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Purpose We examined the associations between lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS) using a case-control study in Aichi Prefecture, Japan. Methods The study comprised 183 ALS patients diagnosed by the El Escorial World Federation of Neurology criteria as well as 366 gender- and age-matched controls randomly selected from the general population with the use of the basic register of residents. Detailed information on lifestyle factors was obtained through a mailed self-administered questionnaire. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Results Vigorous physical activity, self reported stress, a type A behavior pattern, and less frequent intakes of green-yellow vegetables were significantly associated with increased risk of ALS, whereas smoking and drinking habits were not. The greatest effect on risk for ALS was posed by the combination of a type A behavior pattern and less frequent intakes of green-yellow vegetables (adjusted OR, 11.2; 95% CI, 3.8 to 33.0). Conclusion These data suggested that imbalances between excessive productions of oxidants as patient-specific factors and a diminished or missing antioxidant defense system in motor neurons may increase the risk of ALS.

STUDY DESIGN A sex- and age-matched case-control study with genotyping of the FokI variant of the vitamin D receptor gene (VDR) was carried out. OBJECTIVES To facilitate the early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament (OPLL) of the spine, we analyzed the FokI variant of VDR and past body mass indexes, histories of past illness, family history, and body pliability along with lifestyle factors. SUMMARY OF BACKGROUND DATA Many possible genetic and environmental risk factors for OPLL have been suggested, including male sex, high body mass index, diabetes mellitus, trauma, hormonal imbalance, and dietary and sleeping habits and genetic variants. METHODS Both a self-administered questionnaire and whole blood samples were obtained from 63 patients with OPLL and 126 sex-, age-, and hospital-matched controls free of backbone diseases were randomly selected from hospital patients. VDR genotyping was carried out using PCR-RFLP methods. After univariate analysis, multivariate and subgroup analyses according to the VDR genotype was applied to clarify the confounding relationship between VDR genotype and other possible risk factors. RESULTS A multivariate analysis revealed that the VDR FF genotype, family history of myocardial infarction, high body mass index at age 40, long working hours, and working with night shift to be independent potent risk factors for OPLL. CONCLUSION The risk of developing OPLL may possibly be reduced gradually and effectively by removing or minimizing the effect of such lifestyle factors one at a time through targeted preventive intervention.

Only a few human studies have reported the relationship between dietary factors and the risk of amyotrophic lateral sclerosis (ALS). We therefore analyzed the relationship between macronutrients (carbohydrate, protein and fat) and the risk of ALS using a case-control study in Japan. The study comprised 153 ALS patients diagnosed by the El Escorial World Federation of Neurology criteria, and 306 gender- and age- matched controls randomly selected from the general population. A self-administered food frequency questionnaire was used to estimate pre-illness intakes of food groups and nutrients. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). A high intake of carbohydrate was significantly associated with an increased risk of ALS (adjusted OR = 2.14, 95% CI 1.05-4.36; the highest versus the lowest tertile). ORs for the second and third tertile of total fat were 0.57 and 0.41 (95% CI 0.21-0.80), respectively. ORs for the highest tertile of intake versus the lowest were 0.41 (95% CI 0.21-0.80) for total fat, 0.30 (95% CI 0.16-0.5) for saturated fatty acids (SFAs), 0.35 (95% CI 0.18-0.69) for monounsaturated fatty acids (MUFAs) and 0.58 (95%CI 0.40-0.96) for polyunsaturated fatty acids (PUFAs). Our findings suggest that high intakes of carbohydrate and low intakes of fat and some kinds of fatty acids may, when combined, increased the risk of ALS.

