BACKGROUNDIn an earlier study, we identified a locus for Moyamoya disease (MMD) on 17q25.3.

METHODSLinkage analysis and fine mapping were conducted for two new families in additional to the previously studied 15 families. Three genes, CARD14, Raptor, and AATK, were selected based on key words, namely, "inflammation", "apoptosis", "proliferation", and "vascular system", for further sequencing. A segregation analysis of 34 pedigrees was performed, followed by a case-control study in Japanese (90 cases vs. 384 controls), Korean (41 cases vs. 223 controls), Chinese (23 cases and 100 controls), and Caucasian (25 cases and 164 controls) populations.

RESULTSLinkage analysis increased the LOD score from 8.07 to 9.67 on 17q25.3. Fine mapping narrowed the linkage signal to a 2.1-Mb region. Sequencing revealed that only one newly identified polymorphism, ss161110142, which was located at position -1480 from the transcription site of the Raptor gene, was common to all four unrelated sequenced familial affected individuals. ss161110142 was then shown to segregate in the 34 pedigrees studied, resulting in a two-point LOD score of 14.2 (P = 3.89 × 10(-8)). Its penetrance was estimated to be 74.0%. Among the Asian populations tested (Japanese, Korean, and Chinese), the rare allele was much more frequent in cases (26, 33, and 4%, respectively) than in controls (1, 1, and 0%, respectively) and was associated with an increased odds ratio of 52.2 (95% confidence interval 27.2-100.2) (P = 2.5 × 10(-49)). This allele was, however, not detected in the Caucasian samples. Its population attributable risk was estimated to be 49% in the Japanese population, 66% in the Korean population, and 9% in the Chinese population.

CONCLUSIONss161110142 may confer susceptibility to MMD among East Asian populations.

ELECTRONIC SUPPLEMENTARY MATERIALThe online version of this article (doi:10.1007/s12199-009-0116-7) contains supplementary material, which is available to authorized users.

Chronic infection and inflammation contribute to a substantial part of environmental carcinogenesis. Recently, it has been estimated that chronic inflammation accounts for approximately 25% of cancer cases. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species, which are generated from inflammatory and epithelial cells, may play an important role in carcinogenesis by causing DNA damage. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. In an earlier publication, our group reported the results of an immunohistochemical analysis of animals infected with the liver fluke Opisthorchis viverrini and demonstrated for the first time that 8-nitroguanine was formed at the sites of carcinogenesis. This DNA lesion was found to accumulate in the carcinogenic process in clinical specimens of cancer-prone inflammatory diseases caused by various pathogens, including human papillomavirus and Epstein-Barr virus. Moreover, strong 8-nitroguanine formation in tumor tissues was closely associated with a poor prognosis. On the basis of these findings, 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related carcinogenesis and the prognosis of cancer patients. In this review, the significance of 8-nitroguanine formation in inflammation-related carcinogenesis and tumor progression will be discussed.

OBJECTIVESWe have attempted to upgrade and validate an in-house cDNA microarray system developed by our group for the evaluation of chemical toxicity.

METHODSTo establish an in-house microarray, we selected genes that play pivotal roles in detoxifying exogenous substances and maintaining homeostasis in the liver. To validate the system, we examined gene expression profiles in mouse liver following treatment with different doses of carbon tetrachloride (CCl(4)). The data were also analyzed by pathway analysis tools.

RESULTSWe upgraded our array system by collecting genes that are responsive to xenobiotic receptors, apoptosis-related genes, and stress-responsive genes. The acute toxicity of CCl(4) was confirmed by elevated levels of serum transaminase and histopathological findings. The microarray data showed the CCl(4) treatment induced significant changes in gene expression in the mouse liver, and the ingenuity pathways analysis revealed alterations in gene expression in inflammation-related networks.

CONCLUSIONSWe have established a focused microarray system that may be useful for use in toxicogenomics studies. Using this array system, we gained insight into the mechanisms by which CCl(4) exerts its toxic effects. The results of our study also indicate that the combination of focused arrays and bioinformatics tools is helpful in the mechanistic analysis of chemical toxicity.

OBJECTIVESThe present study aimed to define the framework of an environment conducive to the well-being of children with intellectually disability (CID).

METHODSA questionnaire composed of 31 items was developed through literature review. Then a 2-round Delphi survey was conducted with 3 different panels: health professionals (HPs), parents of CID, and teachers. The participants were asked to rate each item, select and rank the 10 most important items, and suggest additional ones.

RESULTSA total of 71 participants responded to the first round: 24 HPs, 22 parents, and 25 teachers. In the second round the overall response rate was 83%. At the end of the exercise, 12 items reached global consensus, i.e., in all groups. Only 5 items were ranked as most important by all groups: attitudes of family members at home; attitudes of HPs and teachers; support from family members at home; support at school (classmates and teachers); and government policies. Nevertheless, the panelists' views diverged on the remaining items. Several additional elements were suggested.

CONCLUSIONSThe views of HPs, teachers, and parents are complementary for the improvement of quality of life (QOL) of CID. The present findings will be used as a basis for the development of an instrument to assess the living environment of CID.

OBJECTIVESWe evaluated the effectiveness and safety of a disinfectant newly developed by our laboratories for use against influenza viruses.

