Healthy Japanese Population Research Articles

Relationship between Alcohol Consumption and Serum Adiponectin Levels: The Takahata Study—A Cross-Sectional Study of a Healthy Japanese Population

The relationship between alcohol consumption and serum adiponectin levels has not been fully explored in an Asian population. Our goal was to determine whether alcohol consumption is associated with a change in adiponectin levels in a healthy Japanese population. This was a cross-sectional study. Subjects were recruited from participants in a health check-up program. This study included 2932 subjects (1306 men and 1626 women). The effects of total weekly or daily volume of ethanol intake on serum adiponectin levels were evaluated. In addition, the correlation of clinical traits with serum adiponectin levels was examined. A multivariate regression model was used to control for possible confounding factors. Alcohol consumption was weakly correlated with decreased serum adiponectin levels in men [Spearman's ordered correlation coefficient (rs=-0.141; P<0.001]; an even weaker correlation was seen in women (rs=-0.055; P=0.025). Multivariate analysis demonstrated that alcohol consumption was independently associated with hypoadiponectinemia. In contrast to reports from the United States and Europe among White and Black subjects, our study demonstrated an inverse association between alcohol intake and serum adiponectin levels in Asian subjects, suggesting ethnic differences in the effects of alcohol consumption on serum adiponectin levels.

Influence of dental occlusion on physical fitness decline in a healthy Japanese elderly population

The aim of this study was to clarify the relationship between dental occlusion and physical fitness by a longitudinal survey. A sample of 348 subjects (171 men and 177 women) aged 71 was investigated by Eichner index (EI) as an occlusal condition (Class A: no loss; Class B: partial loss; Class C: complete loss) and five types of physical fitness tests and were re-examined 8 years later. The upper 50% were sampled to analyze the correlation between each physical fitness decline and the EI at the baseline by logistic regression models. Logistic regression analyses revealed that leg extensor power (Class B vs. Class A; odds ratio = OR = 4.61, p = 0.010) and one-leg standing time with eyes open (Class C vs. Class A; OR = 4.27, p = 0.031) showed significant correlations with the EI at the baseline. In this study, partial or complete loss of occlusion was associated with a decline in leg extensor power or a decrease in one-leg standing time with eyes open. These findings suggest that maintenance of dental occlusion may prevent a decrease in activities of daily living in the elderly.

Relationship between Habit of Cigarette Smoking and Airflow Limitation in Healthy Japanese Individuals: The Takahata Study

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation. The prevalence of airflow limitation in Japan is 10.9% (16.4% of males and 5.0% of females). Cigarette smoking is well known as a major cause of COPD. However, few epidemiological studies have evaluated the effects of cigarette smoking on pulmonary function in healthy subjects. Subjects aged 40 years or older (n=2,917), who had participated in a community-based annual health check in Takahata, Japan, from 2004 through 2005, were enrolled in the study. The smoking histories of these subjects were investigated using a self-reported questionnaire. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), and forced expiratory flow at 25-75% of FVC (FEF(25-75)) were measured by standard procedures using spirometric machines. There were 554 current smokers (18.6%) and 403 former smokers (13.8%). The prevalence of airflow limitation defined by FEV(1)/FVC <0.7 in this population was 10.6%, and prevalence of airflow limitation defined by 5th percentile lower limit of normal was 6.4%. In smokers, percent predicted values of measured spirometric parameters (%FVC, %FEV(1) and %FEF(25-75)) decreased significantly with age, except for male %FVC. Also, percent predicted values of measured spirometric parameters decreased significantly with increasing pack-years, except for female %FEF(25-75). Cigarette smoking increased the prevalence and severity of airflow limitation. It is concluded that cigarette smoking increases the risk of airflow limitation in a healthy Japanese population.

