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Mild hyperhomocysteinemia is one of the known strong risk factors for atherosclerotic diseases, and therefore it is important to clarify factors that could determine plasma total homocysteine(tHcy)level.A cross-sectional study with a random sample of 455 Japanese rural residents aged 40-69 years was conducted in 2000 to investigate the associations of plasma tHcy concentration with 5, 10-methylenetetrahydrofolate reductase(MTHFR)gene and selected life-style related factors.The frequency of the mutant allele, Valine(V)allele, was 0.40 and the prevalence of W genotype was 14.3 %.Plasma tHcy concentration in W was significantly higher than those in two other genotypes.There were significant inverse associations of plasma tHcy with serum folate and serum vitamin B12(P

1542 Background: Squamous cell dysplasia and carcinoma in the upper aerodigestive tract (UAT) was frequently accompanied by melanosis in the UAT. Soft palatal melanosis can be detected by visual inspection during routine physical examination or even personally in a mirror. Methods: We reviewed digitalized records of high-quality endoscopic images of the soft palate of 1786 Japanese alcoholic men who underwent endoscopic screening combined with esophageal iodine staining and evaluated to what extent the presence of soft palatal melanosis combined with other risk factors can predict the risk of UAT neoplasia. Results: Soft palatal melanosis was observed in 381 (21·3%) of the subjects (mild, 15·0%; distinct, 6·3%). An older age, an inactive heterozygous aldehyde dehydrogenase-2 genotype, smoking, and a high mean corpuscular volume (MCV) were positively associated with the presence of soft palatal melanosis. The age-adjusted odds ratio (OR [95% CI]) for neoplasia in the UAT was 1·92 [1·40–2·64] in the group with melanosis and 2·51 (1·55–4·06) in the group with distinct melanosis, compared with the melanosis-free group. A multiple logistic analysis including the alcohol and aldehyde dehydrogenases genotypes and non-genetic risk factors showed that the presence of soft palatal melanosis was independently associated with a high risk of neoplasia in the UAT. We calculated the individual number of risk factors out of four easily identifiable and significant factors: age ≥55 years, current/former alcohol flushing, MCV ≥106 fl, and distinct soft palatal melanosis. Compared with the risk-factor-free condition, the OR (95% CI) values of UAT neoplasia for one, two, three and four risk factors were 1·49 (0·97–2·30), 3·14 (2·02–4·88), 4·80 (2·71–8·51) and 7·80 (2·17–28·1), respectively. Conclusions: Soft palatal melanosis combined with other simple risk assessments provides a simple new strategy for identifying heavy drinkers with a high risk for UAT neoplasia.

Background Alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians. We invented a health risk appraisal (HRA) model for predicting the risk of ESCC based on drinking, smoking, dietary habits, and alcohol flushing, i.e., past or present facial flushing after drinking a glass of beer, a surrogate marker for inactive ALDH2. Methods Prospective follow-up examinations (median follow-up time, 50.3 months) were performed in 278 Japanese men after endoscopic mucosectomy for early ESCC (UMIN Clinical Trials Registry ID: UMIN000001676). Results Sixty-four subjects developed metachronous ESCC. A receiver operating characteristic curve showed that HRA scores ≥12 best predicted the development of metachronous ESCC. The ESCC detection rate per 100 person-years was 9.8 in the high-HRA-score group (n = 104) and 4.5 in the low-HRA-score group (n = 174), and the risk of development of metachronous ESCC was higher in the high-HRA-score group than in the low-HRA-score group (adjusted hazard ratio: 2.00 [95% CI: 1.12-3.30]). Multiple LVLs was a very strong predictor of the development of metachronous SCC, but high HRA scores predicted it independently. The cumulative incidences of metachronous ESCC decreased after drinking cessation in the high-HRA-score drinker group (adjusted hazard ratio: 0.37 [0.14-0.97]). Conclusions Both the HRA model that included alcohol flushing and the multiple LVL grade predicted the development of metachronous ESCC in Japanese men after endoscopic mucosectomy for ESCC. Drinking cessation in the high-HRA-score drinker group reduced the rate of metachronous ESCC.

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV≥106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1 %) and head and neck SCC (1.0 %). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈ 180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0 % of 4,879 alcoholics had a history of (4.0 %) or newly diagnosed (1.0 %) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7 % of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5 % of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV ≥ 106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.

Background In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. Methods In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. Results Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group. Conclusions A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.

Background: Waist circumference (WC) is used as a risk assessment for metabolic syndrome, diabetes, and cardiovascular disease (CVD). WC consists of visceral fat area (VFA), subcutaneous fat area (SFA), muscle, intramuscular fat, viscera, and bone. Each component of the WC may differ between the sexes and generations, even if they have the same WC. However, this has not been measured in an epidemiological study. Methods: Between 2004 to 2009, employees and their spouses working at a Japanese company underwent a health examination after more than 12 hours of fasting. We analyzed the data of 11,570 subjects (9,874 men and 1,696 women), aged from 20 to 76 years, who underwent a computed tomography (CT) examination. VFA, SFA, WC, muscle, intramuscular fat, viscera, and bone were measured using a CT scanner. We conducted stratified analyses by generational age, and calculated the Pearson’s correlation coefficients between the VFA and WC, BMI, and VFA plus SFA. To establish the equations for converting the WC to the corresponding VFA and VFA plus SFA, linear regression analyses were used to obtain the regression coefficients and intercepts. Results: As the generations increased in age, the VFA tended to increase. However, the differences in the WC values of each generation did not coincide with the VFA values in men (r = �0.275 and 0.979 for men and women, n = 5 generations), but did correlate with the difference in the sum of the VFA plus SFA for both sexes (r = 0.915 and 0.996 for men and women, n = 5 generations). Older generations had lower WC values when they had the same VFA values as the younger generations. Conclusions: The WC value corresponding to a certain VFA value differed significantly by generational age. Thus, revised optimal cutoff values for the WC may be needed for each generation.

