The Framingham Risk Score (FRS) has been reported to predict coronary heart disease (CHD), but its assessment has been unsuccessful in Asian population. We aimed to assess FRS and Suita score (a Japanese CHD prediction model) in a Japanese nation-wide annual health check program, participants aged 40-79 years were followed up longitudinally from 2008 to 2011. Of 35,379 participants analyzed, 1,234 had new-onset CHD. New-onset CHD was observed in diabetic men [6.00%], non-diabetic men [3.96%], diabetic women [5.51%], and non-diabetic women [2.86%], respectively. Area under the curve (AUC) of receiver operating characteristic (ROC) curve for CHD prediction were consistently low in Suita score (TC), FRS (TC) and NCEP-ATPIII FRS (TC), suggesting that these scores have only a limited power. ROC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) and Hosmer-Lemeshow goodness-of-fit test did not show clear differences between Suita score (TC) and FRS (TC). New models combining waist circumference ≥85 cm in men or proteinuria ≥1+ in women to Suita score (TC) was superior in diabetic men and women. New models could be useful to predict 3-year risk of CHD at least in Japanese population especially in diabetic population.
Abstract Objective In Japan, while it is known that underweight women over the age of 40 years have a high risk for type 2 diabetes, there is a lack of clarity on the association between glucose tolerance and underweight in younger women. Accordingly, we investigate the prevalence and features of impaired glucose tolerance (IGT) in young underweight Japanese women. Designs and Methods In this cross-sectional study, we recruited 56 normal weight and 98 underweight young Japanese women and evaluated their glucose tolerance levels using an oral glucose tolerance test. Then, we compared the clinical characteristics associated with normal glucose tolerance (NGT) and IGT in the underweight women. Insulin secretion, whole-body insulin sensitivity, and adipose tissue insulin resistance values were measured using the insulinogenic index, whole-body insulin sensitivity index (Matsuda index), and adipose insulin resistance index (Adipo-IR), respectively. Fitness level (peak VO2) was measured using an ergometer. Results The prevalence of IGT was higher in the underweight women than the normal weight women (13.3% vs 1.8%). The underweight women with IGT showed a lower insulinogenic index, lower peak VO2, and Matsuda index and a higher fasting free fatty acid level and Adipo-IR than those with NGT. The whole-body composition was comparable between the NGT and IGT groups. Conclusions The prevalence of IGT was higher in young Japanese women with underweight than those with a normal weight. The underweight women with IGT showed impaired early-phase insulin secretion, low fitness levels, and reduced whole-body and adipose tissue insulin sensitivity levels.
As remarkable improvements have been made to the working environment and working methods of oyster shucking workers during the past 30 years, a study was made on the effects of these improvements on hoya (sea-squirt) asthma and the following results were obtained. 1) The prevalence of hoya (sea-squirt) asthma among oyster shucking workers was 36.0%, 30.1%, 21.7%, 22.0%, 18.0%, and 26.6% in 1963, 1968, 1976, 1984, 1988, and 1992, respectively. Accompanying the improvements made to the working environment and working methods, asthmatic symptoms failed to develop in some of the patients through engaged in oyster shucking work. Thus, those with symptoms actually accounted for 36.0%, 18.7%, 15/8%, 7.4%, 8.4%, and 8.0% of the workers, respectively. 2) The proportion of serious cases among the patients rapidly decreased from 29.2% in 1963 to 0% after 1984. On the other hand the proportion of slight cases was 35.4% in 1963, but after 1988 all the cases were slight cases. 3) During the period from 1984 to 1992, the number of those newly engaged in oyster shucking work was 74. The number of those who developed hoya (sea-squirt) asthma during this period was 8 or 10.1%. All the cases were asthma of the rhinitis type. 4) The number of workers who did not develop asthmatic symptoms though engaged in oyster shucking work was 53 in 1984, 40 in 1988, and 49 in 1992. Of this number, 31% are now under hyposensitization therapy, 57.0% have received this therapy in the past, and 12.0% have not received any therapy.