Reference Ranges for Exhaled Nitric Oxide Fraction in Healthy Japanese Adult Population

The measurement of the exhaled nitric oxide fraction (FE(NO)) is proposed as a useful marker of airway inflammation. In healthy adults, there have been a few studies of the reference ranges for FE(NO) in Caucasians. A community study in other regions may reveal any possible ethnic differences in the FE(NO) levels. A total of 240 healthy adults aged between 18 to 74 years were recruited from four medical centers in Japan. Current smokers and subjects having a history of atopic disease were not included. FE(NO) was measured using an online electrochemical nitric oxide analyzer according to the current guidelines. The reference ranges for FE(NO) were estimated using two different statistical methods recommended by International Federation of Clinical Chemistry and Laboratory Medicine. The mean FE(NO) was 16.9 ppb (parts per billion) with a 95% prediction interval (2.5 to 97.5 percentiles) of 6.5 to 35.0 ppb in healthy Japanese adults. Normality assumptions were met for the logarithm-transformed FE(NO). The geometric mean FE(NO) was 15.4 ppb with a mean ± two standard deviations of 6.5 to 36.8 ppb. Age, gender, height, and past smoking history were not associated with the FE(NO) levels. The reference ranges for FE(NO) in healthy Japanese adults were similar to those of Caucasians. It seems reasonable that the upper limit of FE(NO) for healthy adults should be set at approximately 36.0 ppb irrespective of ethnic differences.

Examination of useful items for the assessment of fall risk in the community-dwelling elderly Japanese population

The aim of this study was to select useful items for assessing fall risk in healthy elderly Japanese individuals. A total of 965 healthy elderly Japanese subjects aged ≥60years (349 males 70.4±7.1years, 616 females 69.9±7.1years) participated in this study. Of these, 16.6% had suffered from a previous fall. We assumed five fall risk factors: symptoms of falling, physical function, disease and physical symptoms, environment, and behavior and character. Eighty-six items were selected to represent these factors. To confirm the component items for each risk factor, we performed factor analysis (principle factor solution and varimax rotation). The high-fall risk response rate was also calculated for each item, and significant differences in this rate were examined between groups of those who had and not had experienced a fall. Useful items were selected using the following criteria: (1) items showing a significant difference in high fall risk response rate between faller and non-faller groups were selected as useful items; (2) items showing low factor loading (<0.4) for any factor were deleted as inappropriate items; (3) the top two items showing a greater amount of the difference in high fall risk response rate among the representative items for each factor. A total of 50 items were selected from each fall risk factor (symptoms of falling, 3 items; physical function, 22 items; disease and physical symptom, 13 items; environment, 4 items; behavior and character, 8 items). Based on our results, the selected items can comprehensively assess the fall risk of a healthy elderly Japanese population. In addition, the assessment items for physical function comprised items of different levels of difficulty, and these are able to gradually and comprehensively assess physical function.

Periodontitis-associated up-regulation of systemic inflammatory mediator level may increase the risk of coronary heart disease

Although an elevation in the concentration of high-sensitivity C-reactive protein (hs-CRP) as a result of periodontal infection may account for an increased risk of developing coronary heart disease (CHD), the effect of periodontal infection on the level of hs-CRP in an otherwise healthy Japanese population has not yet been reported. The aim of the present study was to confirm, on a larger scale, our previous pilot study findings that both chronic periodontitis and subsequent periodontal treatment alter the serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). The concentrations of serum hs-CRP, IL-6 and TNF-alpha were measured in 78 periodontitis patients at baseline and at re-assessment, and in 40 periodontally healthy subjects at the time of examination. The concentrations of hs-CRP and IL-6 in the sera of periodontitis patients were significantly higher than those in control subjects. By contrast, the concentration of TNF-alpha was significantly lower in periodontitis patients than in control subjects. Whereas periodontal treatment decreased the levels of serum hs-CRP and IL-6, no such effect was observed for TNF-alpha. When the patients were subdivided into four groups according to their initial concentration of hs-CRP, only the CRP and IL-6 concentrations of the highest quartile group showed a significant reduction following periodontal treatment. No significant difference in the initial clinical parameters was observed in any quartile. Although periodontal infection does affect the concentration of hs-CRP and IL-6 in serum, a subgroup of patients exist who are highly susceptible to an increased risk of CHD associated with periodontitis, suggesting that there may be subjects who have an elevated risk of CHD independent of susceptibility to periodontal tissue destruction per se.