Objectives: A few epidemiological studies have indicated that a patient's past medical history may contribute to the risk of developing idiopathic pulmonary fibrosis (IPF). A relationship between a history of selected disorders and the risk of IPF was assessed in a multicentre hospital-based case-control study in Japan. Methodology: Included in the study were 104 patients of IPF, aged 40 years or over, who had been diagnosed within the previous 2 years, in accordance with the most recent criteria. Control subjects, aged 40 years or over, consisted of 56 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with the common cold. Adjustment was made for age, gender, region, pack-years of smoking, employment status, occupational exposure and BMI. Results: Medical histories of hypertension, hyperlipidaemia, coronary heart disease, diabetes mellitus, hepatitis C virus infection, tuberculosis, asthma, atopic dermatitis and allergic rhinitis were not statistically significantly associated with the risk of IPF, although cases were more likely to have suffered from allergic rhinitis and less likely to have been asthmatics than control subjects. Having a child with a history of allergic rhinitis, but not of asthma or atopic dermatitis, was significantly related to an increased risk of IPF. Conclusions: These findings suggest that a genetic predisposition to allergic rhinitis may be associated with an increased risk of IPF.

To evaluate the role of dietary factors in the etiology of inflammatory bowel disease (IBD), we conducted a multicenter hospital-based case-control study in a Japanese population. Cases were IBD patients aged 15 to 34 years [ulcerative colitis (UC) 111 patients; Crohn's disease (CD) 128 patients] within 3 years after diagnosis in 13 hospitals. One control subject was recruited for each case who was matched for sex, age, and hospital. A semiquantitative food frequency questionnaire was used to estimate preillness intakes of food groups and nutrients. All the available control subjects (n = 219) were pooled, and unconditional logistic models were applied to calculate odds ratios (ORs). In the food groups, a higher consumption of sweets was positively associated with UC risk [OR for the highest versus lowest quartile, 2.86; 95% confidence interval (CI), 1.24 to 6.57], whereas the consumption of sugars and sweeteners (OR, 2.12; 95% CI, 1.08 to 4.17), sweets (OR, 2.83; 95% CI, 1.38 to 5.83), fats and oils (OR, 2.64; 95% CI, 1.29 to 5.39), and fish and shellfish (OR, 2.41; 95% CI, 1.18-4.89) were positively associated with CD risk. In respect to nutrients, the intake of vitamin C (OR, 0.45; 95% CI, 0.21 to 0.99) was negatively related to UC risk, while the intake of total fat (OR, 2.86; 95% CI, 1.39 to 5.90), monounsaturated fatty acids (OR, 2.49; 95% CI, 1.23 to 5.03) and polyunsaturated fatty acids (OR, 2.31; 95% CI, 1.12 to 4.79), vitamin E (OR, 3.23; 95% CI, 1.45 to 7.17), and n-3 (OR, 3.24; 95% CI, 1.52 to 6.88) and n-6 fatty acids (OR, 2.57; 95% CI, 1.24 to 5.32) was positively associated with CD risk. Although this study suffers from the shortcoming of recall bias, which is inherent in most retrospective studies (prospective studies are warranted to confirm the associations between diet and IBD risk), the present findings suggest the importance of dietary factors for IBD prevention.

The relation between dietary habits and the risk of ossification of the posterior longitudinal ligaments of the spine (OPLL) was investigated in a case-control study conducted in Japan from 1998 to 2001. Prevalent OPLL cases (n = 69) were identified and individually matched by age and sex with community controls (n = 138) randomly selected from the general population in Hokkaido. A self-administered food-frequency questionnaire was used to assess habitual dietary intake. The odds ratio (OR) and its 95% confidence interval (CI) were estimated, using conditional logistic regression models to compute the OR adjusted for a history of diabetes mellitus. We found that frequent consumption of pickles (salted products) was significantly associated with an increased risk of OPLL, with an adjusted OR of 1.6 (95% CI, 1.1 to 2.2). The adjusted OR for nondaily consumers of rice was 3.0 (95% CI, 2.4 to 3.7). Frequent consumption of chicken (adjusted OR, 0.5; 95% CI, 0.3 to 0.98) and soy foods (adjusted OR, 0.4; 95% CI, 0.2 to 0.7) was significantly associated with a decreased risk of OPLL. Our findings suggest that dietary habits may constitute independent risk factors for OPLL. Further studies will be needed to prospectively determine the relationship between dietary habits and OPLL risk.

