Masao Satoh

Vaccination of domestic pig with recombinant paramyosin against Schistosoma japonicum in China.

Paramyosin (PM), a myosin-like protein is a major antigen on Schistosoma japonicum (Sj). We reported that passive transfer of a monoclonal IgE SjE18varepsilon.1 which recognizes PM of Sj (SJPM), partially protected mice from challenge infection. In the present study, we developed an experimental model system of schistosomiasis japonica with domestic pigs in China and used it for the evaluation of vaccination with recombinant SJPM (rSJPM). Sixteen-week-old pigs were successfully infected by dermal penetration of 120 cercariae of a domestic strain of Sj (50-60% worm recovery 11 weeks after challenge). The pigs vaccinated with 400 UV attenuated cercariae showed a reduction of worm recovery (53%, p<0.001). The experimental groups were immunized intradermally with rSJPM and alum or TiterMax and were partially protected against the challenge infection (32-35% reduction).

Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure in the Japanese population.

It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism, also called NADH dehydrogenase subunit 2-237 methionine/leucine (ND2-237 Met/Leu) polymorphism, may be associated with longevity in Japanese individuals, and that the mt5178A genotype may have an antiatherogenic influence. To determine whether mt5178 A/C polymorphism influences blood pressure, we genotyped 412 healthy Japanese individuals and performed a cross-sectional study investigating the relationship between genotype and blood pressure. In women with mt5178A, the mean diastolic blood pressure was higher than in those with mt5178C by 3.2 mmHg (P=0.040). In men, no statistically significant difference in systolic or diastolic blood pressure was observed between mt5178 A/C genotypes. However, a significant correlation between mt5178 A/C genotypes and the effects of habitual drinking on blood pressure was found. After adjustment for several factors, in men carrying mt5178C, both systolic and diastolic blood pressure were significantly higher in daily drinkers than in occasional (P=0.002 and 0.002, respectively) as well as nondrinkers (P<0.001 and 0.001, respectively), whereas in men carrying mt5178A, no significant differences in blood pressure were detected, irrespective of alcohol consumption. These results suggest that mt5178 A/C (=ND2-237 Met/Leu) polymorphism may influence both diastolic blood pressure in Japanese women and the blood-pressure-increasing effect of drinking in Japanese men.

Longevity-associated mitochondrial DNA 5178 A/C polymorphism modulates effects of daily drinking and cigarette consumption on serum triglyceride levels in middle-aged Japanese men

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is one of the longevity-associated mitochondrial DNA polymorphisms. The frequency of the mt5178A genotype is significantly higher in Japanese centenarians than in the general population. We previously reported that serum high-density lipoprotein cholesterol levels were significantly higher in men with mt5178A than in those with mt5178C. However, this significant difference disappeared after adjusting for drinking frequency. To investigate the interaction between mt5178 A/C polymorphism and habitual drinking on serum lipid levels, we performed an association study in 321 healthy middle-aged Japanese men. Interaction between mt5178 A/C polymorphism and daily drinking on serum triglyceride (TG) levels was observed (P=0.019). Moreover, interaction between mt5178 A/C polymorphism and cigarette consumption on serum TG levels was also observed (P=0.022). Multiple regression analysis showed that, in men with mt5178A, daily drinking decreased TG levels (P=0.025), and cigarette consumption increased TG levels (P<0.001), while in men with mt5178C, the effects of daily drinking and cigarette consumption on TG levels were unclear. No interaction was observed on other lipid levels. Longevity-associated mitochondrial DNA 5178 A/C polymorphism thus influences the effects of daily drinking and cigarette consumption on TG levels in middle-aged Japanese men.

NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Modifies the Effects of Alcohol Consumption on Risk for Hypertension in Middle-Aged Japanese Men

NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in the Japanese population, and the ND2-237Met genotype may exert antiatherogenic effects. To investigate whether ND2-237 Leu/Met polymorphism is associated with risk of hypertension, we conducted a cross-sectional study of 398 Japanese male subjects. The frequency of hypertension was significantly higher in ND2-237Leu genotypic men than in ND2-237Met genotypic men. On analysis of covariance, the interaction between ND2-237 Leu/Met polymorphism and habitual drinking was significantly associated with both systolic blood pressure and diastolic blood pressure. Multiple logistic regression analysis revealed that the ND2-237Met genotype, particularly in younger subjects (age <60 years), had a lower odds ratio for hypertension than the ND2-237Leu genotype. Moreover, the association of ND2-237 Leu/Met polymorphism with hypertension may depend on the frequency of alcohol consumption. The odds ratio for hypertension was significantly higher in daily drinkers with ND2-237Leu when compared with non- or ex-drinkers with ND2-237Leu. However, the association between the ND2-237Met genotype and hypertension may not depend on the frequency of alcohol consumption. The present results suggest that ND2-237 Leu/Met polymorphism is associated with hypertension and that modification of hypertension risk is dependent on alcohol consumption in middle-aged Japanese men.

Longevity-associated mitochondrial DNA 5178 A/C polymorphism is associated with intraocular pressure in Japanese men.

Background: Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism has been reported to be associated with longevity in Japanese individuals, with experimental findings concluding that mt5178 A is an anti‐atherogenic genotype. The aim of this study was to determine whether mt5178 A/C polymorphism influences intraocular pressure (IOP), and its relationship with the development of arteriosclerosis.

Association of the longevity-associated mitochondrial DNA 5178 A/C polymorphism with serum protein fraction levels in healthy Japanese women

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism was reported to be associated with longevity and susceptibility to adult-onset diseases in Japanese. To examine whether mt5178 A/C genotypes are associated with serum protein fraction profiles, we genotyped 461 healthy Japanese individuals, and studied the relationship of mt5178 A/C genotypes to both proportion and levels of serum protein fraction. The mt5178 A/C was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The alpha-1, alpha-2, and beta globulin proportions in females carrying mt5178A were significantly higher than those in females carrying mt5178C (P=0.002, 0.006, and 0.008, respectively). Moreover, the alpha-1, alpha-2, and beta globulin levels in females carrying mt5178A were significantly higher than those in females carrying mt5178C (P=0.001, 0.002, 0.018, respectively). This difference in globulin fraction level between the two genotypes was more evident in premenopausal females than in postmenopausal females. However, no such difference was found in males. These results provide the first evidence that the mt5178 A/C polymorphism may influence the serum protein fraction levels of the healthy Japanese women.

Longevity-associated mitochondrial DNA 5178 A/C polymorphism influences effects of cigarette smoking on serum protein fraction levels in Japanese men.

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is reportedly associated with longevity and susceptibility to age-related diseases in Japanese individuals. We previously reported an association between mt5178 A/C polymorphism and serum protein fraction levels in healthy Japanese women. An association between habitual smoking and serum protein fraction levels has also been reported previously. The aim of this study was to examine whether mt5178 A/C polymorphism influenced the effects of habitual smoking on serum protein fraction levels in 321 healthy Japanese men. In mt5178C genotype men, alpha-1 and alpha-2 globulin levels were higher in smokers than in nonsmokers (P<0.001, and P=0.002, respectively). The influence of smoking on these globulin levels depended on cigarette consumption. However, in mt5178A genotype men, no significant difference was observed in alpha-1 or alpha-2 globulin levels between smokers and nonsmokers. These results suggest that longevity-associated mt5178 A/C polymorphism may influence the effects of cigarette smoking on serum protein fraction levels in healthy Japanese men.