Abstract 6214: Comparison of Adiponectin Levels in Healthy Americans and Japanese: Results from Framingham and Fukuoka

Background and Objectives: Adiponectin is an adipocytokine with insulin-sensitizing and anti-atherosclerotic effects. Serum adiponectin levels have been reported to be negatively correlated with body weight and waist circumference (WC). Low plasma adiponectin levels are known to predispose to the development of insulin resistance and type 2 diabetes mellitus. Adiponectin levels may vary according to ethnic group. The aim of this study was to investigate potential differences in plasma adiponectin levels between Japanese and Americans. Methods: Subjects consisted of 2,060 healthy American male and female participants in exam 6 of the Framingham Offspring Study (mean age 57.0 ± 9.0 years, 57.4 ± 10.5 years, respectively), and 1131 healthy Japanese male and female participants in the Fukuoka Study (mean age 56.3 ± 5.5 years, 55.6 ± 5.4 years, respectively). Frozen plasma samples (at −80 degree C) from both studies were shipped to Tufts University, Boston. Plasma concentrations of direct LDL-C, fasting plasma glucose and adiponectin were measured using the same assay kits on the same machine (Hitachi 911) by the same staff. Anthropometric measurements including weight, height, body mass index (BMI) and WC, were also used in the analysis. Results: Plasma adiponectin levels were significantly and inversely correlated with BMI, WC, glucose, insulin, triglycerides, and systolic and diastolic blood pressure. Moreover adiponectin levels were significantly and positively correlated with HDL-C in both populations. Mean BMI and WC of Japanese men and women were significantly lower (23.8 kg/m 2 and 22.1 kg/m 2 , 86.0 cm and 78.7 cm, respectively) than in US men and women (28.2 kg/m 2 and 27.0 kg/m 2 , 100.4 cm and 92.8 cm, respectively) (all p&lt;0.05). However, mean adiponectin levels (± SD) in Japanese men and women were significantly lower (9.3 ± 4.5 micro g/mL and 14.7 ± 7.3 micro g/mL, respectively) than in US men and women (10.3 ± 5.2 micro g/mL and 16.3 ± 7.7 micro g/mL, respectively)(p&lt;0.05). Conclusion: Our data indicate a substantially lower prevalence of adiposity, but not higher adiponectin levels, in a healthy Japanese population as compared to an American population. The data indicate that population specific norms may have to be used for different ethnic groups.

The Relationship Between Job Stress and Urinary Cytokines in Healthy Nurses: A Cross-Sectional Study

Cytokines such as angiogenin (ANG) and interleukin (IL-8) have been shown to be related to depressive symptoms and inflammatory diseases like coronary heart disease. They may thus be used as stress biomarkers to identify and prevent health problems. To investigate the relationship between cytokines and nurses' job-related stress, levels of urinary ANG and IL-8 were measured in healthy female hospital nurses in Japan. The level of job-related stress of the subjects was evaluated using the Nursing Stress Scale (NSS), with the participants being classified into high- or low-stress groups for each subscale according to their scores. The participants' subjective psychological states were assessed using the Profile of Mood States--Short Form Japanese version (POMS-SFJ). Urinary ANG, IL-8, and cortisol levels and subjective psychological states for two groups were compared for each NSS subscale. The fatigue and depression scores of POMS-SFJ subscales in the present study were higher than those of the general healthy Japanese population. Based on the mean score of the combined participants, nurses were experiencing the highest stress related to the pressure of having responsibility for patients' life support care (PPLC). Nurses reporting high levels of stress related to PPLC and conflict with physicians had high levels of urinary ANG. Urinary ANG levels may thus be associated with high levels of job stress.