BACKGROUND: Recent reports on Propionibacterium acnes (P. acnes) suggest that this bacterium is prevalent in the prostate, is associated with acute and chronic prostatic inflammation, and might have a role in prostate carcinogenesis. METHODS: To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in radical prostatectomy specimens using enzyme immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL antibody), together with an anti-nuclear factor-kappa B (NF-κB) antibody. We examined formalin-fixed and paraffin-embedded tissue sections of radical prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched control patients with bladder cancer, but without prostate cancer. RESULTS: Immunohistochemistry with the PAL antibody revealed small round bodies within some non-cancerous glandular epithelium and stromal macrophages in most prostate samples. Prostate cancer samples had higher frequencies of either cytoplasmic P. acnes or nuclear NF-κB expression of glandular epithelium and higher numbers of stromal macrophages with P. acnes than control samples. These parameters were also higher in the peripheral zone than in the transitional zone of the prostate, especially in prostate cancer samples. Nuclear NF-κB expression was more frequent in glands with P. acnes than in glands without P. acnes. The number of stromal macrophages with the bacterium correlated with the grade of chronic inflammation in both the PZ and TZ areas and with the grade of acute inflammation in the TZ area. CONCLUSIONS: Immunohistochemical analysis with a novel monoclonal antibody for detecting P. acnes in the prostate suggested that intraepithelial P. acnes infection in non-cancerous prostate glands and inflammation caused by the bacterium may contribute to the development of prostate cancer.

The role of vitamin C as an antioxidant in reducing oxidative stress is widely known. Epidemiologic studies have associated greater plasma vitamin C levels with reduced risk of chronic diseases, including cancer and cardiovascular disease, as well as higher physical performance in the elderly. However, there is little understanding regarding the mechanisms that explain the effects that vitamin C may have on physical performance and aging, and the literature presents inconsistent and contradictory results. While vitamin C may reduce the muscle damage caused by oxidative stress and reactive oxygen species, recent study has begun to branch into exploration of its effects on markers of mitochondrial biogenesis. There is evidence from intervention studies which suggest that vitamin C may hamper performance, yet opposing results, revealing that vitamin C does not hinder performance, have also been presented. Regardless, vitamin C in adequate amounts is necessary for muscle function, and diets high in fruits and vegetables are recommended.

Purpose: To evaluate the functional status in daily life and the quality of life (QOL) of pathologic myopia patients. Methods: A cross-sectional study was conducted using data of consecutive pathologic myopia patients (n = 200) and control subjects (n = 144). The influence of the disease on the daily life and the QOL of patients were evaluated using a self-rated questionnaire. The questionnaire covered the full range of daily life activity, including daily tasks depending on visual acuity, social and emotional handicaps, and cognition of disease, and the QOL of pathologic myopia patients. Results: The functional status in daily life and the QOL of patients were reduced compared with control subjects. The influence of pathologic myopia on a patient's daily life was primarily the result of three major factors, handicap, disability, and support. All three factors correlated with the QOL, the degree of handicap having the strongest correlation. Conclusion: The functional status in daily life and the QOL of pathologic myopia patients were reduced; this decline in QOL was attributed to handicap and disability caused by the ocular disease.

OBJECTIVE We examined the relationships of visceral fat area (VFA), subcutaneous fat area, and waist circumference, determined using computed tomography (CT), and BMI with metabolic risk factors in a large Japanese population. RESEARCH DESIGN AND METHODS Study subjects comprised 6,292 men and women who participated in the Hitachi Health Study and received CT examinations in 2007 and 2008. RESULTS Regarding the clustering of metabolic risk factors, the odds ratios (ORs) for the VFA quintiles were 1.0 (ref.), 2.4, 3.4, 5.0, and 9.7 for men and 1.0 (ref.), 1.5, 2.6, 4.6, and 10.0 for women (P < 0.001 for trends in both sexes). For the highest quintiles, the OR for VFA was 1.5 to 2 times higher than those of the other anthropometric indexes in both sexes. CONCLUSIONS We demonstrated a superior performance of VFA to predict the clustering of metabolic risk factors compared with other anthropometric indexes.

We examined the correlation between the prefectural variation of standardized mortality ratio (SMR) for lung and colon cancer and the consumption of foods using dietary data from National Nutrition Survey in Japan from 1976 to 1995. We found partly the same results on promoting factors and preventing factors of these cancers as the previously reported large scale cohort studies. But, we also found the inconsistent results. This might be partly because of the limitation of data collection method in the National Nutrition Survey. It was thought that the method of National Nutrition Survey should be modified to monitor nutrition and health conditions to correspond the epidemiological study and to prevent chronic diseases.

Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2 * 2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 * 2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers.

The reliability and validity of two newly developed densitometric methods for determining the human body volume and percent body fat (%FAT), the sulfur hexafluoride dilution method (SHF) and air displacement plethysmography (ADP), were evaluated in comparison with the underwater weighing method (UWW). Seven healthy male volunteers (age 31 to 44, mean height 166.0 cm, weight 61.4 kg) participated in this study. The same-day test-retest coefficients of variation (CVs) for body volume and %FAT measurements were not significantly different among the three methods. SHF and UWW showed a strong correlation in terms of body volume and %FAT, with the correlation coefficients (r) being 0.9997 and 0.986, respectively. The correlation between ADP and UWW was slightly weaker (r = 0.9997 for body volume and 0.907 for %FAT). However, body volumes measured by SHF and ADP were significantly different from that by UWW when compared by mean values. Such differences were also found for %FAT measurements. The regression lines of body volume measured by SHF and ADP on that by UWW were almost equivalent to the line of identity. However, those of %FAT measured by SHF and ADP on that by UWW were significantly different from the line of identity. Because the reliability of SHF and ADP appeared to be high, further validation and improvement are required and worth doing.

