Zentaro Yamagata

Prevalence of Dementia and Distribution of ApoE Alleles in Japanese Centenarians: An Almost-Complete Survey in Yamanashi Prefecture, Japan

OBJECTIVE: To determine the prevalence and types of dementia in centenarians and to examine whether the ApoE 4 allele has significant impact on the development of Alzheimers disease (AD) in the population.

Apolipoprotein E allele in centenarians.

Sobel et al., 1 reporting the prevalence of apolipoprotein E (apoE) genotypes among Finnish centenarians, noted that the presence of the e4 allele does not necessarily lead to Alzheimers disease (AD) in this population and suggested that the relationship between the apoE e4 allele and AD may be age-dependent.nnRecently, we also carried out an almost complete survey of centenarians living in Yamanashi prefecture, a district of Japan with a population of 0.87 million, and determined the prevalence of apoE …

ApoE epsilon 4 allele and cognitive decline in patients with Alzheimer's disease

Many clinical and basic studies have confirmed an association between the apolipoprotein E (apoE) epsilon 4 allele and the development of Alzheimers disease (AD). Corder et al. [1] reported that survival from onset was unrelated to epsilon 4 gene dose. In this issue, Kurz et al. [2] report that no association of the apoE epsilon 4 allele with cognitive decline was found in AD subjects. We examined the relationship between apoE alleles and the rate of cognitive decline in a longitudinal study of up to 3 years.nnBetween February and October 1992, 105 subjects with probable AD diagnosed on the basis of NINCDS-ADRDA [3] criteria entered the study. All the subjects underwent a …

Distribution of apolipoprotein E gene polymorphisms in Japanese patients with Alzheimer's disease and in Japanese centenarians

We have demonstrated an association between apolipoprotein E (apoE) gene polymorphisms and Alzheimers disease (AD) in 163 Japanese patients by means of PCR. We found a significant increase in risk of nonfamilial AD for apoE allele epsilon4 in these individuals; this trend decreases with the increase in onset age. In centenarians, the distribution of apoE gene alleles is similar to that in the general population. The protective effect of allele epsilon2 against the development of AD is not statistically significant in our analysis. This indicates that apoE polymorphism is associated with AD regardless of race and that the age of onset is related to the apoE gene in the development of AD.

The effect of aging on cell-cycle kinetics and X-ray-induced chromosome aberrations in cultured lymphocytes from patients with Down syndrome

To evaluate the effects of aging on cytogenetic characteristics of lymphocytes from Down syndrome (DS), cell-cycle kinetics after PHA stimulation and chromosome-type aberration frequencies after X-ray exposure were investigated in vitro in the lymphocytes derived from 4 (or 3 for X-ray treatment) age groups of DS patients and age-matched controls. The results clearly showed higher mitotic and proliferation index levels in younger groups compared to older groups at the various culture intervals, whether the lymphocytes were from the DS patients or controls. The age-related changes of the proliferation index were mainly attributed to a delayed response to PHA as age increased. The changes of PHA responses seemed to be particularly marked during adolescence. Nonetheless, no significant differences were observed between the DS patients and age-matched controls for each age group. In all age groups, frequencies of both chromosome-type exchanges and deletions were elevated in the DS patients by about 1.3 times in comparison with the controls. The magnitude of radiosensitivity, however, seemed to decrease slightly in the 40-49-year group. To our knowledge, the present study is the first report in the literature to deal with the effect of aging on the greater radiosensitivity of DS lymphocytes.

Mitomycin-C-induced sister-chromatid exchanges and cell-cycle kinetics in lymphocytes from patients with Klinefelter syndrome

The chromosomal sensitivity to mitomycin-C (MMC) and cell-cycle kinetics in cells from patients with Klinefelter syndrome, a sex chromosomal disorder giving a high risk of malignant tumor, were studied by techniques of sister-chromatid exchanges (SCEs). The frequencies of MMC-induced SCEs increased in proportion to the increase in MMC concentration in both patient and normal control cells. At low levels of MMC there were no significant differences in SCE frequencies between the patient and normal control cells, but at MMC concentrations of 3 X 10(-8) M (p less than 0.05) and 1 X 10(-7) M (p less than 0.01), significant increases in the frequency of MMC-induced SCEs were observed in cells from patients compared to cells from normal controls. Although the analysis of cell-cycle kinetics both after various culture times and after treatment with MMC revealed that there were no significant differences between the patient and normal control cells, patients with Klinefelter syndrome showed a tendency to cell-cycle delays after treatment with MMC in comparison with normal controls.

Elevated chromosome aberration frequency after X-ray exposure of cultured fibroblasts derived from patients with porokeratosis.

Porokeratosis (PK) is a rare genetic skin disorder inherited as an autosomal dominant trait and regarded as a disease predisposing to cancer. To evaluate chromosomal radiosensitivity of PK cells, we examined chromosome aberration frequency after X-irradiation of cultured skin fibroblasts derived from PK patients and controls. Without X-ray exposure, frequencies of chromosome-type aberrations (exchanges or deletions) were not different between the patients and controls. Following X-ray irradiation, frequencies of deletions in the patient group were significantly increased, whereas those of exchanges were not elevated. No differences in chromatid-type aberration frequency were found between the patients and controls with or without exposure to X-ray. The observed radiosensitivity, though not as high as in ataxia telangiectasia (AT) cells, agrees well with the previously reported higher radiosensitivity of PK fibroblasts in survival analysis.

Structural quantification of bone from radiographs using power spectral analysis

Bone mineral density (BMD) and bone structure are very important indices for prevention of fracture. However, it is very difficult to quantify bone structure, and only a few indices for structural quantification of bone have been reported. The purpose of this research was to investigate a new index for bone structure. The subjects were 52 women aged from 20 to 85 years. Directivity index (DI) is a new index of bone structure calculated by directivity of power spectrum from radiographs of metacarpal bone using fast Fourier transform (FFT). DI was obtained by subtracting the integral power value at 0 and 90 degree directions on the x-y plane of the two-dimensional power spectrum of bone from the integral power value at a direction of 45 degrees. A significant relationship between BMD and DI was indicated by correlation coefficient. However, no significant relationship between BMD and the first moment of the Fourier power spectrum or the fractal dimension was found. There is a possibility that DI estimates a slight deformation of bone structure. In the future, we will apply DI to the prevention of fractures and osteoarthritis.