Normal Values of Echocardiographic Parameters in Relation to Age in a Healthy Japanese Population The JAMP Study

Normal values for echocardiographic measurements and the relationship between these parameters and age in a large Japanese population are still unknown. A total of 700 healthy Japanese aged 20-79 years underwent 2-dimensional and Doppler echocardiography at collaborating institutions. The respective mean values obtained in men and women were as follows: septal wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; posterior wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; left ventricular (LV) diastolic diameter, 4.8+/-0.4 and 4.4+/-0.3 cm; LV systolic diameter, 3.0+/-0.4 and 2.8+/-0.3 cm; LV diastolic volume, 93+/-20 and 74+/-17 ml; LV systolic volume, 33+/-20 and 25+/-7 ml; LV ejection fraction, 64+/-5 and 66+/-5%; maximum left atrial (LA) volume, 42+/-14 and 38+/-12 ml. Aortic root diameter, LV wall thickness, and LV mass slightly increased with age, whereas indexed LA volume did not vary with age. Diastolic parameters assessed by mitral inflow and mitral annular velocities declined with age, as previously reported. Normal values of echocardiographic measurements in a large Japanese population are reported for the first time; several systolic and diastolic parameters varied with age. These results provide important reference values that should be useful in routine clinical practice as well as in clinical trials.

Familial Mediterranean fever in three Japanese patients, and a comparison of the frequency of MEFV gene mutations in Japanese and Mediterranean populations

We report on three Japanese patients (two families) with familial Mediterranean fever (FMF), a rare disease in the Far East. Two of the patients (siblings with definite FMF) were heterozygous for both E148Q and M694I, and the remaining patient (with probable FMF and no family history of the disease) was heterozygous for both P369S and R408Q. Although the M694I mutation is less common among Mediterranean populations, it was present in 22 (76%) of 29 Japanese patients with FMF (previously reported cases). We therefore investigated the allele frequency of M694I in the healthy Japanese population, as well as other FMF-causing mutations in exon 10 (M680I, M694V, and V726A) and polymorphisms (E148Q, P369S, and R408Q) of the Mediterranean fever gene (MEFV). The allele frequencies of disease-causing mutations, even M694I, were <0.001. While those of E148Q, P369S, and R408Q were 0.23, 0.057, and 0.054, respectively. Because of the low allele frequencies of disease-causing mutations, FMF is an extremely rare disease among Japanese individuals. However, FMF is an important component of hereditary autoinflammatory syndrome, and a diagnosis of FMF is crucial for the choice of treatment, because of the benefit of colchicine therapy.

Safety of Dietary Conjugated Linoleic Acid (CLA) in a 12-weeks Trial in Healthy Overweight Japanese Male Volunteers

A study was conducted to investigate the short-term safety of dietary conjugated linoleic acid (CLA) in overweight Japanese male volunteers. The study design was a randomized, double-blind placebo-controlled trial including 60 healthy overweight volunteers (body mass index (BMI), 25 approximately 35 kg/m(2)). The subjects were randomly assigned to three groups: 5.4 g CLA-triacylglycerol (3.4 g as CLA), 10.8 g CLA-triacylglycerol (6.8 g as CLA) and placebo (10.8 g safflower oil) daily for 12 weeks. The CLA-triaclyglycerol contained 9c,11t- and 10t,12c-isomers at an equal proportion. The safety was evaluated by analyses of blood parameters and by clinical examinations at the baseline, and at 6 and 12 weeks, including vital signs and adverse effects. All subjects completed the study. The occurrence of adverse events tended to be higher in the CLA groups than in the placebo group, but all of the adverse events were mild to moderate, within normal ranges, and temporary. Serum aspartate aminotransferase (AST) activity did not differ significantly between the groups at 12 weeks, but in the high CLA group it was slightly increased from the baseline. Serum alanine aminotransferase (ALT) activity was higher in the high CLA group than in the placebo group after 12 weeks and was higher than at the baseline in both CLA groups. However, statistical analysis of the population of apparently healthy volunteers who had normal blood parameters at the baseline revealed that AST and ALT levels did not differ significantly among the 3 groups at 12 weeks. Moreover, no clinically significant changes in vital signs were observed in any of the groups. These results indicate that CLA at a dose of 3.4 g/day is a safe dietary level in healthy Japanese populations in terms of the parameters examined.