Abstract The association between apolipoprotein (apo) genetic polymorphisms and lipid phenotypes remains to be determined because such studies have reported contradictory results. We have measured plasma total cholesterol (TC) and HDL cholesterol (HDL-C) in a cross-sectional sample of 1328 (462 men and 866 women) Japanese (aged 40 to 80 years) and analyzed their DNA for the following genotypes: apoA1-C3 Msp I and Sst I sites; apoB signal peptide insertion/deletion, Xba I site and 3′ variable number of tandem repeats (VNTR); and apoE. Using multivariate analyses (ANOVA) we found that (1) the polymorphisms of apoA1-C3 and apoB genes are not significantly associated with TC or HDL-C and (2) the polymorphism of the apoE gene is significantly related with TC and the TC:HDL-C ratio. The ε2 carriers have lower levels of TC and a lower TC:HDL-C ratio, ε3 carriers have intermediate levels, and ε4 carriers have higher levels. These findings held whether sexes were analyzed separately or together. Although an opposite trend in HDL-C levels was observed, it did not reach the level of statistical significance. Multiple regression analyses have shown that apoE polymorphism accounts for about 2.3% of the variation in TC and TC:HDL-C ratio irrespective of sex. When the subjects are divided into two groups according to their age (≤59 and ≥60 years old), the effect of apoE alleles on serum cholesterols appears to be diluted in the younger age group whereas it appears to be accentuated in the older group for both sexes. Our findings suggest that among the apo genetic polymorphisms examined, the apoE gene may be considered as a possible candidate for the “high-risk” strategy of atherosclerosis prevention in the Japanese population.

To investigate the relation between observer performance for blood pressure measurement in a training process and in field conditions, measurement values were studied under training and field conditions among 21 blood pressure observers of 1434 subjects aged 6-15 years in Japan. The observers received training by a videotape, which included six audiovisual presentations of a falling mercury column in a standard sphygmomanometer with Korotkoff sounds. Observer bias was measured for each trainee as the mean difference between the observed and the standard values for each blood pressure reading, including systolic (SBP), fourth-phase diastolic (K4), and fifth-phase diastolic (K5) values. In multiple linear regression analyses, each 1 mmHg increment in observer bias was equivalent to 1.27, 0.88, and 1.25 mmHg difference in actual readings of SBP, K4, and K5, respectively, in the field. This finding indicates that observer performance in videotape training is predictive of measurement behavior in the field.

BACKGROUND Variation of plasma total homocysteine (tHcy) levels among individuals is modified by 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and selected atherosclerotic risk factors. DESIGN Cross-sectional study. METHODS Healthy Japanese men (n=213) and women (n=242) aged 40-69 years were examined. RESULTS Serum uric acid, hemoglobin, hematocrit, serum creatinine, and men were independently significantly associated with plasma tHcy. The relationship between serum uric acid and plasma tHcy was the strongest in those with the mutant homozygote (VV), but the overall statistical test of interaction was not significant. CONCLUSIONS Serum uric acid, hematocrit, hemoglobin, creatinine, and men were determinants of plasma tHcy levels. Further investigations are needed.

Midwives are actively involved in providing dietary advice to pregnant women. In order to describe the current status of prenatal dietary advice provided by midwives, we conducted a questionnaire survey inquiring about their knowledge and usage of the "Dietary Guidelines for Pregnant and Lactating Women" (Guidelines) issued by the Ministry of Health, Labour, and Welfare in 2006.In total, 2000 members of the Japanese Midwives' Association were randomly selected for administration of the questionnaire. The recovery rate was 42.1%, and 785 responses were eligible for analyses. The questionnaire collected information on the respondent's age, years of work experience, current involvement in delivery practice, number of deliveries per year in the current affiliation, provision of dietary advice to pregnant women, and knowledge and usage of the Guidelines.The proportion of respondents in their 20 s was low (1.8%). About half of the respondents were practicing delivery. Further, 66.1% (519 midwives) reported they had knowledge of the Guidelines. Among those who had knowledge of the Guidelines and were currently providing dietary advice (426 midwives), 88.0% were using the Guidelines. The most frequently used item in the Guidelines was "Diet for preventing anemia" (75.8%). The least used item was "Shoku-iku (diet and nutrition education) for pregnant and lactating women" (58.5%). Midwives who were practicing delivery showed a significantly lower usage of the Guidelines than those who were not (84.9% vs. 92.6%, P = 0.02). Among midwives practicing delivery, the most common reason for not using the Guidelines was "using original educational material produced by oneself or the facility."Providing dietary advice to pregnant women constituted a large fraction of midwives' duties as well as delivery practice. About 90% of the midwives, who had knowledge of the Guidelines and provided dietary advice, were using the Guidelines. In order to increase the usage of individual items of the Guidelines, ready-to-use brochures should be developed for midwives.

The distribution of usual intake of nutrients in a given population is one of the major concerns in public health nutrition, and is used to assess and prevent nutritional problems. The distribution of usual intake cannot be measured directly, but can be estimated from a dietary survey that spans multiple days. The prevalence of nutritionally high-risk people, defined as the proportion of a population that does not achieve the dietary reference intake, can be estimated from the distribution of usual intake in the population. Although several methods have been proposed, there is no universally accepted method for estimating the distribution and prevalence of nutritionally high-risk people. In this study, we improved an existing method and used simulation studies to compare the performance of the new method, with that of 2 previously proposed methods. Our proposed method outperformed them, particularly in a realistic situation, and with a small sample size, providing a more accurate and precise estimate of the prevalence of nutritionally high-risk people.