Study design A sex- and age-matched case-control study was carried out. Objectives To facilitate early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament of the spine, the authors analyzed histories of past illness, past body mass indexes, and body pliableness by nature, adjusted for other factors considered to be risk factors. Summary of background data The cause of ossification of the posterior longitudinal ligament of the spine has not yet been elucidated in detail, although many possible causative factors have been suggested, including gender, diabetes mellitus, trauma, hormonal imbalance, and dietary habits. Methods A self-administered questionnaire was obtained from 69 patients with ossification of the posterior longitudinal ligament of the spine and 138 sex- and age-matched control participants who were free of spinal disease, randomly selected from participants in a health checkup in a town. After univariate analysis, a stepwise method was applied to select significant factors in multivariate analysis. Results A multivariate analysis revealed that the following three indicators were independent potent risk factors for ossification of the posterior longitudinal ligament of the spine: history of diabetes mellitus, history of lumbago, and maximum body mass index before manifestation > or =25, after adjustment for other possible lifestyle risk factors. Conclusion Excessive weight gain between 20 and 40 years of age, diabetes mellitus, and lumbago were found to be independent risk factors for ossification of the posterior longitudinal ligament of the spine. Follow-up studies, including the addition of hospital-based control participants and analysis of genetic polymorphisms, will be needed in the future.

To clarify the roles of vitamin K (VK) in the pancreas, twice oral, glucose tolerance tests were examined in 12 healthy young male volunteers before and after 1 week of VK tablet intake. Blood were collected by venipucture at 0, 30 and 120 min after 75 g oral glucose loading. They then took VK tablets (90 mg/d of menaquinone-4) for 1 week, and the second glucose tolerance test was examined. The subjects were divided into three groups by serum descarboxy prothrombin (DP) levels; four of lowest DP (L-DP), middle of DP (M-DP) and highest DP (H-DP) levels. They were compared by one-factor analysis of variance and Scheffè's F (group differences) and paired t -test (the effects of 1 week of VK intake). Age, body mass index and glucose status [plasma glucose (PG) and immunoreactive insulin (IRI), hemoglobin-Alc, fructosamine] of all groups were almost the same, but the IRI of the H-DP group was higher than that of the other groups at 120 min after the glucose loading (mean+/-SEM; L; 10.6+/-0.9, M-; 17.5+/-4.2, H-; 40.4+/-6.0 microU/ml). One week of VK intake tended to decrease the plasma DP levels of all groups and significantly reduced IRI of the H-DP at 120 min by half (before; 40.4+/-6.0 vs after: 18.4+/-4.6 microU/ml). The IRI/pG ratio in areas under the curve (AUC) of H-DP from 0 to 120 min after the loading was significantly decreased by 1 week of VK tablet intake (before: 31.0+/-7.4 vs after: 20/1+/-3.8 microU/g). These results suggested that there may be some relationship between pharmacological dose of vitamin K and insulin response.

To clarify the effect of farm work time on blood pressure and blood cells status, 27 male and 29 female aged healthy farmers (70-86 years old) were asked weekly farm work times, measured forearm blood pressures and collected venous bloods. They were categorized by sex, by age (70-79 y and 80- y) and by weekly farm work hours (0; no-N, s 28; moderate-M, >28 h/w; heavy farm work time group H-FW). Systolic blood pressures of male and female H-FW were significantly lower than those of MFW, and diastolic blood pressures, hemoglobin concentrations, hematocrit values, mean cell volumes and mean cell hemoglobin concentrations of red blood cells showed same tendency in 70- 79 y. White blood cell numbers also tended to decrease by farm work in 80- y males and females, and platelet numbers tended to be high in females and M-FW. These results suggested that farm work time effects on blood pressure, anemic tendency, and blood cells status.