Sources of variation and reference intervals for serum cystatin C in a healthy Japanese adult population

To derive reference intervals (RIs) for cystatin C (CysC), we examined sources of variation in its serum concentration by multiple regression analysis. A total of 596 healthy subjects (30-75 years of age) who underwent an annual health check were chosen as candidate reference individuals who did not have any chronic illness requiring medication. Serum CysC was measured together with routine screening tests (basic clinical chemistry and complete blood count). Multivariate analysis revealed that CysC concentrations were higher in males by an average of 0.082 mg/L. Levels were positively associated with age (+0.047 mg/L for every 10 years), body fat (BF%) and cigarette smoking, and negatively associated with alcohol consumption. A subgroup analysis revealed that the gender difference was not significant for those over 50 years of age. RIs were determined using a "latent abnormal values exclusion method" involving deletion of individuals with two or more abnormal results in the screening tests. RIs were partitioned into three categories by age and gender: 0.60-0.95 mg/L for males aged 30-50 years; 0.55-0.84 mg/L for females aged 30-50 years; and 0.64-1.05 mg/L for all subjects aged 51-75 years. Creatinine levels showed little age-related change, but a conspicuous gender difference; they increased with body weight, but not with BF%. In interpreting serum CysC levels, BF%, cigarette smoking, and alcohol consumption may need to be considered, in addition to age and gender, as sources of variation.

Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia

This study investigated the relevance of the cytochrome P450 (CYP) 2D6 genotype to the adverse drug reactions (ADRs) of H1-antihistamines and the level of sedation. Japanese participants in a health screening program were asked to describe any past history of ADRs. Any subjects reporting ADRs induced by H1-antihistamines were then individually interviewed and defined as cases. Excessive daytime sleepiness, which had occurred in the cases as an H1-antihistamine-induced ADR, was assessed by the Epworth sleepiness scale (ESS), and an ESS score >or=12 was considered hypersomnia. CYP2D6*4, *5, *14, and *10 were genotyped by a panel of polymerase chain reaction techniques. Out of 2,074 participants, 100 cases (M:F = 37:63, mean age 51.9 +/- 9.2 years) were eligible for analysis. The most common etiological drug was chlorpheniramine, which is the most frequently used H1-antihistamine in Japan. CYP2D6*10 allele and genotypes were more frequently found in the cases than in the healthy Japanese population in a large study (P < 0.005 and P = 0.039, respectively), but no difference was observed in the null alleles and genotypes. The ESS scores in 75 cases (M:F=25:50) who had experienced excessive daytime sleepiness were 9.5 +/- 5.5 in men and 12.9 +/- 6.1 in women (P < 0.001, cases vs. 34 subjects without symptoms; P = 0.001 men vs. women). The occurrence of hypersomnia increased as the number of CYP2D6 mutant alleles increased (P = 0.045). The results suggest that the presence of the CYP2D6*10 allele is a risk factor for development of H1-antihistamine-induced ADRs in Japanese.

Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population

alpha(1A)-adrenergic receptor (alpha(1A)-AR) regulates the cardiac and peripheral vascular system through sympathetic activation, and alpha(2A)-AR and alpha(2C)-AR subtypes are essential for presynaptic feedback regulation of catecholamine release from the central and peripheral sympathetic nerve. Genetic variations in each human alpha-AR subtype gene have been identified and have been implicated in hypertension and cardiovascular disease. It is not yet clear whether these genetic variations actually have an effect on sympatho-vagal modulation. The aim of the present study was to evaluate the relation between the five representative genetic polymorphisms of alpha-AR subtypes (Arg347Cys of alpha(1A)-AR; C-1291G, Asn251Lys, and DraI RFLP of alpha(2A)-AR; and Del322-325 of alpha(2C)-AR) and autonomic nervous system (ANS) function in young and healthy Japanese males. One hundred forty-nine subjects were genotyped for each alpha-AR polymorphism, and underwent evaluation of ANS function by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. In a supine position, the alpha(1A)-AR 347Cys allele was significantly associated with lower HRV sympathetic index (normalized low frequency power [LF(%)] and LF:HF ratio) and higher HRV parasympathetic index [HF(%)]. Meanwhile, subjects with the alpha(2C)-AR Del322-325 allele had markedly higher LF(%) and LF:HF ratio and lower HF(%) than noncarriers. Thus, the alpha(1A)-AR and alpha(2C)-AR genetic variations influence sympatho-vagal balance even in young and healthy normotensive states, which could be postulated to constitute an intermediate phenotype for future pathological episodes of various ANS dysfunction-related diseases.