In this study, 1,000 Japanese male alcoholics were consecutively screened by upper gastrointestinal endoscopy with esophageal iodine staining. Associations among cancer-detection rates, drinking and smoking habits, and aldehyde dehydrogenase-2 (ALDH2) genotypes were evaluated. A total of 53 patients (5.3%) had histologically confirmed cancer. Esophageal cancer was diagnosed in 36, gastric cancer in 17, and oropharyngolaryngeal cancer in 9 patients: 8 of the esophageal-cancer patients were multiple-cancer patients, with additional cancer(s) in the stomach and/or oropharyngolaryngeal region. Multiple logistic regression revealed that use of stronger alcoholic beverages (whisky or shochu) in contrast with lighter beverages (sake or beer) and smoking of 50 pack-years or more increased the risks for esophageal (odds ratio 3.2 and 2.8 respectively), oropharyngolaryngeal (4.8 and 5.1 respectively) and multiple cancer (10.5 and 11.8 respectively). The inactive form of ALDH2, encoded by the gene ALDH2*1/2*2 prevalent in Orientals, exposes them to higher blood levels of acetaldehyde, a recognized animal carcinogen, after drinking. This inactive ALDH2 was detected in 19/36 (52.8%) patients with esophageal cancer, in 5/9 (55.6%) patients with oropharyngolaryngeal cancer, and in 7/8 (87.5%) patients with multiple cancer. All of these gene frequencies far exceeded that in a large alcoholic cohort (80/655, 12.2%). The triple combination of the risk factors of the inactive ALDH2, stronger alcoholic beverages and heavy smoking was more commonly associated with multiple-cancer patients than with patients with esophageal cancer alone (62.5% vs. 7.1%). These results show that the 3 risk factors are important for the development of upper-aerodigestive-tract cancer in Japanese alcoholics. For these high-risk drinkers, regimented screening appears to be indicated. © 1996 Wiley-Liss, Inc.

The aim of this report is to describe age-adjusted death rates from ischemic heart diseases (IHD) and cerebrovascular diseases (CVD) in recent years and secular trends in the selected countries. World Health Statistics Annuals by the World Health Organization were used for data sources. From 1994 annual statistics, among males, the countries with the highest age-adjusted death rates were as follows in decreasing order: Hungary, former Czechoslovakia, the United Kingdom, Ireland and Finland for IHD; Bulgaria, Hungary, Portugal, former Czechoslovakia and Poland for CVD. On the other hand, the countries with the lowest rates were as follows in increasing order: Japan, France, Spain, Portugal and Italy for IHD; Switzerland, Canada, the United States, France and Australia for CVD. The trends of age-adjusted death rates both in IHD and CVD for 1970-1994 decreased in the United States, Australia, Western and Southern Europe and Japan, while both IHD and CVD rates tended to increase in Eastern Europe. Decreasing trends seen in the countries that already showed marked decrease in 1970s through the mid 1980s, seemed to be blunted in recent years. Some countries whose death rates were relatively high showed decreasing trends that lagged behind the other countries: Spain, Poland and Greece for IHD; and Hungary for CVD. J Epidemiol, 1996 ; 6 : S189-S196.

A 15.5-year follow-up study of ischemic heart disease among residents 40 years and older in a rural community, A-I district, Shibata City, Niigata Prefecture, Japan, was completed in 1992. The response rate for the initial examination was 84.5% of 1, 182 men and 92.6% of 1, 469 women. Nine hundred and eighty-five men and 1, 344 women who were initially free of ischemic heart disease were followed from July 1977 through December 1992. The person-year incidence of possible myocardial infarction (PMI) was 1.01 per 1, 000 for men and 0.59 for women, and that of sudden death within 24 hours (24SD) was 1.08 for men and 0.64 for women. In the sex-, and age-stratified univariate analyses by the Cox proportional hazard regression model, statistically significant relative risk of PMI was observed for systolic (SBP), diastolic (DBP) and mean blood pressure (MBP), body mass index and smoking. For 24SD, DBP and albuminuria were selected as significant risk factors. In the multivariate analyses, MBP and smoking were selected as independent risk factors for PMI. No significant association of any factor with 24SD was detected. The influence of serum cholesterol on occurrence of PMI appeared to be subtle. J Epidemiol, 1996 ; 6 : 15-22.

The age-adjusted death rate from ischemic heart disease in Japan is the lowest among developed countries and the rates have decreased since 1970. The incidences of myocardial infarction in selected populations ranged between 0.12 and 2.56 per 1, 000 for middle-aged males, and between 0.00 and 1.52 per 1, 000 for females. The incidences of sudden death within 24 hours were from 0.00 to 1.58 per 1, 000 for males and from 0.00 to 0.76 per/1, 000 for females. The incidences in Japanese populations appeared to be far below those in Western populations. In the Cox proportional hazard regression model, hypertension and smoking were selected as independent risk factors for myocardial infarction in an agricultural district. It was noteworthy that the level of serum cholesterol was not associated with development of myocardial infarction in rural areas. No positive relation between dietary fat and serum cholesterol was observed in school children, suggesting that growth, sexual maturation and others might be confounding variables between them. The levels of serum cholesterol for females were more affected by menopause than those of blood pressures and body mass index. Although some polymorphisms in selected candidate genes appeared to be associated with some serum lipids and apolipoproteins, the effect of individual RFLP on the inter-individual variations in serum traits was relatively subtle in comparison with that of lifestyle factors. J Epidemiol, 1996 ; 6 : S49-S59.

