Shigeo Tomura

Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren.

Abstract. The purpose of this study was to assess the influence of single nucleotide polymorphism 3 (SNP3) of the apolipoproteinxa0A-V (APOA5) gene on the serum triglyceride (TG) level in Japanese schoolchildren. To determine the frequency of the genotype, we analyzed 552 schoolchildren. The frequencies of the T/T, T/C and C/C genotypes of the APOA5 gene were 225 (40.8%), 263 (47.6%) and 64 (11.6%), respectively. The serum TG level was significantly different among the genotypic groups after adjustments for age, gender and obesity index (T/T 71.6±34.8xa0mg/dl, T/C 80.7±36.1xa0mg/dl, C/C 94.4±69.4xa0mg/dl, P<0.0001). The odds ratio (95% confidence interval) for hypertriglyceridemia of the C allele was 2.4 (1.0–6.2). Our data suggested that the T/C promoter region polymorphism of the APOA5 gene appears to be a genetic risk factor for hypertriglyceridemia in Japanese children.

Is cognitive impairment a risk factor for poor compliance among Japanese elderly in the community

Abstract.Objective: The association between cognitive impairment and compliance with prescribed medications was investigated among functionally independent Japanese elderly in the community. Subjects: The subjects of this study were 220 elderly persons aged 60 years and over, who lived in the community. All participants were taking a regimen of one or more prescribed drugs. We included elderly with mild to moderate cognitive impairment. Medication use was observed by pharmacist-conducted interviews during home visits. Compliance was estimated by the pill count method. The Mini-Mental State Examination (MMSE) was used to estimate cognitive function. Results: The mean age (SD) of the subjects was 75.7 (6.9) years. Of the subjects, 58 (26.4%) were cognitively impaired (MMSE≤23), and 76 (34.6%) exhibited poor compliance (rate of compliance<80%). Poor compliance was associated with the subjects who had a lower education level, had lower MMSE scores, had concern about taking drugs, who intentionally self-selected (intentional noncompliance) prescribed drugs, had a poor relationship with a physician, who did not have one dose package, and those who did not use a medical calendar. In multiple logistic regression analyses, intentional noncompliance (OR 19.65, 95%, CI 9.22–41.92; OR, odds ratio; CI, confidence interval), cognitive impairment (MMSE≤23; OR 2.94, 95%, CI 1.32–6.58), and a poor relationship with a physician (OR 6.24, 95%, CI 1.55–25.20) were independent predictors of poor compliance for elderly in the community. Conclusion: We found that cognitive impairment was one of the predictors for poor compliance among the elderly who are functionally independent in the community. Intentional noncompliance was the strongest predictor for poor compliance, which was influenced by the relationship between patient and physician. Physicians should establish good communication with their elderly patients and provide some support to compensate for cognitive impairment.

Pulmonary toxicity induced by intratracheal instillation of Asian yellow dust (Kosa) in mice

Asian yellow dust (Kosa) causes adverse respiratory health effects in humans. The objective of this study was to clarify the lung toxicity of Kosa. ICR mice (5 weeks of age) were administered intratracheally with Kosa samples-two samples from Maowusu desert and Shapotou desert, one sample consisted of Shapotou Kosa plus sulfate, and natural Asian dust (NAD) from the atmosphere of Beijing-at doses of 0.05, 0.10 or 0.20mg/mouse at four weekly intervals. The four Kosa samples tested had similar compositions of minerals and concentrations of elements. Instillation of dust particles caused bronchitis and alveolitis in treated mice. The magnitude of inflammation was much greater in NAD-treated mice than in the other particles tested. Increased neutrophils, lymphocytes or eosinophils in bronchoalveolar lavage fluids (BALF) of treated mice were dose dependent. The number of neutrophils in BALF at the 0.2mg level was parallel to the content of β-glucan in each particle. The numbers of lymphocytes and eosinophils in BALF at the 0.2mg level were parallel to the concentration of SO(4)(2-) in each particle. Pro-inflammatory mediators-such as interleukin (IL)-12, tumor necrosis factor-(TNF)-α, keratinocyte chemoattractant (KC), monocyte chemotactic protein (MCP)-l and macrophage inflammatory protein-(MIP)-lα in BALF-were greater in the treated mice. Specifically, NAD considerably increased pro-inflammatory mediators at a 0.2mg dose. The increased amounts of MlP-lα and TNF-α at 0.2mg dose corresponded to the amount of β-glucan in each particle. The amounts of MCP-l or IL-12 corresponded to the concentration of sulfate (SO(4)(2-)) at a 0.2mg dose. These results suggest that inflammatory lung injury was mediated by β-glucan or SO(4)(2-), which was adsorbed into the particles, via the expression of these pro-inflammatory mediators. The results also suggest that the variations in the magnitude of inflammation of the tested Kosa samples depend on the amounts of these toxic materials.