The effects of daily eicosapentaenoic acid (EPA) intake and physical activity on high-density lipoprotein (HDL) subfraction, which may be an index of health status, were examined. The HDL subfraction, triglyceride and T-chol levels in the serum of 10 male volunteers aged 20–25 were examined before, immediately after and 1 h after being subjected to a physical load by bicycle ergometer at 90 W for 20 min. Subjects were then given 1.25 g EPA/day for 2 weeks, and the above test was repeated. By EPA intake, the distribution of HDL3b and 3c decreased significantly by 16.8 and 15.3%, respectively, and that of 2b increased significantly by 17.9%. The rate of change of subfraction of the 29th part (2b) of 30 parts in the total range of HDL increased by 67%, and decreased by 47% in 7th part (3c). By physical load, the distribution of HDL2a increased significantly by 15.4%, while 3b tended to decrease. By physical load after EPA intake, the distribution of 2a decreased significantly by 9.7%, and those of 3b and 3c increased significantly by 20.5 and 5.4%, respectively, and that of the 7th part (3c) increased by 37%. Thus, the physical load after EPA intake is effective to prevent arteriosclerosis as increasing the rate of change of HDL3c and as showing the longevity pattern of the HDL subfraction. Concentration of TG in a modal HDL pattern group increased by 95% after EPA intake, but that of a bimodal group did not show any change. HDL-cholesterol level in the bimodal group was higher than that in the modal group, especially after EPA intake. Two type III subjects changed to type IV by the load and the EPA intake, respectively. Thus, it seemed that the transformation from a modal pattern to a bimodal pattern by a certain lifestyle, especially regular physical activity and proper food intake, is a very important trial for the prevention of cerebrovascular diseases.

Twenty male volunteers 20-25 years old were examined to determine their serum concentrations of interleukin-6 (IL-6), acute phase proteins and lipids before, immediately after and one hour after a load of 90 watts for 20 minutes using a Monark ergometer, and the same parameters were reexamined after eicosapentaenoic acid (EPA) intake of 1.125 g/day for 2 weeks. By EPA intake, EPA level of the membranes of red blood cells increased significantly by 75.6% and docosahexanoic acid (DHA) by 53.8%. The IL-6 level increased significantly by 17% and C-reactive protein (CRP) by 11.7%, but fibrinogen (Fbg) decreased by 9.6%. After EPA intake, at one hour after the load, the change rate of IL-6 decreased to that of before EPA. The change rate of α(1)-acid glycoprotein ( α(1)-AGP) increased in the group in which IL-6 was unchanged and did so significantly in the group in which it increased, but tended to increase in the group in which it decreased. Thus the change rate of sialic acids (SA) increased significantly in both the IL-6 unchanged and increased groups. It is suggested that EPA activated IL-6, which was related to the increase of α(1)-AGP as an activator of immunity. The change rate of sialic acid (SA) as an index of acute phase protiens was correlated significantly and positively with that of total cholesterol and HDL-cholesterol.

In order to assess the effect of passive smoking at home, 39 female junior college students and their mothers were surveyed concerning paternal smoking habits and asked to provide early morning urine samples in which the concentrations of cotinine (COT) and hydroxyproline (HOP) were measured. The concentration of urinary COT per gm creatinine (COT/Cr) of smoker was 1, 000 μg/g or more. There was no correlation between the number of cigarettes smoked per day by the father and the concentration of COT/Cr of either the mother or daughter. Their levels of COT/Cr remained 0-30μg/g irrespective of the father's smoking. The cases in which no COT was detected in either daughters or mothers were actually more frequent with heavier paternal smoking. There was also no relationship between the father's smoking and the concentration of HOP/Cr of the daughters and their mothers. One possible explanation of these findings may be that fathers who smoke at home do so outside of the room. Smoking by mothers was also found to not increase the concentration of COT/Cr of their daughters or rather low level of 5 μg/g. Thus, passive smoke at home did not show any effects on nicotine metabolite of daughters and mothers. The COT/Cr levels of daughters did increase significantly by 61 percent from 11.0 μg/g, as the result of a one hour exposure to heavy smoke in a meeting room.