This is the first study that we are aware of that followed the his-topathological progression of the liver disease that was caused by the combination of both chronic alcohol use and cyanamide, an an-tidipsotropic agent. Two sequential liver biopsy specimens were obtained on 29 alcoholics who relapsed with varying histories of cyan-amide treatment. Cyanamide induced ground-glass inclusions (GGIs) in the hepatocytes. Two groups were identified, depending on whether GGIs proliferated or regressed, which was, in turn, found contingent on the duration of cyanamide treatment and the drug-free period. Group 1 included 14 cases in which GGIs either emerged only in the second biopsy specimen or else were increased in the second specimen as compared in the initial specimen. Group 2 composed of 15 cases in which GGIs were either not observed in either specimen or decreased in the second specimen as compared in the initial specimen. Acidophilic bodies were sequentially increased in five cases (36%) of group 1 and in none of group 2. The severity of portal inflammation worsened in 10 cases (71%) of group 1 but in 2 cases (13%) of group 2, although the changes in fibrotic process did not differ between two groups. These differences could not be explained on the basis of the daily ethanol consumption and the length of relapses of the two groups. Thus, when cyanamide-treated alcoholics relapsed, the combined effect of cyanamide and alcohol produced the development of acidophilic bodies and portal inflammation along with the emergence of GGIs.

The rare allele frequency of the restriction fragment length polymorphism (RFLP) with Xba I (X+) at the apolipoprotein B (apo B) gene locus was 0.041 in men and 0.026 in women in H-Y district, Shiso County, Hyogo Prefecture, Japan : EcoR I at apo B gene (E-)=0.073 and 0.076, Msp I at apo Al-CIII gene (M-)=0.423 and 0.430, and Sac I at apo Al-CIII gene (S+)= 0.309 and 0.349. There was no marked ageor sex-difference in the frequencies. The frequencies of X+ and Ewere lower and those of S+ and Mwere higher in H-Y district than in Caucasian populations. In this population, according to the ANOVAs, the genotype for EcoR I was significantly (p

Background: The safety of influenza A (H1N1) 2009 among chronic obstructive pulmonary disease (COPD) patients has not been investigated yet. Our objective was to investigate the safety of the A (H1N1) 2009 vaccine, especially for mortality after vaccination. Methods: From October 2009 to March 2010, we collected records from all Japanese hospitals registered in the Japanese Respiratory Society. We conducted a 1:1 matched case-control study. Patients with COPD who died in the study period were determined as case group patients (n=36). Patients with COPD who survived the study period were determined as control group patients (n=36). In the control group selection process, we selected age, sex, period of home oxygen therapy (measure for COPD severity), hospital, and calendar time as matching factors. We then compared the proportion of patients who received the influenza A (H1N1) 2009 vaccine in each group and evaluated the conditional odds ratio. Results: Both the case and control groups had 36 COPD patients, 32 of whom were men. The mean age was 76.6 years (SD=8.6) in the case group and 76.9 years (SD=8.3) in the control group. The mean period of home oxygen therapy in both groups was 1.8. The proportion of patients receiving A (H1N1) 2009 vaccinations was 47.2% in the case group and 63.9% in the control group. The crude conditional odds ratio of mortality in the winter was 0.33 (95% confidence interval: 0.06-1.34) and adjusted conditional odds ratio was 0.37 (95% confidence interval: 0.09-1.52) with no significance. Conclusions: Our study detected no statistically increased risk of mortality after influenza A (H1N1) 2009 vaccination among COPD patients. The results are, however, limited by the small sample size and low statistical power. A similar larger-scale study is needed in the future to confirm our findings., Journal of Vaccines & Vaccination, 3(5); 2012

Higher-level competence is crucial for healthy and socially independent living, and general intelligence may underlie heath status. The aim of this study was to elucidate associations between general intelligence and higher-level competence in elderly individuals without dementia.A total of 207 community-dwelling elderly persons, aged 70-74 years, were enrolled. A personal interview was performed to obtain data on socio-demographic and medical factors; higher-level competence was evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG index). Raven's Coloured Progressive Matrices (RCPM) test was used to assess general intelligence. Correlations between the TMIG index, its subscale scores and the RCPM score were evaluated by Spearman's rank correlation coefficients. Ordinal regression models were conducted with the TMIG index and its subscales as the dependent variables, RCPM as the principal independent variable, and age, sex, type of household, employment status, educational background, chronic medical conditions and number of natural teeth as the potential independent variables.There were significant but weak positive correlations between total score on the TMIG index, scores on the intellectual activity and social role subscales and RCPM score. In ordinal regression models, RCPM and educational background were significantly associated with total score on the TMIG index and the intellectual activity subscale, and only RCPM was associated with the social role subscale score, after adjusting for other potential variables.General intelligence may be significantly associated with higher-level competence, especially with intellectual activity and social role subscales, in community-dwelling older adults.

To examine the incidences of metabolic risk factors according to changes in visceral fat area (VFA) in a large Japanese population.The subjects were 973 men who received a computed tomography (CT) examination in health checkups twice (2004-2005 and 2007-2008), and not having two or more of metabolic risk factors (except for the waist circumference) in 2004-2005. VFA was measured using CT. To assess the potential influence of changes in VFA for the 3-year incidences of each metabolic risk factor and clustering metabolic risk factors, logistic regression analyses were used.A significant association was observed between the change in VFA and the components of the metabolic risk factors. Incidences of the components of the metabolic risk factors were significantly higher among subjects with a larger increase in VFA and were significantly lower among subjects with a larger decrease in VFA (trend P0.001). Significant increases in the odds ratios for the incidences of high triglycerides and low high-density lipoprotein cholesterol level were observed among subjects with ≥50 cm(2) VFA increase.The adoption of a lifestyle that does not increase the VFA is important for preventing metabolic syndrome.

