カンキョウ ヨウイン ノ ケンコウ リスク ヒョウカ ト シッペイ ヨボウ エノ コウケン

The research interest of authors has focused on the risk assessment of environmental pollutants such as cadmium and dioxin-related compounds, and epidemiology of human T-cell lymphotropic virus type-I （HTLV-I） infection. The authors （１） showed that low-molecular weight proteinuria and reduced glomerular filtration rate caused by environmental cadmium were strongly associated with shortened survival， （２） clarified serological risk factors for development of adult T-cell leukemia/lymphoma among asymptomatic HTLV-I carriers （plasma levels of soluble interleukin２-receptor＞＝５００U/ml and HTLV-I antibody titer＞＝１，０２４）， （３） conducted the first prospective study of HTLV-I infection and development of malignances other than ATL, and found a significantly reduced risk of gastric cancer among HTLV-I carriers, and （４） by a cooperative study, clarified a new pathogenicity of HTLV-I （association with Sjögren’s syndrome）

Vascular hyperpermeability in severe influenza

Multiorgan failure with vascular hyperpermeability is the final outcome in the progression of seasonal influenza virus pneumonia and influenza-associated encephalopathy, and it is also common in infection with highly pathogenic avian influenza virus. However, the precise molecular mechanism by which influenza virus infection causes vascular endothelial cell hyperpermeability remains poorly defined. We investigated the mechanisms of hyperpermeability of human umbilical vein endothelial cells infected with influenza A virus (IAV)/Puerto Rico/8/34 (PR8) (H1N1). The levels of β-catenin, a key regulatory component of the vascular endothelial-cadherin cell adhesion complex, were markedly decreased during infection for 28 h, with increments of vascular hyperpermeability measured by transendothelial electrical resistance. Lactacystin (at 2 μM), a proteasome inhibitor, inhibited the decrease in β-catenin levels. Since the N-terminal phosphorylation of β-catenin by glycogen synthase kinase (GSK)-3β is the initiation step of proteasome-dependent degradation, we examined the effects of GSK-3β suppression by RNA interference in endothelial cells. IAV-infection-induced β-catenin degradation was significantly inhibited in GSK-3β-knockdown cells, and transfection of cells with recombinant β-catenin significantly suppressed IAV-induced hyperpermeability. These findings suggest that IAV infection induces GSK-3β-mediated β-catenin degradation in the adherens junctional complexes and induces vascular hyperpermeability. The in vitro findings of β-catenin degradation and activation of GSK-3β after IAV infection were confirmed in lungs of mice infected with IAV PR8 during the course of infection from day 0 to day 6. These results suggest that GSK-3β-mediated β-catenin degradation in adherens junctions is one of the key mechanisms of vascular hyperpermeability in severe influenza

トクシマケン ニオケル シインベツ オヨビ アクセイ シュヨウ ゾウキベツ ノ ヒョウジュンカ シボウヒ ノ ブンセキ1993 2002ネン

To clarify the characteristics of mortality in Tokushima Prefecture, the authors analyzed the standardized mortality ratio（SMR）from 1993 to 1998 and 1999 to 2002. The sex-and 5-year-agespecific and cause-specific morality rates in Japan were used as the standard mortality, and the population of sex-and 5-year-age-specific category in the census year（1995 and 2000）was used as the population of Tokushima Prefecture. The 95 % confidence interval（CI）of SMR was estimated using the exact method, on the assumption that the number of deaths followed the Poisson distribution. The mortality from all-cause in Tokushima Prefecture was significantly lower than that of the entire Japanese population among women during 1993-1998, while it was significantly higher among men and women during 1999-2002. The SMRs of diabetes mellitus, bronchitis, emphysema and asthma, and chronic hepatitis and liver cirrhosis were significantly higher than 100, with the SMR of diabetes being as high as 130-140. On the other hand, mortality rate from suicide was significantly lower than that of all of Japan. Regarding malignant neoplasms, morality rates from cancers of all sites, esophagus, stomach, and colon and rectum were significantly lower than 100. However, the SMR of liver cancer was significantly high, suggesting that hepatitis C virus infection was endemic. The reason for the high mortality from diabetes should be clarified with regard to environmental and genetic factors, and the way of reporting diabetes as a cause of death in death certificates. In addition, the reason for the low mortality from cancers of the gastrointestinal tract remains unknown, and further investigations on life style factors are required

トクシマケン ニオケル ヒョウジュンカ シボウヒ : 20 ネンカン ノ ネンジ スイイ オヨビ ホケンジョ カンナイベツ ノ ブンセキ

To elucidate the mortality characteristics of Tokushima Prefecture, the authors analyzed the time-related change in the standardized mortality ratio （SMR） of cause-specific death and organ-specific cancer death during 1983-2002, and administrative area-specific SMR during 1993-1998 and 1999-2002. The gender-and 5-year-age-specific and cause-specific death rates in the entire Japanese population were used as the reference mortality, and the population of sex-and-5-year-agespecific category in the census year （1985, 1990, 1995 and 2000） was used as the population of Tokushima Prefecture. Interval estimation of SMR was performed by the exact method, assuming that the number of deaths followed the Poisson distribution. In the analysis of each year from 1983 to 2002, the SMR of diabetes mellitus markedly increased from the mid 1990’s, suggesting the changes in the environmental factors. The SMR of bronchitis, emphysema and asthma was constantly high during the 20 years. In the administrative area-specific analysis, the SMR of diabetes was high in Tokushima and Naruto for both men and women. With regard to malignant neoplasms, the SMR of esophageal cancer was constantly low, while that of liver cancer was constantly high over the 20 years. The SMR of esophageal cancer was low among men in Tokushima and Anan, and among women in Kamojima, while that of liver cancer was high among men and women in Tokushima and among men in Anan. These characteristics were consistent over the recent 10 years, suggesting the involvement of area-specific factors