Lipid infusion and high fat feeding are established causes of systemic and adipose tissue insulin resistance. In this study, we treated 3T3-L1 adipocytes with a mixture of free fatty acids (FFAs) to investigate the molecular mechanisms underlying fat-induced insulin resistance. FFA treatment impaired insulin receptor-mediated signal transduction and decreased insulin-stimulated GLUT4 translocation and glucose transport. FFAs activated the stress/inflammatory kinases c-Jun N-terminal kinase (JNK) and IKKbeta, and the suppressor of cytokine signaling protein 3, increased secretion of the inflammatory cytokine tumor necrosis factor (TNF)-alpha, and decreased secretion of adiponectin into the medium. RNA interference-mediated down-regulation of JNK blocked JNK activation and prevented most of the FFA-induced defects in insulin action. Blockade of TNF-alpha signaling with neutralizing antibodies to TNF-alpha or its receptors or with a dominant negative TNF-alpha peptide had a partial effect to inhibit FFA-induced cellular insulin resistance. We found that JNK activation by FFAs was not inhibited by blocking TNF-alpha signaling, whereas the FFA-induced increase in TNF-alpha secretion was inhibited by RNA interference-mediated JNK knockdown. Together, these results indicate that 1) JNK can be activated by FFAs through TNF-alpha-independent mechanisms, 2) activated JNK is a major contributor to FFA-induced cellular insulin resistance, and 3) TNF-alpha is an autocrine/paracrine downstream effector of activated JNK that can also mediate insulin resistance.
In this study, the simulated simple transplantation system of the neurons differentiated form of mouse iPS (induced pluripotent stem) cells is investigated. Mouse iPS cells are differentiated into neurons by SFEBq method. Two colonies of neuronal cells are prepared, one is the recipient cells and the other is donor cells. At first, suspension culture of recipient cell is started. Then, in 5 days, suspension culture of donor cell is started with recipient cell shifted to adhesion culture. In 10 days, transplantation of donor cell is conducted next to recipient cell. Neuron networks between the recipient cells and the donor cells are jointed for 5 days of culturing. Then, the dynamic stimulation is applied using the 3-D vibration stage to the neuronal networks to promote formation and merging. The total stimulation time is set as 96 hours, that is the vibratory stimulations are applied to the transplantation system during 4 days from one day after transplantation. As a result, it is suggested that the neuron networks are constructed actively with the dynamic stimulation.
A fiberoptic ductoscopy system was successfully developed by means of which we were able to observe the duct cavity of the breast. Two kinds of silicafiberscopes with outer diameters 0.80 and 0.45 mm were used in the present study. Fiberoptic ductoscopy was applied to 52 ducts in 46 patients with nipple discharge for whom no tumor was palpable; the intraductal appearance could be observed in 47 ducts from 41 patients (90.3%). Fourteen ducts from 13 patients were operated upon and were histologically diagnosed as carcinoma (four cases), intraductal papilloma (nine ducts from eight patients) and mastitis (one case). The internal surface of a normal duct was lustrous and smooth. Cancer growing on the surface of a duct wall appeared white and was slightly elevated, forming a bridging structure. The intraductal papillomas formed intraductal solid nodules, being yellow in most cases and red at the site of hemorrhage. Fiberoptic ductoscopy can be used to recognize the growth of minute intraductal lesions in cases of nipple discharge. Clinical endoscopic diagnosis for minute intraductal lesions will make an important contribution to the early detection of cancer and the evaluation of nipple involvement in intraductal carcinoma.
The occurrence of ocular metastasis from lung cancer is uncommon. The present study reports the case of a 69-year-old female patient with lung adenocarcinoma who was found to have a metastatic lesion in the left choroid at the time of presentation. As the patient was found to have a mutation in the epidermal growth factor receptor, treatment with gefitinib was administered; however, the response was evaluated as a progressive disease. Thereafter, the patient received chemotherapy with carboplatin, pemetrexed and bevacizumab. Radiological imaging revealed shrinkage of the primary lesion and choroidal metastasis, and the visual power of the left eye was also shown to improve. Therefore, the present case report demonstrated the efficacy and safety of systemic bevacizumab therapy in combination with a platinum doublet for the treatment of choroid metastasis, with morphological and functional improvements observed with regard to the choroidal metastatic tumor.