Many risk factors have been proposed for systemic lupus erythematosus (SLE). However, there is little information about the relationship between lifestyles and SLE in Japan. Two case control studies were conducted in Kyushu, southern Japan, and in Hokkaido, northern Japan, to examine the relationship between lifestyles and development of SLE in females. The participants were 78 patients and 329 controls in Kyushu and 35 patients and 188 controls in Hokkaido. Smoking was associated with an increased risk of SLE after adjusting for age in both regions. However, in Hokkaido, this association between smoking and SLE did not reach statistical significance after adjusting for alcohol drinking. The present study suggests that smoking may increase the risk of SLE among Japanese females.

BACKGROUND: This study was conducted to describe the epidemiologic features of amyotrophic lateral sclerosis (ALS) in Japan by examining annual trends in mortality (1995-2001), and to discuss the background factors possibly responsible for the recent variations in the mortality rate.METHODS: Trends in both the age-adjusted and age-specific mortality rates of ALS were examined by using the data obtained from the vital statistics of Japan between 1995 and 2001.RESULTS: There were small increases in the number of ALS deaths (from 1249 to 1400 per year) and the crude mortality rates (from 1.00 to 1.10 per 100,000 population) between 1995 and 2001. The ageadjusted mortality rate of ALS (adjusted using the 1985 model population of Japan) has decreased (from 0.84 per 100,000 population in 1995 to 0.74 in 2001). Age-specific mortality rates have been increasing particularly in the population older than 70 years of age, with the peak in mortality in the 70- to 80- year old age group.CONCLUSIONS: ALS mortality rates increased proportionally more for elderly population during the study period. Further epidemiologic studies will be needed to clarify the possible background factors contributing to the increase in ALS mortality in the elderly.J Epidemiol 2005;15:20-23.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown etiology. Environmental factors, especially occupational agents, may be of great importance in the manifestation of IPF. We examined the relationship between occupational and environmental factors and IPF in Japan. A multicenter hospital-based case-control study was performed in 2001. Included were 102 cases aged 40 years or over who were within 2 years of having been diagnosed in accordance with the most recent criteria. Controls, aged 40 years or over, were 55 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with common colds. Data on occupational and environmental factors were obtained from a questionnaire. Multiple logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of IPF for single factors with adjustment for age, sex and region. Compared with controls, cases were more likely to have been managers, officials or production workers and less likely to have been protective service or materials handling workers. Clerical and related work was significantly related to a decreased risk of IPF after further adjustment for pack-years of smoking (OR = 0.42; 95% CI = 0.18-0.95). Exposure to metal dust was significantly associated with an increased risk of IPF (OR = 9.55; 95% CI = 1.68-181.12). From 20.0 to 39.9 pack-years of smoking was significantly associated with an increased risk of IPF (OR = 3.23; 95% CI = 1.01-10.84). Our results appear to confirm data from previous epidemiologic studies. Metal dust exposure may be a particularly important risk factor for IPF.

BACKGROUND: Although the average age of onset of ossification of the posterior longitudinal ligamen of the spine (OPLL) is at around 50 years, the onset of the symptoms is insidious and the progression is very slow. The etiology of OPLL has not been elucidated in detail. Previous studies have suggested that a high-salt diet and low consumption of animal protein, glucose intolerance and high body mass are risk factors for OPLL. However, there is little information about the relationship between OPLL and life styles in the prime of life (between 30 and 50 years). METHODS: To facilitate early prediction and prevention of OPLL, we analyzed life styles such as sleeping habit, physical exercise, smoking, alcohol drinking and hangover in subjects in the prime of life. Self-administered questionnaires were obtained from patients with OPLL and their sex- and age-matched controls. Sixty-nine patients diagnosed with OPLL within 3 years previously and 138 sex- and age-matched controls without backbone diseases, randomly selected from participants in a health checkup in a local town, were enrolled. RESULT: Moderate amount of sleep (6-8 hours vs. 5 hours or shorter and 9 hours or longer; odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.06, 0.54) and a regular sleeping habit (i.e., going to bed and getting up at regular time) (OR=0.44, 95% CI=0.22, 0.90) were associated with a decreased risk o OPLL even after adjusting for other factors. On the other hand, moderate physical exercise (once a week or more v.s. less than once a week: OR=0.97, 95% CI=0.42, 2.26), smoking (OR=1.41, 95% CI=0.67, 2.97), drinking (OR=1.08, 95% CI=0.53, 2.20) and hangover (OR=1.12, 95% CI=0.43, 2.94) in the prime of life showed no correlation with risk of OPLL. CONCLUSION: Good sleeping habits in the prime of life may decrease the risk of OPLL.