Associations of dietary patterns with metabolic syndrome and insulin resistance : a cross-sectional study in a Japanese population

The associations of dietary patterns with metabolic syndrome (MetS) and insulin resistance have not been fully investigated in the Japanese population. A cross-sectional study was performed on 513 subjects without treatment for diabetes who had participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan. Frequencies of consumption of 46 foods and beverages were assessed using a questionnaire. MetS was diagnosed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Logistic and linear regression analyses were used to examine the associations of the dietary patterns with the prevalence of MetS, its components, and the Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR). Using principal component analysis, four dietary patterns were extracted : prudent diet (high intake of vegetables and fruits) ; high fat/Western (high intake of fried foods, fried dishes and meat) ; bread and dairy products ; and seafood patterns. After adjustment for sex, age, and other potential confounders, prudent diet pattern scores were inversely correlated with the prevalence of reduced serum high-density lipoprotein cholesterol (P=0.04) and high blood pressure (P=0.05), and bread and dairy products pattern scores were correlated with a lower prevalence of abdominal obesity (P=0.04) and high plasma glucose (P=0.04). The high fat/Western pattern was positively correlated with HOMA-IR (P=0.04). Prudent dietary pattern and bread and dairy products pattern may be correlated with a lower prevalence of some components of MetS. A high fat/Western dietary pattern may be positively associated with insulin resistance in the Japanese population

セイカツ シュウカン ト コツソショウショウ : キジャクセイ コッセツ ノ ヨボウ

Osteoporosis is a chronic skeletal condition characterized by impaired bone strength and increased risk of fracture. This disorder causes notable morbidity, deterioration in quality of life （QOL）and mortality in the elderly due to associated with fragility fractures of the spine, hip and wrist. Moreover, the treatment of osteoporotic fractures is also associated with a huge economic cost for society. To avoid the fragility fracture, prevention of osteoporosis and fall down are of great importance. For that purpose, not only pharmacological therapy（mainly by antiresorptive medications） in middle-aged and elderly individuals but also non-pharmacological intervention through lifestyle modification will become important in adolescents and young adults from the early life. Lifestyle modification emphasizing bone health such as adequate calcium, vitamin D and vitamin K nutrition, restriction of caffeine and alcohol consumption, and avoidance of tobacco are essential to the management of osteoporosis risk. Balance and strength training also play important roles in the improvement of bone strength. Most of the risk and preventive factors of osteoporosis are common to those of other lifestylerelated diseases. Therefore, lifestyle modification emphasizing bone health from the early life will contribute to avoid not only fragility fracture but also other lifestyle-related diseases, and will contribute to maintenance or improvement of QOL

Quantitative analysis of the effects of nicotinamide phosphoribosyltransferase induction on the rates of NAD+ synthesis and breakdown in mammalian cells using stable isotope-labeling combined with mass spectrometry.

NAD+ is mainly synthesized from nicotinamide (Nam) by the rate-limiting enzyme Nam phosphoribosyltransferase (Nampt) and degraded to Nam by NAD+-degrading enzymes in mammals. Numerous studies report that tissue NAD+ levels decrease during aging and age-related diseases and suggest that NAD+ replenishment promotes healthy aging. Although increased expression of Nampt might be a promising intervention for healthy aging, forced expression of Nampt gene, inducing more than 10-fold increases in the enzyme protein level, has been reported to elevate NAD+ levels only 40-60% in mammalian cells. Mechanisms underlying the limited increases in NAD+ levels remain to be determined. Here we show that Nampt is inhibited in cells and that enhanced expression of Nampt activates NAD+ breakdown. Combined with the measurement of each cell's volume, we determined absolute values (μM/h) of the rates of NAD+ synthesis (RS) and breakdown (RB) using a flux assay with a 2H (D)-labeled Nam, together with the absolute NAD+ concentrations in various mammalian cells including primary cultured cardiomyocytes under the physiological conditions and investigated the relations among total cellular Nampt activity, RS, RB, and the NAD+ concentration. NAD+ concentration was maintained within a narrow range (400-700 μM) in the cells. RS was much smaller than the total Nampt activity, indicating that NAD+ synthesis from Nam in the cells is suppressed. Forced expression of Nampt leading to 6-fold increase in total Nampt activity induced only a 1.6-fold increase in cellular NAD+ concentration. Under the conditions, RS increased by 2-fold, while 2-fold increase in RB was also observed. The small increase in cellular NAD+ concentration is likely due to both inhibited increase in the NAD+ synthesis and the activation of its breakdown. Our findings suggest that cellular NAD+ concentrations do not vary dramatically by the physiological fluctuation of Nampt expression and show the tight link between the NAD+ synthesis and its breakdown