Association of the Trp64Arg Mutation of the β3-Adrenergic Receptor with Diabetes Mellitus, Impaired Glucose Tolerance and Lifestyle in Japanese Workers

In order to investigate whether the Trp64Arg (a missense mutation of tryptophan for arginine at position 64 codon) polymorphism of the β3-adrenergic receptor (β3-AR) gene is related to the incidence of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT), a retrospective cohort study among Japanese workers was conducted. The subjects were Japanese workers at an occupational site in Shimane Prefecture. Informed consent was obtained from 492 workers. The baseline data were obtained at the regular health examination in 1992 and a retrospective cohort study was performed for analyzing the incidence of NIDDM and IGT in 1998. The Trp64Arg polymorphism β3-AR gene for each worker was detected by the single strand conformation polymerase analysis. Relative risks were calculated by the logistic regression analysis. The rates of Trp64Trp (TT), Trp64Arg (TA) and Arg64Arg (AA) genotypes were 66.3%, 31.1% and 2.6%, respectively. The relative risk of (TA + AA) against TT for the incidence of NIDDM and IGT by univariate analysis was 1.37 (95% incidence of NIDDM and IGT adjusted for confounders in a multiple logistic regression model including age, gender, family history, body mass index, alcohol consumption, eating habits and exercise was 1.31 (95% confidence interval, 0.65-2.67). The present findings suggested that a weak association between Trp64Arg polymorphism of the β3-AR gene and the incidence of NIDDM and IGT

A Molecular Variant of the Angiotensinogen Gene and Hypertension in a Case-Control Study in Japanese

In order to examine the distribution of M235T (the substitution of threonine for 0methionine at position 235 codon) polymorphism genotypes of the angiotensinogen (AGT) gene and the relationship between M235T polymorphism of the AGT gene and hypertension, a descriptive study and a case-control study were performed among Japanese workers. The subjects were 2042 workers at an occupational site in Shimane Prefecture in Japan. The database was set up for the workers' regular health examination in 1998. The M235T polymorphism of the AGT gene for each worker was defined by the mutant allele specific amplification (MASA) method. The rates of M235M (MM), M235T (MT) and T235T (TT) genotypes were 3.9%, 30.7% and 65.5%, respectively. The odds ratios of MT and TT against MM for hypertension by univariate analysis were 0.77 [95% confidence interval (CI) 0.27-2.18] and 0.77 (95% CI 0.28-2.14), respectively. The odds ratios of MT and TT against MM for hypertension, adjusted for body mass index, fasting blood sugar, drinking habits, cigarette smoking and exercise in a logistic regression model, were 0.90 (95% CI 0.29-2.74) and 0.87 (95% CI 0.30-2.58), respectively. The data from this study suggests that there may be no relationship between the M235T polymorphism of the AGT gene and hypertension. Further prospective studies are needed to resolve this issue

Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003

Objective To investigate the degree to which ionising radiation confers risk of mortality from heart disease and stroke

Skin Cancer Incidence among Atomic Bomb Survivors from 1958 to 1996

The radiation risk of skin cancer by histological types has been evaluated in the atomic bomb survivors. We examined 80,158 of the 120,321 cohort members who had their radiation dose estimated by the latest dosimetry system (DS02). Potential skin tumors diagnosed from 1958 to 1996 were reviewed by a panel of pathologists, and radiation risk of the first primary skin cancer was analyzed by histological types using a Poisson regression model. A significant excess relative risk (ERR) of basal cell carcinoma (BCC) (n = 123) was estimated at 1 Gy (0.74, 95% confidence interval (CI): 0.26, 1.6) for those age 30 at exposure and age 70 at observation based on a linear-threshold model with a threshold dose of 0.63 Gy (95% CI: 0.32, 0.89) and a slope of 2.0 (95% CI: 0.69, 4.3). The estimated risks were 15, 5.7, 1.3 and 0.9 for age at exposure of 0-9, 10-19, 20-39, over 40 years, respectively, and the risk increased 11% with each one-year decrease in age at exposure. The ERR for squamous cell carcinoma (SCC) in situ (n = 64) using a linear model was estimated as 0.71 (95% CI: 0.063, 1.9). However, there were no significant dose responses for malignant melanoma (n = 10), SCC (n = 114), Paget disease (n = 10) or other skin cancers (n = 15). The significant linear radiation risk for BCC with a threshold at 0.63 Gy suggested that the basal cells of the epidermis had a threshold sensitivity to ionizing radiation, especially for young persons at the time of exposure

Radiation-Induced Esophagitis Exacerbated by Everolimus

Background: Everolimus, a potent mammalian target of rapamycin (mTOR) inhibitor, has shown anticancer activity against various types of cancer, including renal cell carcinoma (RCC); however, little information is available on the efficacy and safety of the combination of everolimus and radiotherapy. We report a case of radiation-induced esophagitis that might have been exacerbated by the sequential administration of everolimus. Case Presentation: A 63-year-old Japanese man with RCC complained of back pain, and magnetic resonance imaging revealed vertebral metastases. He received radiotherapy (30 Gy/10 fractions) to the T6-10 vertebrae. Everolimus was administered immediately after the completion of radiotherapy. One week later, he complained of dysphagia, nausea and vomiting. An endoscopic examination of the esophagus showed erosive esophagitis in the middle to lower portions of his thoracic esophagus, corresponding to the irradiation field. Conclusion: Clinicians should be aware that everolimus might lead to the unexpected exacerbation of radiation toxicities