Compliance and medication knowledge among elderly Japanese home-care recipients

AbstractObjectives: To investigate the risk factors for noncompliance in elderly home-care recipients; and to evaluate to what extent regular home visits and drug counseling by a pharmacist contribute to compliance.nn Subjects: One hundred and sixty-three elderly home-care recipients aged 62 years and over took part in this study. All subjects were cognitively normal, and taking a regimen of one or more prescribed drugs. Medication use was observed by pharmacist-conducted interviews during home visits. Compliance was estimated by comparing prescribed regimens with medications actually being taken at home.nn Results: The mean age with (SD) of the subjects was 78.7 (8.3) years. Eighteen per cent were regularly counseled by a pharmacist about medication. Poor compliance with prescribed medications was associated with subjects aged 80 years and over, who were administering their own medication, consuming less than three meals a day, did not have one dose packages, and who were not receiving pharmacist counseling. In multiple logistic regression analyses, frequency of meals (OR 5.99; 95% CI 1.25–28.79), pharmacist counseling (OR 5.32; 95% CI 2.00–14.20), and age (OR 0.96; 95% CI 0.92–1.00) were independent predictors of good compliance for home-care recipients with physical disabilities. Compliance correlated inversely with knowledge of drug names, and drug purposes in the uncounseled group. Compliance, however, positively correlated with knowledge of drug purposes in the counseled group.nn Conclusion: In this study, compliance among elderly Japanese home-care recipients was found to be associated with receiving pharmacist counseling, frequency of meals, and age.

Effects of phenanthraquinone on allergic airway inflammation in mice

Diesel exhaust particles (DEP) enhance allergic airway inflammation in mice (Takano et al., Am J Respir Crit Care Med 1997; 156: 36–42). DEP consist of carbonaceous nuclei and a vast number of organic chemical compounds. However, it remains to be identified which component(s) from DEP are responsible for the enhancing effects. 9,10‐Phenanthraquinone (PQ) is a quinone compound involved in DEP.

Naphthoquinone enhances antigen-related airway inflammation in mice.

The current authors have previously demonstrated that diesel exhaust particles (DEP) enhance antigen-related airway inflammation in mice. Furthermore, a recent study has shown that organic chemicals in DEP, rather than their carbonaceous nuclei, are important contributors to the aggravating effects of airway inflammation. However, the components in DEP responsible for the enhancing effects on the model remain to be identified. The current authors investigated the effects of naphthoquinone (NQ), one of the extractable chemical compounds of DEP, on antigen-related airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin (Ig) production in mice. Pulmonary exposure to NQ dose-dependently aggravated antigen-related airway inflammation, as characterised by infiltration of eosinophils and lymphocytes around the airways and an increase in goblet cells in the bronchial epithelium. Combined exposure to NQ and antigen enhanced the local expression of interleukin (IL)-4, IL-5, eotaxin, macrophage chemoattractant protein-1 and keratinocyte chemoattractant, compared with exposure to antigen or NQ alone. Also, NQ exhibited adjuvant activity for the antigen-specific production of IgG1 and IgG2a. These results provide the first experimental evidence that naphthoquinone can enhance antigen-related airway inflammation in vivo, and that naphthoquinone can, to some extent, partly play a role in the pathogenesis of diesel exhaust particle toxicity on the condition.

Prevalence of Microalbuminuria and Relationship to the Risk of Cardiovascular Disease in the Japanese Population

The prevalence of microalbuminuria and its relationship to cardiovascular disease risk factors were examined in subjects participating in an annual physical and laboratory examination program. The urinary albumin concentration and the urinary albumin/creatinine ratio were determined in morning urine specimens. A turbidimetric immunoassay was used for the measurement of urinary albumin. Of the 731 subjects, 41 (5.6%) who were weakly positive or positive on a routine dipstick test for protein were excluded from the final analysis of data. Microalbuminuria was present in 14.5% of the men, in 12.4% of the women, and in 13.2% of the entire subject population when defined as a urinary albumin concentration of 30–299 μg/ml. The prevalence of microalbuminuria was significantly higher in subjects with a high normal blood pressure (15.0%) or hypertension (26.2%) as compared with normotensive subjects (6.5%). Subjects with impaired glucose tolerance (24.3%) or hyperglycemic subjects (50.0%) had a significantly higher prevalence of microalbuminuria than normoglycemic subjects (11.3%). The prevalence of microalbuminuria was significantly higher in subjects with left ventricular hypertrophy (47.1%) as compared with those with normal electrocardiograms (11.3%). A good correlation was observed between urinary albumin concentration and albumin/creatinine ratio, and both showed a significant positive correlation with age, systolic and diastolic blood pressures, and fasting plasma glucose, total serum protein, albumin, and triglyceride levels, but not with angiotensin-converting enzyme activity. Multiple regression analysis demonstrated that both the urinary albumin concentration and the albumin/creatinine ratio show a significant positive correlation with systolic blood pressure and fasting plasma glucose. The prevalence of microalbuminuria was about 13% in this Japanese cohort, and the systolic blood pressure and the fasting plasma glucose level were demonstrated as independent risk indicators for both urinary microalbumin level and urinary microalbumin/creatinine ratio.