OBJECTIVE The effects of longitudinal changes in the visceral fat area (VFA), and other anthropometric indices, on the risk factors of metabolic syndrome were not studied. We calculated the changes in metabolic risk factors in relation to changes in certain anthropometric indices in a large-scale study of Japanese men. RESEARCH DESIGN AND METHODS The subjects were 1,106 men participating in the Hitachi Health Study who received a computed tomography examination in both 2004 and 2007. VFA, subcutaneous fat area (SFA), and waist circumference were measured using the computed tomography. We examined how longitudinal changes in each anthropometric index over a 3-year period influenced the value of each metabolic risk factor. RESULTS Changes (∆) over a 3-year period in body weight, SFA, and waist circumference strongly correlated, while the changes in body weight and VFA were weakly correlated. Changes in the VFA were associated with changes in metabolic risk factors, especially changes in triglyceride and HDL; we found these changes to be independent of the ∆body weight and ∆waist circumference. CONCLUSIONS Change in body weight is not a precise surrogate marker of ∆VFA, and repeated VFA measurements over time are useful. Adopting a lifestyle that does not increase the VFA is important in preventing metabolic syndrome.

Background. Maintenance of physical performance could improve the quality of life in old age. Recent studies suggested a beneficial relationship between antioxidant vitamin (eg, vitamin C) intake and physical performance in elderly people. The purpose of this study was to examine the relationship between plasma vitamin C concentration and physical performance among Japanese community-dwelling elderly women. Methods. This is a cross-sectional study involving elderly females residing in an urban area in Tokyo, Japan, in October 2006. We examined anthropometric measurements, physical performance, lifestyles, and plasma vitamin C concentration of participants. Results. A total of 655 subjects who did not take supplements were analyzed. The mean age (±standard deviation) of participants was 75.7 ± 4.1 years in this study. The geometric mean (geometric standard deviation) of plasma vitamin C concentration was 8.9 (1.5) mg/mL. The plasma vitamin C concentration was positively correlated with handgrip strength, length of time standing on one leg with eyes open and walking speed, and inversely correlated with body mass index. After adjusting for the confounding factors, the quartile plasma vitamin C level was significantly correlated with the subject’s handgrip strength (p for trend = .0004) and ability to stand on one leg with eyes open (p for trend = .049). Conclusions. In community-dwelling elderly women, the concentration of plasma vitamin C related well to their

Background The biomarkers of excessive alcohol intake reported thus far have not always been reliable. We discovered the presence of free glycerol (FG) by high-performance liquid chromatography (HPLC) in the serum of alcoholic patients but not in healthy persons, and a higher percentage of the alcoholics were positive for serum FG than for gamma-glutamyl transpeptidase, mean corpuscular volume, or carbohydrate-deficient transferrin (%CDT). Therefore, in this study, we investigated whether the same results as with HPLC could be obtained by measuring FG with an easy-to-use autoanalyzer and whether the serum FG measured by this method would be useful as a biomarker of excessive alcohol intake. Methods First, the measurements of serum FG made by HPLC and by a biochemical method with an autoanalyzer were tested for a correlation, and then fasting serum FG was measured with the autoanalyzer in 3 groups: a group of Japanese male alcoholics who drank until just before admission, a group of Japanese male patients with chronic viral hepatitis, and a group of Japanese healthy male volunteers. Results There was a strong positive correlation between the serum FG values measured by HPLC and by the autoanalyzer in the alcoholic group. The values in the alcoholic group were significantly higher than in the viral hepatitis group and healthy control group. We set the cutoff serum FG value for discriminating between the alcoholic group and the other 2 groups in the receiver operating characteristic analysis at 0.9 mg/dl, and that cutoff value provided a sensitivity of 80% for identifying the alcoholic group and a specificity of 84 and 94% in relation to the viral hepatitis group and the healthy volunteer group, respectively. Among various clinical tests in the alcoholic group, serum FG showed the highest rate of abnormally high value. Conclusions Measurement of serum FG with an autoanalyzer may be useful as a biomarker of excessive alcohol intake.

Low-dose aspirin (LDA) is widely used because it reduces the risk of vascular events in patients with atherosclerosis. Recently, there has been a substantial increase in prescriptions for LDA. We analyzed the risk of colonic mucosal lesions associated with the long-term use of LDA.Among Japanese patients who underwent a colonoscopy between January 2004 and December 2006, 199 colitis cases and 5764 non-colitis controls were identified after excluding 749 patients based on study criteria. The history of LDA use was compared between the cases and controls and the multivariate (age-, sex- and underlying diseases-) adjusted odds ratio (OR) was estimated using a multiple logistic regression model.The adjusted OR for colonic mucosal lesions associated with LDA use versus non-use was 1.45 [95% confidence interval (CI), 0.87-2.42; p = 0.152]. In terms of gender differences, the OR for LDA-induced colitis in females was significantly increased at 2.55 (95% CI, 1.31-4.94; p = 0.006) but was not significantly increased in males at 0.70 (95% CI, 0.34-1.45; p = 0.334).In females, LDA increased the risk of colonic mucosal lesions, suggesting that LDA may contribute to the pathogenesis of colonic ulceration or colitis. Therefore, it is essential that prescribing physicians be aware of the risk of LDA-induced colonic lesions.

Inactive heterozygous aldehyde dehydrogenase-2 ( ALDH2 * 1/ * 2 ) and less-active alcohol dehydrogenase-1B ( ADH1B * 1/ * 1 ) increase the risk of esophageal cancer in East Asian drinkers, and esophageal cancer multiplicity is strongly associated with ALDH2 * 1/ * 2 . p53 alterations are key molecular events in multifocal carcinogenesis in the esophagus. We studied 260 esophageal-cancer free Japanese alcoholics with esophageal dysplasia diagnosed by biopsy of distinct iodine-unstained lesions (DIULs) ⩾5 mm. The degree of p53 protein accumulation was positively associated with the degree of atypia ( p p = 0.040) of DIULs and with the presence of multiple DIULs (p = 0.070), but not with ALDH2 * 1/ * 2 or ADH1B * 1/ * 1 .