METHODSThe effectiveness of our new disinfectant against avian, swine and human influenza viruses was tested in ovo. The acute toxicity of this disinfectant to two different cultured cell lines was investigated.

RESULTSThis new disinfectant showed very strong anti-influenza viral activity in the in ovo tests. All of the influenza viruses tested were inactivated very quickly. Following exposure to the disinfectant, the infectivity of all viral strains tested had been eliminated within ≤10 min. The infectant showed a weak acute toxicity in vitro.

CONCLUSIONThis new disinfectant is expected to be useful for preventing viral infection during a new influenza pandemic.

OBJECTIVESThe purpose of the study was to investigate the smoking habits of medical and other students and to explore the most important factors associated with students' smoking.

METHODSUniversity students were surveyed in late spring 2006 regarding their smoking status and additional health- and behavior-related characteristics.

RESULTSA total of 1205 (269 medical and 936 nonmedical) students participated in the study. Of these 47% reported being current smokers (35% among medical students), and 30% of the smokers had already started smoking at the age of 16 years. Smokers reported a significantly higher prevalence of cough and respiratory infections and a decrease in physical fitness. The most important factor associated with smoking prevalence was friendship with smokers and maternal smoking. A better knowledge of harmful effects showed a strong association with nonsmokers. Although nonmedical students exhibited a greater possibility to be a smoker, awareness of harmful effects among medical students was not as significant as factor against smoking compared with among nonmedical students.

CONCLUSIONSThis study shows that smoking prevalence among medical and other students in Greece is extremely high. A lack of effective education against smoking in medical students was evident and this underlines the need to identify the factors to be included in planning effective antismoking programs.

OBJECTIVESThis study is aimed at the evaluation of countermeasures in terms of the total number of patients and deaths, the number of vaccine doses used, and the time for eradication as examined through simulations of the outbreak of smallpox following a bioterrorist attack in the center of Okayama City. Three countermeasures were considered: traced vaccination (TV), mass vaccination (MV), and school closure.

METHODSAn individual-based model was adopted, in which every individual is assigned their own personal information, behavioral pattern, and interactions among social settings to simulate the situation on a realistic basis. The influence of residual immunity obtained by past vaccination reflected age-dependent immunity to smallpox in Japan.

RESULTSMV performed within a 2-day period at the same time in 10 school districts had the highest effectiveness in reducing the total number of patients and deaths among all simulations. Performing both TV and MV simultaneously was much more effective than performing TV or MV individually. The decrease in the number of patients with TV or MV in combination with school closure was faster than that by TV or MV without school closure.

CONCLUSIONSAccording to the simulations results, it was advisable to carry out MV, or both TV and MV, simultaneously with school closure as countermeasures against a smallpox epidemic initiated by a bioterrorist attack.

OBJECTIVEThe association between clustering health-promoting components of lifestyle and bone status was examined among middle-aged women.

METHODSA cross-sectional study was conducted in Tadami Town, Fukushima Prefecture, Japan, in 2007. A total of 305 middle-aged women (mean age 55.2 years) participated. The Health-Promoting Lifestyle Profile II was used to assess health-promoting components of lifestyle. Participants' bone status was examined using quantitative ultrasonic calcaneal measurement.

RESULTSA total of 139 participants (45.6%) were defined as having low bone stiffness. In the low bone stiffness group, the mean age was significantly higher, and prevalence of interpersonal relationships score over 3.0 was lower than that in the normal bone stiffness group. There were significant trends in the prevalence of low bone stiffness, each health-promoting component of lifestyle, and presence of hypertension and diabetes mellitus, based on the number of frequently selected health-promoting components of lifestyle. The number of frequently selected health-promoting components of lifestyle correlated negatively with the prevalence of low bone stiffness in both crude and adjusted results.

CONCLUSIONThis research is particularly important as we suggest health-promotion strategies for the prevention of osteoporosis. A synthetic approach, which includes health responsibility, spiritual growth, interpersonal relations, and stress management, and physical activity and nutrition, may be effective and complement traditional strategies.

OBJECTIVESA lower vital capacity (VC) has been reported to be an independent predictor of diabetes in Western countries. The aim of this study was to examine the relationships between VC and diabetes and between VC and metabolic syndrome (MS) in Japanese individuals.

METHODSStepwise multiple linear regressions with fasting glucose as a dependent variable and age, metabolic risk factors, and percentage vital capacity (%VC) as independent variables were performed using data obtained from 1651 men and 957 women. Area under the receiver operating characteristic curve (AUC) of -%VC for diagnosing diabetes, MS, and Japanese MS (JMS) were calculated, and stepwise logistic regressions using diabetes, MS, and JMS as dependent variables were performed.

RESULTSPercentage vital capacity was independently associated with fasting glucose in men, but not in women. The AUC of -%VC for diagnosing diabetes, MS, and JMS were 0.647, 0.606, and 0.598, respectively (all p < 0.0001) in men and 0.639 (p = 0.065), 0.513 (p = 0.732), and 0.668 (p = 0.01), respectively, in women. Age, waist circumference (WC), and %VC in men and WC and %VC in women were independently associated with diabetes. Age and %VC in men and only age in women were independently associated with MS, and age and %VC in both men and women were independently associated with JMS.

CONCLUSIONSAmong a representative Japanese population, a lower VC was significantly associated with diabetes and MS in men, but the relationships were not conclusive in women.