Experimental IgA Nephropathy Induced by a Low-Dose Environmental Mycotoxin, Nivalenol

Based on the hypothesis that IgA nephropathy (IgAN) is triggered by some exogenous antigen(s) which induces dysregulation of the mucosal immune system, we developed an experimental model of orally induced IgAN by an environmental mycotoxin, nivalenol (NIV), which often contaminates agricultural products in Southeast Asia and Japan. In the present study, low doses of oral NIV reproducibly induced significant IgA deposits in the glomerular mesangium and elevated serum IgA levels in mice irrespective of the strain; the degree of immunopathological changes analogous to human IgAN was associated with the dose and duration of NIV treatment. Furthermore, a competitive enzyme-linked immunosorbent assay with an NIV analogue-protein conjugate disclosed that the IgA antibody in the sera from the NIV model mice had a higher affinity to the mycotoxin. Conclusively, these findings suggest that NIV induces some pathological changes in mice which resemble those in human IgAN, and that this mycotoxin is associated with pathogenesis in some types of glomerulonephritis.

Effect of physical activity during teenage years, based on type of sport and duration of exercise, on bone mineral density of young, premenopausal Japanese women.

In this cross-sectional study, 91 healthy premenopausal women aged 20–39 years were investigated to determine the effect of physical activities during their teen-age years on their current bone mineral densities (BMD). We measured whole-body BMD (WBMD), lumbar BMD (LBMD), and radial BMD (RBMD) with dual energy X-ray absorptiometry (DXA). Using a questionnaire, we asked the women about their physical activities during junior and senior high school and at present. We also asked about their current nutritional status and past and current milk intake. After adjusting for age, body mass index (BMI), current total calorie and calcium (Ca) intake, and milk intake when they were teenagers and at present, we determined that subjects who exercised during extracurricular activities at each of the three periods (during junior and senior high school and at present) had significantly higher WBMD and LBMD (P<0.01, respectively) than did those who did not exercise at those times. Subjects who played high-impact sports at each period had significantly higher WBMD and LBMD than did subjects who played low-impact sports (P<0.05, respectively). Subjects who had exercised regularly from their teenage years to the present had significantly higher BMD at all sites than BMD in other subjects after adjusting for the potential confounders described above (P<0.05, respectively). Our data suggest that continuous exercise beginning in junior high school, especially high-impact sports, may be associated with greater current bone mass. It is important to incorporate adequate exercise beginning in the teenage years to lower one’s future risk for osteoporosis.

Effects of hormone replacement therapy and methylenetetrahydrofolate reductase polymorphism on plasma folate and homocysteine levels in postmenopausal Japanese women

OBJECTIVEnTo evaluate the relationships among the methylenetetrahydrofolate reductase (MTHFR) polymorphism, plasma folate, total homocysteine (Hcy) levels, lipids, and the reduction of Hcy levels resulting from hormone replacement therapy (HRT).nnnDESIGNnClinical study.nnnSETTINGnOutpatient department of obstetrics and gynecology in a general hospital.nnnPATIENT(S)nTwo hundred seventeen postmenopausal Japanese women.nnnINTERVENTION(S)nOf the 217 women, 172 patients were under continuous treatment with oral conjugated equine estrogen and medroxyprogesteron acetate.nnnMAIN OUTCOME MEASURE(S)nFasting Hcy, folate, methionine, lipids, and apolipoproteins were measured before and after 3 months of HRT.nnnRESULT(S)nThe plasma Hcy concentration was significantly higher in the low folate than in the high-folate group only in patients with the homozygous (T/T) mutant. Plasma Hcy concentrations were significantly correlated with age (R = 0.64, P=.02) or years since menopause (R = 0.73, P=.02) only in the low-folate group with T/T. The plasma Hcy concentration decreased significantly in all genotypes after 3 months of HRT, but the levels of serum folate and methionine remained unchanged.nnnCONCLUSION(S)nThe MTHFR polymorphism was associated with a higher Hcy concentration, and this association was related to the serum folate level. Hormone replacement therapy reduced the plasma Hcy concentration independently of the MTHFR polymorphism.