The ethanol in alcoholic beverages and the acetaldehyde associated with alcohol consumption are Group 1 human carcinogens (WHO, International Agency for Research on Cancer). The combination of alcohol consumption, tobacco smoking, the inactive heterozygous aldehyde dehydrogenase-2 genotype (ALDH2*1/*2) and the less-active homozygous alcohol dehydrogenase-1B genotype (ADH1B*1/*1) increases the risk of squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) in a multiplicative fashion in East Asians. In addition to being exposed to locally high levels of ethanol, the UADT is exposed to a very high concentration of acetaldehyde from a variety of sources, including that as an ingredient of alcoholic beverages per se and that found in tobacco smoke; acetaldehyde is also produced by salivary microorganisms and mucosal enzymes and is present as blood acetaldehyde. The inefficient degradation of acetaldehyde by weakly expressed ALDH2 in the UADT may be cri! tical to the local accumulation of acetaldehyde, especially in ALDH2*1/*2 carriers. ADH1B*1/*1 carriers tend to experience less intense alcohol flushing and are highly susceptible to heavy drinking and alcoholism. Heavy drinking by persons with the less-active ADH1B*1/*1 leads to longer exposure of the UADT to salivary ethanol and acetaldehyde. The ALDH2*1/*2 genotype is a very strong predictor of synchronous and metachronous multiple SCCs in the UADT. High red cell mean corpuscular volume (MCV), esophageal dysplasia, and melanosis in the UADT, all of which are frequently found in ALDH2*1/*2 drinkers, are useful for identifying high-risk individuals. We invented a simple flushing questionnaire that enables prediction of the ALDH2 phenotype. New health appraisal models that include ALDH2 genotype, the simple flushing questionnaire, or MCV are powerful tools for devising a new strategy for prevention and screening for UADT cancer in East Asians.

AIM: To evaluate the contribution of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms to the risk of esophageal cancer. METHODS: Nineteen articles were included by searching MEDLINE, EMBASE and the Chinese Biomedical Database, 13 on ADH1B and 18 on ALDH2. We performed a meta-analysis of case-control studies including 13 studies on ADH1B (cases/controls: 2390/7100) and 18 studies on ALDH2 (2631/6030). RESULTS: The crude odds ratio [OR (95% confidence interval)] was 2.91 (2.04-4.14) for ADH1B*1/*1 (vs ADH1B*2/*2) and 1.32 (1.17-1.49) for ADH1B*1/*2. The crude OR for ALDH2*1/*2 (vs ALDH2*1/*1) was 2.52 (1.76-3.61). ADH1B*1/*1 increased the risk of esophageal cancer among never/rare [1.56 (0.93-2.61)], moderate [2.71 (1.37-5.35)], and heavy drinkers [3.22 (2.27-4.57)]. ADH1B*1/*2 was associated with a modest risk among moderate drinkers [1.43 (1.09-1.87)]. ALDH2*1/*2 increased the risk among never/rare [1.28 (0.91-1.80)], moderate [3.12 (1.95-5.01)], and heavy [7.12 (4.67-10.86)] drinkers, and among ex-drinkers [5.64 (1.57-20.25)]. ALDH2*2/*2 increased the risk among drinkers [4.42 (1.72-11.36)]. ADH1B*1/*1 plus ALDH2*1/*2 was associated with the highest risk for heavy drinkers [12.45 (2.9-53.46)]. The results of the meta-regression analysis showed that the effects of ADH1B*1/*1 and ALDH2*1/*2 increased with the level of alcohol consumption. ALDH2*1/*2 was associated with a high risk among Taiwan Chinese and Japanese drinkers, as opposed to a moderate risk among drinkers in high-incidence regions of Mainland China. ADH1B*1/*1 in heavy drinkers and ALDH2*1/*2 in moderate-to-heavy drinkers was associated with similarly high risk among both men and women. CONCLUSION: ADH1B/ALDH2 genotypes affect the risk of esophageal cancer, and the risk is modified by alcohol consumption, ethnicity, and gender.

The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers.We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before.The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes.The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner from nonalcoholics, and clear effects of ADH1B genotype and less clear effects of ALDH2 were observed in the alcoholics. Alterations in alcohol metabolism as a result of alcoholism may modify the gene effects, and these findings provide some clues in regard to associations between the genotypes and the risks of alcoholism and UADT cancer.

Background: The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers. Methods: We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before. Results: The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes. Conclusions: The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner from nonalcoholics, and clear effects of ADH1B genotype and less clear effects of ALDH2 were observed in the alcoholics. Alterations in alcohol metabolism as a result of alcoholism may modify the gene effects, and these findings provide some clues in regard to associations between the genotypes and the risks of alcoholism and UADT cancer.

Malnutrition and emaciation in alcoholics is associated with various alcoholism-related diseases, including Wernicke's encephalopathy, aero-digestive tract cancer, and serious metabolic disorders. We used a self-administered questionnaire survey for structured dietary habit screening to evaluate the dietary profiles of 467 Japanese alcoholic men aged 40 years or over and their relationship to body mass index (BMI). Their average daily ethanol consumption was 119 +/- 65 g (845 +/- 463 kcal). The survey showed that 50.5% of the subjects consumed three meals a day; 32.8%, two meals; 12.2%, one meal; and 4.5% rarely ate. The meals mainly consisted of carbohydrates and protein, with few vegetables. Daily alcohol consumption was inversely correlated with the frequency of meals, drinking milk, and consuming confectionery. The subjects who lived with their family (72.8%) consumed more meals than the subjects liv- ing alone. After excluding 22 subjects with leg edema or ascites, the average BMI was 21.3 +/- 3.2. The group with the lowest BMI values (18.5) accounted for 19.3% of the subjects, and those with the highest BMI values (or = 25) accounted for 11.5%. A multivariate stepwise logistic analysis showed that BMI increased 0.15 per 22 g ethanol consumed daily and decreased 0.03 per + 10 cigarettes smoked daily, 0.43 per decrease by one in daily frequency of meals, and 0.54 per category (daily, occasionally, rarely, seldom) of milk consumption. The likelihood of a low BMI18.5 was significantly and independently associated with smoking [OR (95%CI) =1.24 (1.02-1.51) per +10 cigarettes] and with intake of seafood [0.62 (0.41-0.94) per +1 category], milk [1.52 (1.16-2.00) per +1 category] and green and yellow vegetables [1.52 (1.05-2.21) per +1 category]. Intervention in regard to diet as well as drinking is important to preventing malnutrition and emaciation in alcoholics.