Longevity-associated NADH dehydrogenase subunit-2 237 Leu/Met polymorphism influences the effects of alcohol consumption on serum uric acid levels in nonobese Japanese men

AbstractNADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is reportedly associated with longevity in the Japanese population. The ND2-237Met genotype may confer resistance to cardiovascular and cerebrovascular atherogenic diseases. Hyperuricemia is one of the risk factors for cardiovascular disease. To investigate whether ND2-237 Leu/Met polymorphism is associated with serum uric acid (SUA) levels, we conducted a cross-sectional study in 321 healthy Japanese male subjects. In nonobese (body mass index, BMI<25) male subjects, interaction between ND2-237 Leu/Met genotypes and drinking frequency on SUA levels was observed (P=0.031). The SUA levels were significantly higher in daily drinkers with ND2-237Leu than in non-daily drinkers with ND2-237Leu (P=0.018). In nonobese men, after adjustment for covariates, daily drinkers with ND2-237Leu had a significantly higher odds ratio (OR) for hyperuricemia (SUA≥6.5 mg/dl: vs. daily drinkers with ND2-237Met, OR=3.26, 95% confidence interval (CI) 1.14-9.29; vs. non-daily drinkers with ND2-237Leu, OR=3.22, 95% CI 1.39-7.45; SUA≥7.0 mg/dl: vs. non-daily drinkers with ND2-237Met, OR=3.53, 95% CI 1.00-12.4). However, in obese (BMI≥25) men, no significant interaction between ND2-237 Leu/Met polymorphism and habitual drinking on SUA levels or on the risk for hyperuricemia was observed. These results suggest that ND2-237 Leu/Met polymorphism modulates the effects of daily alcohol consumption on SUA levels in nonobese Japanese men.

Longevity-associated mitochondrial DNA 5178 C/A polymorphism and its interaction with cigarette consumption are associated with pulmonary function in middle-aged Japanese men

AbstractPulmonary function is a crucial factor associated with longevity. Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reported to be associated with longevity in the Japanese population. We have previously reported that Mt5178 C/A polymorphism is widely associated with physiological and biochemical status. The objective of this study was to investigate whether Mt5178 C/A polymorphism is associated with pulmonary function. The subjects were 463 Japanese men (mean age ± SD 54.0 ± 7.6 years). Genotyping of Mt5178 C/A was performed by polymerase chain reaction-restriction fragment length polymorphism. A cross-sectional study of the relationship between genotype and spirometric data, namely forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), was conducted. Among younger subjects (age <55 years), FVC and FEV1 were significantly higher for men with Mt5178A than for those with Mt5178C. Interaction between Mt5178 C/A polymorphism and smoking habits in FEV1/FVC ratio was observed. Cigarette consumption (pack-years of smoking) was significantly and negatively associated with FEV1/FVC ratio for men with Mt5178C. Among older subjects (age ≥55 years), FEV1/FVC ratio was significantly lower for current smokers with Mt5178C than for never smokers with Mt5178C or for never smokers with Mt5178A. Mt5178 C/A polymorphism and its interaction with cigarette consumption may be associated with pulmonary function in Japanese men.

Longevity-associated NADH dehydrogenase subunit-2 polymorphism and serum electrolyte levels in middle-aged obese Japanese men

Mitochondrial DNA 5178 cytosine/adenine polymorphism, which is also called NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with Japanese longevity. This polymorphism is widely associated with blood pressure, serum lipid levels, hematological parameters, intraocular pressure, and serum protein fraction levels. However, there have been no reports on the association between ND2-237 Leu/Met polymorphism and serum electrolyte levels. To investigate this relationship, we performed an association study in 321 healthy middle-aged Japanese men. Crude data showed that serum sodium levels and serum chloride levels were significantly lower in men with ND2-237 Met than in those with ND2-237 Leu (P = 0.021 and 0.003, respectively). Cigarette consumption and body mass index were significantly and positively associated with serum chloride levels (P = 0.002 and 0.008, respectively) and hemoglobin levels were significantly and negatively associated with them (P = 0.007) in ND2-237 Leu genotypic men. In men with ND2-237 Met, only hemoglobin levels were significantly and negatively associated with serum chloride levels (P = 0.025). After adjusting for covariates, only in male obese (body mass index> or =25) subjects, serum sodium and chloride levels remained significantly lower, and serum calcium levels appeared to be significantly higher in ND2-237 Met than in ND2-237 Leu (P = 0.013, <0.001, and 0.046, respectively). Longevity-associated NADH dehydrogenase subunit-2 polymorphism may influence serum electrolyte levels in middle-aged obese Japanese men.