Identification of ADRA2A polymorphisms related to shear-mediated platelet function

α2A adrenergic receptor (ADRA2A) on platelets interacts with epinephrine, which has a key role in regulating platelet functions. There is familial clustering of inter-individual variations in the epinephrine-induced platelet aggregation, the molecular basis of which, however, has not been fully understood. In this study, we screened the sequence variations in the transcriptional region of ADRA2A gene and analyzed the relationship between the two common polymorphisms and platelet function using epinephrine/collagen cartridge in the platelet function analyzer-100 system ®, in a healthy Japanese male population ( n = 211). Among the identified 16 sequence variations including five novel variations, 1780GG genotype was associated with longer closure time which represents low platelet function under high shear-stress conditions ( p = 0.0478). We also observed enhanced effect of the combination of 1780GG and 2372AA genotypes on longer closure time ( p = 0.0319). These findings suggest that 1780A/G and 2372A/G polymorphisms are associated with platelet function in interactions with collagen/epinephrine.

Association of abdominal obesity with decreased serum levels of carotenoids in a healthy Japanese population

Few epidemiological studies have investigated the relationship between abdominal adiposity and serum levels of carotenoids. This study investigated the relationship between total and abdominal obesity and serum levels of carotenoids. Study population consisted of healthy Japanese males (n=192) and females (n=398) who attended a health examination screening (age: 49-86 years). Serum carotenoids were measured by high-performance liquid chromatography. Multiple logistic regression analysis was used to provide the multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) of obesity indices for low levels of serum carotenoids. In females, High waist circumference was associated with low levels of serum canthaxanthin (OR=2.00, 95% CI=1.26-3.19) and beta-carotene (BC) (OR=2.01, 95% CI=1.23-3.28). High waist hip ratio was also associated with low levels of serum alpha- carotene and BC (OR=2.44, 95% CI=1.49-4.03, and OR =1.97, 95% CI=1.20-3.28, respectively). Similar results were obtained when body mass index was added to confounding factors. In males, however, there were no significant associations between obesity indices and serum levels of carotenoids. Our results suggest that abdominal fat accumulation is associated with oxidative stress as determined by low levels of serum carotenoids in females. In males, further study excluding the effect of strong confounding factors, including smoking, is needed.

Physical Activity Level among Healthy Japanese Adults Estimated by the Doubly Labeled Water Method

Background: Measurements of total energy expenditure (TEE) and the development of simple questionnaire to determine the physical activity level are required for estimation of the energy requirement in dietary reference intakes for Japanese. PURPOSE: To measure TEE among healthy Japanese adults, and evaluate the predictability of the International Physical Activity Questionnaire (IPAQ) and the classification of intensity of daily activity (IDA) used in the National Nutrition Survey in Japan. METHODS: Healthy Japanese men (n=74) and women (n=76) were recruited from four areas in Japan. TEE was measured during a 14-day period with the doubly labeled water. Physical activity status was assessed using the short-version of IPAQ and the IDA in the last 7 days. RESULTS: TEE and PAL (TEE/basal metabolic rate) were 2,619+406 and 1.74+0.22 for men and 2,032+316 and 1.71+0.22 for women, respectively. There was no significant difference by sex, age and area. IPAQ and IDA distinguished significantly most active groups from other groups. However, PAL was not significantly different among other less active groups. CONCLUSIONS: The average PAL of healthy Japanese population is around 1.7. Highly active population can be identified by simple questionnaires. However, IPAQ and IDA could not classify the sedentary and moderate active subjects.

