, Kamiichi General Hospital, Asahi General Hospital and 4 more.
Type: Journal Article | Journal: PloS one | Year: 2016
Several studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population.We genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMImax) before or at the time of diagnosis and 693 control individuals with information regarding their BMImax.The BMImax showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMImax and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMImax and age.These results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMImax before or at the time of diagnosis.
Shimada M.,Saiseikai Takaoka Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2013
A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.
Takano A.,Saiseikai Takaoka Hospital |
Niimi H.,University of Toyama |
Atarashi Y.,Toyama Rosai Hospital |
Sawasaki T.,Saiseikai Takaoka Hospital |
And 5 more authors.
Liver International | Year: 2011
Hereditary haemochromatosis (HH), which is mainly associated with a C282Y polymorphism in HFE, is common among Caucasians of north European descent, but is very rare among Asians. Herein, we report a 43-year-old Japanese man who was diagnosed as having HH. A laboratory examination revealed an elevated serum iron level (280 μg/dl), hyperferritinemia (1698 ng/ml) and a low serum level of hepcidin-25 (4.0 ng/ml). Abdominal magnetic resonance imaging revealed findings suggestive of iron accumulation in the liver and pancreas. HFE gene sequencing in the patient revealed a novel homozygous TAC nucleotide deletion (c. 691-693del) responsible for the loss of a tyrosine at position 231 (p. Y231del) of the HFE protein. This homozygous Y231del mutation was recently found in the Huh-7 hepatoma cell line and was shown to prevent the translocation of HFE to the cell surface. This clinical case provides in vivo evidence suggesting that Huh-7 is undoubtedly a human haemochromatotic cell line and, as such, is a valuable tool for investigating the pathogenesis of HFE-related HH in humans. © 2011 John Wiley & Sons A/S.
PubMed | Saiseikai Takaoka Hospital and University of Toyama
Type: Case Reports | Journal: Journal of medical ultrasonics (2001) | Year: 2015
Enterolithiasis is an uncommon finding of a dilated hyperechogenic bowel with multiple ball-like echogenic structures at a routine prenatal check-up using ultrasonography. We here report a case of prenatally diagnosed enterolithiasis at 18 weeks of gestation, showing multiple hyperechogenic foci rolling within the bowel fluid after peristalsis. The size of the dilated bowel gradually increased during pregnancy. Magnetic resonance image demonstrated the dilated lower bowel with blind-ending rectum. A postnatal contrast medium study with retrograde urethrography revealed a middle imperforate anus and a rectourethral fistula. A careful examination, even before 20 weeks of gestation, is extremely useful in demonstrating intraluminal coarse calcifications within an echogenic bowel.