Hisako Yanagi

Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene.

The molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined. Her parents were first cousins. Her plasma density fraction from 1.063 to 1.21 g/ml contained no apoA-I on SDS/PAGE and no measurable high density lipoprotein cholesterol. Southern blot hybridization showed no gross abnormality to be present in the patients apoA-I gene and homozygosity for a haplotype of restriction fragment length polymorphisms in the apoA-I gene region. Sequencing after amplification by PCR revealed a codon 84 nonsense mutation (CAG----TAG, Gln----stop) of exon 4 and a codon 67 missense mutation (GCC----ACC, Ala----Thr) of exon 3 in the patients apoA-I gene. The data from dot-blot hybridization with allele-specific oligonucleotide probes indicated that she was homozygous for the apoA-I gene with regard to the two mutations. The codon 37 missense mutation was also detected in the apoA-I gene of 6 out of 60 controls, who all had normal levels of apoA-I and high density lipoprotein cholesterol, suggesting that the missense mutation is polymorphic and not associated with apoA-I deficiency. These findings indicate that homozygosity for the apoA-I gene with codon 84 nonsense mutation causes the deficiency of apoA-I and of high density lipoprotein cholesterol in the patient.

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.

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. 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. 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. 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.

Effect of age on carotid arterial intima-media thickness in childhood.

To investigate relationships between carotid arterial intima-media thickness (IMT) and age in childhood, we performed high-resolution carotid arterial ultrasonography in 60 healthy children (27 boys, 33 girls; age range, 5–14 years) determined by screening to have no dyslipidemia or hypertension. No plaque formation was found, and irregularity of IMT (root mean square roughness of IMT) did not correlate with age. Mean IMT increased in a linear manner with age [IMT in millimeters = (0.009 × age in years) + 0.35] (r = 0.39, P = 0.002). This correlation remained significant after adjustment for gender, parental smoking, systolic and diastolic blood pressure, body mass index, and serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. None of these known cardiovascular disease risk factors in adults had a significant relationship with age-adjusted IMT in children. While circumferential wall stress and diastolic blood pressure were not correlated with age, mean IMT and lumen diameter showed significant positive relationships with circulating blood volume, which was calculated as the function of height and weight. These data suggested that age-dependent physiologic thickening of arterial walls begins in childhood.

Relationship between serum HDL-C levels and common genetic variants of the endothelial lipase gene in Japanese school-aged children

Endothelial lipase (EL) is a new member of the triglyceride lipase family, the genes of which play a central role in dietary fat absorption, energy homeostasis, and plasma lipoprotein metabolism. One physiologic role of EL is thought to be hydrolysis of high-density lipoprotein (HDL) phospholipid, although the precise function of endothelial lipase has yet to be fully clarified. Furthermore, genetic variation in EL has been suggested to influence serum HDL-C levels. In the present study, we detected two common single nucleotide polymorphisms in the EL gene associated with serum HDL cholesterol levels in healthy school-aged children. Our data support the hypothesis that variations in the EL gene are one of the genetic determinants of serum HDL-C levels.

Locomotion Improvement Using a Hybrid Assistive Limb in Recovery Phase Stroke Patients: A Randomized Controlled Pilot Study

OBJECTIVE To compare the efficacy of gait training using a single-leg version of the Hybrid Assistive Limb (HAL) on the paretic side with conventional gait training in individuals with subacute stroke. DESIGN Randomized open controlled pilot trial. SETTING Hospitalized care. PARTICIPANTS Convenience sample of 44 patients who met the criteria; 12 patients refused. After randomization (N=32), 10 patients withdrew and a total of 22 poststroke participants (HAL group: n=11; conventional group: n=11) completed the randomized controlled trial. INTERVENTIONS All participants received twelve 20-minute sessions in 4 weeks of either HAL (wearing the single-leg version of the HAL on their paretic side) or conventional (performed by skilled and experienced physical therapists) gait training. MAIN OUTCOME MEASURES Outcome measures were evaluated prior to training and after 12 sessions. Functional Ambulation Category (FAC) was the primary outcome measure, whereas secondary outcome measures included maximum walking speed, timed Up and Go test, 6-minute walk distance, Short Physical Performance Battery, Fugl-Meyer Assessment of Lower Extremity, and isometric muscle strength (hip flexion and extension, knee flexion and extension). RESULTS No participants withdrew because of adverse effects. Participants who received gait training with the HAL showed significantly more improvement in the FAC than those who received conventional gait training (95% confidence interval, .02-.88; P=.04). Secondary measures did not differ between the 2 groups. CONCLUSIONS The results obtained in this randomized controlled trial suggest that a gait training program with the HAL could improve independent walking more efficiently than conventional gait training.

Data on the CGG repeat at the fragile X site in the non-retarded Japanese population and family suggest the presence of a subgroup of normal alleles predisposing to mutate

The fragile X mutation is the result of amplification in the repeat number of p(CGG)n in FMR-1; alleles with more than 52 repeats have been shown to be so unstable as to mutate in the repeat number in almost every transmission. To improve our understanding of mutations in normal alleles of FMR-1, the following studies were carried out in the Japanese population: a study on length variation in the repeat to determine the allele distribution of the repeat length in a non-retarded population, family studies to observe new mutations in normal allele, and haplotype analyses with microsatellite markers flanking the repeat to confirm estimated mutation rates and founder chromosomes in the fragile X syndrome. Analysis of the p(CGG)n in 370 unrelated males detected 24 distinct alleles with repeats of 18–44. A comparison with previously reported data suggests the presence of racial/ethnic differences in the allele distribution. No premutation allele was found in 824 unrelated X chromosomes examined by the polymerase chain reaction and Southern blot analysis. Family studies detected one new mutation in a total of 303 meioses. However, the mutation rate was not in accordance with the expected or observed heterozygosities in the population or with linkage disequilibrium observed between the repeat numbers and the haplotypes of the markers flanking the CGG. The haplotype in the chromosome in which the new mutation was found was the same as that frequently found in the Japanese fragile X chromosomes, and the variance in the CGG repeat number was wider in chromosomes with the haplotypes frequently found in the fragile X chromosome than in those with the other haplotypes. These observations suggest that a subgroup is present in normal alleles and that this subgroup is more liable to mutate than others.

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.

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.

Three novel partial deletions of the low-density lipoprotein (LDL) receptor gene in familial hypercholesterolemia

SummaryThe low-density lipoprotein (LDL) receptor genes from 18 unrelated Japanese heterozygotes and 1 homozygote with classical familial hypercholesterolemia were analyzed by Southern blot hybridization using fragments of the human LDL receptor cDNA as probes. Four different deletion mutations were detected among 20 mutant LDL receptor genes (20%); they were characterized by restriction mapping. None of these mutations has previously been reported in Caucasian patients with FH: three of the mutations were novel and one was similar to the detetion mutation of FH-Tonami described previously in Japanese patients. In three of the four deletion mutations, the rearrangements were related to intron 15 of the LDL receptor gene, in which many Alu sequences exist. The data suggest that a wide range of molecular heterogeneity exists even in major rearrangements resulting in deletions in the LDL receptor gene. The data also support the hypothesis that there are preferential sites within the LDL receptor gene for major rearrangements resulting in deletions. The possibility that a higher frequency of deletion mutations occurs in classical FH than previously suspected is discussed.