Gene–environmental interactions between alcohol-drinking behavior and ALDH2 and CYP2E1 polymorphisms and their impact on micronuclei frequency in human lymphocytes

Ethanol is converted to acetaldehyde by alcohol dehydrogenase (ADH), cytochrome p4502E1 (CYP2E1) and catalase. This metabolite is then detoxified by aldehyde dehydrogenase 2 (ALDH2), a key enzyme in the elimination of acetaldehyde, via further oxidation to acetic acid. The toxic effects of acetaldehyde are well documented and may be partially mediated by genotoxic damage. In the present study, we investigated the effects of alcohol-drinking behavior and genetic polymorphisms in two different genes (ALDH2 and CYP2E1) on the micronuclei (MN) frequency in 248 healthy Japanese men. Genotyping was performed by PCR–RFLP analysis. The ALDH2 variant (deficient type) was significantly associated with an increased MN frequency in subjects drinking more than three times/wk, while habitual drinkers with wild-type CYP2E1 also had a significantly increased MN frequency. Furthermore, when the subjects were divided into eight groups according to their drinking frequency and genotypes of ALDH2 and CYP2E1, we found that habitual drinkers with homozygous CYP2E1 *1/ *1 and heterozygous ALDH2 *1/ *2 or homozygous ALDH2 *2/ *2 showed the highest mean MN frequency. In the present study, we found clear associations among ALDH2 and CYP2E1 gene polymorphisms, alcohol-drinking behavior and genotoxic effects in a healthy Japanese population. Therefore, analysis of the polymorphisms of alcohol-metabolizing enzymes may lead to elucidation of the mechanism(s) for individual susceptibilities to the toxicity of ethanol metabolites.

De Novo Age-related Retinal Disease and Intraocular-pressure Changes During a 10-year Period in a Japanese Adult Population

To determine the proportion of age-related ophthalmologic diseases discovered in a healthy Japanese adult population, as well as to evaluate the age-related changes in intraocular pressure (IOP) in this population during a 10-year period. Ophthalmologic surveys were conducted in 1988 and 1998 at Tamaho-cho in Yamanashi Prefecture. The target population of the first survey was 1389 subjects over 40 years of age, and of these, 1250 subjects (473 men and 777 women) participated in the survey. Their mean age was 57.8 +/- 11.9 years. Of these 1250 subjects, 245 subjects participated in the second ophthalmologic survey in 1998. The cases of glaucoma or age-related ophthalmologic diseases developing over the intervening 10-year period were determined among the subjects who had been diagnosed with no ophthalmologic abnormalities in the 1988 survey. We also compared the IOP values of the 219 subjects who were diagnosed with no ophthalmologic abnormalities in either the 1988 or the 1998 survey. The number of cases in the 1998 survey with newly discovered ocular diseases were as follows: two cases (0.82%) of normal-tension glaucoma, two cases (0.82%) of epiretinal membrane, one case (0.41%) of age-related macular degeneration, one case (0.41%) of angle-closure glaucoma, and one case (0.41%) of branch retinal vein occlusion. The mean IOP of the 219 subjects diagnosed with no ophthalmic abnormalities in either survey was 13.88 +/- 3.04 mmHg in 1988, which declined significantly to 13.16 +/- 2.75 mmHg in 1998 (P < 0.0001). The 10-year follow-up of the 245 subjects participating in both surveys showed one or two de novo cases of age-related macular degeneration, epiretinal membrane, branch retinal vein occlusion, normal-tension glaucoma, or angle-closure glaucoma. IOP was found to decline significantly with age.

Prevalence of antibodies against Simkania negevensis in a healthy Japanese population determined by the microimmunofluorescence test

Simkania negevensis has been associated with bronchiolitis in infants and community-acquired pneumonia in adults. Reports of exposure to this microorganism are only available from Israel, North America and Western Europe. Currently, no standard method for diagnosis of S. negevensis infection has been established nor have prevalence rates been shown in Japan. For the first time we demonstrated the ability of the microimmunofluorescence (MIF) test to detect S. negevensis-specific immunoglobulin G and exposure to S. negevensis in Japan. The positive rate in healthy volunteers was 4.3% (25/588), with rates increasing with age. Results indicate the usefulness of the MIF test as a serological method for detecting S. negevensis-specific antibodies. A standard serological test for infection with S. negevensis is needed.