Aims: There has been little interest in the role of nutrition in prevention of idiopathic pulmonary fibrosis (IPF). We investigated the relationship between dietary intake of vegetables, fruit, cereals, antioxidants, and fiber and the risk of IPF in Japan. Methods: Included were 104 cases aged 40 years or over who were within 2 years of the diagnosis in accordance with the most recent criteria. Controls aged 40 years or over comprised 56 hospitalized patients diagnosed as having acute bacterial pneumonia and 4 outpatients with common cold. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age, sex, region, pack-years of smoking, employment status, occupational exposure, saturated fatty acid intake, and body mass index. Results: Consumption of fruit in the second and third quartiles was associated with a statistically significant reduced risk of IPF. Although not statistically significant, a beneficial association between soluble fiber intake and IPF was found. No statistically significant dose-response relationship was observed between intake of green and yellow vegetables, other vegetables, cereals, β-carotene, vitamins C and E, or insoluble fiber and the risk of IPF. Conclusion: Our findings suggest that fruit intake may confer protection against the development of IPF.

To assess the effect of eicosapentaenoic acid (EPA) intake on fibrinolysis and coagulation, 30 male subjects, approximately 19-23 y old, were examined for plasma fibrinolytic and coagulation activity by using a bicycle ergometer load (90 W, 20 min) before and after EPA intake of 1.125 g/d for 2 wk. Because of the EPA intake, the fibrinolytic activity was promoted, the plasmin-alpha 2 plasmininhibitor complex (PIC) level was decreased by 16.7%, and the thrombin-antithrombin III complex (TAT) level was increased by 75.4%; conversely, the D-dimer of the fibrin degradation peptide (D-dimer) level did not change from that before EPA intake. By the physical load, 1 h after ingesting the load, the PIC level was significantly decreased by 26.7%, the TAT level was significantly increased by 51.1%, and the D-dimer level was significantly decreased by 24% in comparison with levels before EPA intake. Thus, as determined by the load, a small amount of daily EPA intake clearly decreased fibrinolytic activity and increased coagulation activity. One hour after a physical load, the rate of change of the gamma-glutamyl transpeptidase (gamma-GTP) level correlated significantly and negatively to the rate of change in the PIC and TAT levels. Thus, EPA intake may affect liver and kidney function. EPA intake decreased systolic blood pressure by 5 mmHg and diastolic blood pressure by 10 mmHg.

To assess Vitamin K (VK) status by food questionnaire, healthy young males (32) and females (9) were given a food list of 50 VK rich foods (identified in the 4th edition standard tables of food composition in Japan). After checking the food names and approximate amount eaten for 7 days, early morning blood and urine samples were collected. Prothrombin and hepaplastin was tested and plasma protein induced by VK absence factor II (PIVKA-II), osteocalcin, and calcium, phosphorous and magnesium in plasma and urine were determined. Participants who have a habit of eating natto, a traditional Japanese food very rich in Vitamin K, VK were excluded, and lowest and highest VK consumers were compared (males; lowest 7 vs. highest 7, females; 3 vs. 3). Plasma PIVKA-II levels, and urinary calcium and magnesium excretion of the lowest was significantly higher, but urinary phosphorus was lower, than that of the highest in females. In the natto eaters, daily mean VK intakes and hepaplastin test results of natto eaters were significantly higher, but urinary calcium excretions were lower than that of non natto eaters in males. These results suggest that Daily VK intake estimated from a questionnaire, is well related to real VK status, and also that natto is a good dietary source of vitamin K.