The location of waist circumference (WC) measurement differs among diagnostic guidelines for the metabolic syndrome. The present study examined which of four WC measurements was associated most strongly with the clustering of metabolic risk factors in cross-sectional study. The subjects comprised 1,140 Japanese employees, aged 20-70 years, who underwent health examinations in 2007 and 2008. WC was measured at (i) the narrowest part of the waist, (ii) midway between the lowest rib and the iliac crest, (iii) the umbilical level, and (iv) immediately above the iliac crest. A receiver operator characteristic (ROC) curve was used to assess the ability of each WC measurement to predict the presence of two or more other components of the metabolic syndrome, as defined by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) in 2005. Multiple risk factors were seen in 43.0% of the men and 12.9% of the women. The minimum and maximum WC measurements differed by 3.9 cm among the men and 12.6 cm among the women. The areas under the curve examining the ability of the four WC measurements to predict the clustering of multiple risk factors were similar. If the same WC cutoff value was applied, the prevalence of the metabolic syndrome changed considerably according to the site of WC measurement. The four WC measurements had similar screening abilities. Given the differences in the WC values according to the site of measurement, WC must be measured at the site specified by each diagnostic guideline.

After determining the normal ranges of serum high-density lipoprotein cholesterol levels, correlates of HDL-cholesterol were analysed in a sample of 1, 283 males and 2, 123 females aged 40 years and older in an agricultural area of Shibata City, Niigata Prefecture. The distribution of serum HDL-cholesterol was nearly a log-scale normal distribution curve. The median and the lower and upper normal limits were calculated theoretically and the median values were :40-49 age group, 51.9 mg/100 ml for males and 52.5 mg/100 ml for females ; 50-59 age group, 52.5 and 51.4; 60-69 age group, 51.4 and 49.4; over 70 age group, 49.4 and 47.9. There was almost no difference in HDL-cholesterol levels between both sexes. This was explained as possibly due to alcohol intake raising HDL-cholesterol levels in males. There was a positive association of HDL-cholesterol levels with reported amount of alcohol intake in males. Inverse relationships were found between serum HDL-cholesterol levels and obesity in any age group for both sexes. An inverse correlation between percent energy contribution by carbohydrate and HDL-cholesterol was observed in males. Caloric intake was positively correlated to HDL-cholesterol in females.

In order to improve population-based approaches in communities to extend healthy life expectancy of our population in the 21st century, it is essential to identify characteristics and risks thoroughly. This study assessed associations of dietary intake and health behavior with mortality from cancer, cardiovascular diseases, and all-causes in Japan at the prefectural level.By prefecture and sex, we calculated age-adjusted means for BMI, step counts, and nutrient and food intakes, as well as age-adjusted prevalence of smoking and alcohol drinking habits, using datasets of the 2001-05 National Health and Nutrition Survey. Age-adjusted total mortality rates (per 100,000 population), as well as cancer and cardiovascular mortality rates were obtained from Vital Statistics (2007). Multivariate stepwise regression analysis was used to compute partial correlation coefficients.In regard to BMI, mortality from myocardial infarction and cerebral hemorrhage showed significant positive correlations in both males and females, but significant negative correlations with mortality from stomach cancer in both sexes. The sodium chloride equivalent (salt) was positively correlated with mortality from cerebral hemorrhage in both males and females. In males, salt was also positively correlated with total mortality. In females, salt was also positively correlated with mortality from cerebral infarction and all types of stroke. Alcohol drinking was positively correlated with mortality from esophageal cancer in both genders and from cerebral infarction in males. Several other nutrients and food groups, as well as physical activity, were also associated with mortality risk.Although this study is an ecological analysis, these findings highlight some factors of public health importance.

The effects of short- or long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) on the colon have not been well characterized. We assessed the risk of developing colonic mucosal lesions according to the duration of exposure to NSAIDs: short-term and/or long-term use.A case-controlled study was performed by reviewing medical records for endoscopic findings, underlying disease, pre-endoscopic symptoms, category of NSAIDs used and duration of use. The patients underwent colonoscopy between January and October 2004, and 75 colitis cases and 1801 non-colitis controls were identified. The prevalence of NSAID use was compared between the cases and controls. The age- and sex- adjusted odds ratios (OR) were estimated using multiple logistic regression models.NSAIDs had been used in colitis cases and non-colitis controls for over six months in 20.0% and 12.7%, and for one week in 4.0% and 2.1%. Overall 76.0% and 85.2% had not received NSAIDs. The adjusted OR (95% confidence interval) for colonic mucosal lesions with short- and long term NSAID administration combined vs. non-use was 2.04 (1.16-3.61). When determined separately for short- and long-term NSAID users, the adjusted ORs were 1.48 (0.42-5.25) and 2.21 (1.19-4.11), compared to non-users. These values signify a trend toward an increased frequency of colonic mucosal lesions with longer use of NSAIDs (P=0.011 for trend).Long-term use of NSAIDs increased the risk of colonic mucosal lesions, suggesting that NSAIDs may contribute to the pathogenesis of colonic ulcer or colitis.

Background Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up. Methods Subjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables. Results The GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91). Conclusion The homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.

Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD.In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals.Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms.Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores.