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Biomedical subjects

K Urakami

Publications and source records attributed to K Urakami.

86 records · Page 5Linked to original sources
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Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease.

Apolipoprotein E sigma4 allele (ApoE sigma4) is associated with Alzheimer's disease (AD) in familial and sporadic cases, but the associations of ApoE sigma4 allele and vascular dementia (VD) and/or ischemic cerebrovascular disease (ICVD) are still controversial. To clarify the associations of ApoE polymorphism with AD, VD and ICVD in Japanese, we examined ApoE polymorphism in samples of 255 patients with AD, 87 patients with VD, and 123 patients with ICVD, as compared with 117 age-matched healthy control subjects (CTL). The frequency of the ApoE sigma4 allele was significantly higher in the VD group (0.21), the ICVD group (0.15) as well as in the AD group (0. 26) than in the CTL subjects (0.08). These findings suggest that the genotype of ApoE sigma4 is associated with not only AD but also VD and ICVD, and that ApoE sigma4 plays an important role in the development of dementia and ICVD.

Aged↗
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Epidemiologic and genetic studies of dementia of the alzheimer type in japan.

We carried out two separate epidemiological studies on long-term changes, 10 years apart, on the prevalence rate of dementia in the elderly by the same method for the same area in Japan. We also performed a genetic study of patients with dementia of the Alzheimer type (DAT) based on the epidemiological studies. The number of patients with dementia was much larger in 1990 than in 1980. Especially, the number of mildly demented patients was significantly larger in 1990 than in 1980. The 35 patients with DAT did not show any mutations of amyloid-beta protein precursor, presenilin 1 and presenilin 2 genes. The frequency of apolipoprotein E (apo E) sigma4 allele in DAT was significantly higher than that in control subjects (p < 0.005). This study suggests that the frequency of DAT may increase by aging of the population in the future and we confirm the close association between apoE sigma4 allele and DAT in a community-based study in Japan.

Adolescent↗
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No association between apolipoprotein A-IV codon 360 mutation and late-onset Alzheimer's disease in the Japanese population.

Human apolipoprotein A-IV (apoA-IV) is genetically polymorphic, the apoA-IV polymorphism being controlled by two alleles, apoA-IV1 and apoA-IV2. The association between the apoA-IV2 allele and late-onset Alzheimer's disease (LOAD) has been reported in Caucasian populations. We investigated the codon 360 mutation of the apoA-IV gene allele frequency in 173 LOAD and in 158 age-matched control subjects of the Japanese population, and we found that the allele frequency of apoA-IV2 in the Japanese population was very rare and was extremely lower than in Caucasian populations. We conclude that there was no association between apoA-IV genotype and LOAD in the Japanese population. Copyrightz1999S.KargerAG,Basel

Age of Onset↗
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Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia.

The association between the estrogen receptor (ER-alpha) gene and dementia was examined in 223 patients with Alzheimer's disease (AD), 66 with vascular dementia (VD), 17 with alcohol-associated dementia (ALD) and 134 healthy elderly control subjects. The PvuII and XbaI restriction fragment length polymorphisms of the ER-alpha gene were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of restriction sites and small letters the presence of restriction sites. We found that the frequency of the ER-alpha gene P allele and X allele in the late-onset AD (LOAD) group (P allele was 0.51, X allele was 0.30) was significantly higher than that in controls (P 0.38, p < 0.01; X 0.20, p < 0.01), and that the frequency of the ER-alpha gene P allele and PP genotype was significantly different between apolipoprotein E epsilon4 carriers and noncarriers in LOAD. These findings suggest that the genotype of the ER-alpha gene may be specific in LOAD, and that the ER-alpha gene was an additional risk for LOAD.

Aged↗
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Lipoprotein(a) phenotypes in patients with vascular dementia.

We tried to examine if there is a particular distribution pattern of lipoprotein(a) [Lp(a)] phenotypes specific for patients with vascular dementia (VD). Fourteen cases of VD (9 males and 5 females), 18 cases of dementia of the Alzheimer type (DAT)(7 males and 11 females), 29 cases of cerebrovascular disease (CVD) in the chronic phase (18 males and 11 females) and 47 healthy individuals as controls (25 males and 22 females) were examined for serum Lp(a). Serum concentrations and phenotypes of Lp(a) were assessed by ELISA and a test kit for the Lp(a) phenotype, respectively. Serum concentrations of Lp(a) were significantly higher in patients with VD (p < 0.05) as well as patients with CVD (p < 0.01) compared with those in healthy individuals. Serum concentrations of Lp(a) did not significantly differ between patients with DAT and healthy individuals. The incidences of Lp(a) phenotypes containing relatively low-molecular-weight apolipoprotein(a) isoforms were significantly higher in patients with CVD in the chronic phase (p < 0.05) or those with VD (p < 0.01) compared with those in healthy individuals. Distribution patterns of Lp(a) phenotypes did not differ between patients with DAT and healthy individuals. Thus, high serum levels of Lp(a) could be considered a clinical hallmark to distinguish VD from DAT. Abnormally high serum levels of Lp(a) in patients with CVD and VD seemed to be due to specific increases in low-molecular-weight apolipoprotein(a) isoforms in Lp(a).

Aged↗
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The expression of presenilin 1 mRNA in skin fibroblasts and brains from sporadic Alzheimer's disease.

We examined the expression of presenilin 1 (PS-1) mRNA in cultured skin fibroblasts taken from living patients with Alzheimer's disease (AD) and human brains taken postmortem from AD patients by RT-PCR analysis. The donors of fibroblasts consisted of 28 cases with AD and 19 neurological patient without dementia (CTL). The brains came from 17 cases with AD and 23 cases with CTL. We found that PS-1 mRNA levels in skin fibroblasts of AD patients were significantly higher than those of CTL patients (p < 0.0001). Moreover, we found that PS-1 mRNA levels in human brains with AD were significantly higher than in those with CTL (p < 0.0001). These findings suggest that high levels of PS-1 mRNA in AD may play an important role in developing AD and that the examination of PS-1 mRNA in skin fibroblasts may be helpful for the diagnosis of AD.

Aged↗
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High expression of apolipoprotein E mRNA in the brains with sporadic Alzheimer's disease.

In order to study progressive dementia in Alzheimer's disease (AD) patients, we analyzed the gene expression of apolipoprotein E (apoE). ApoE mRNA level in the brains of patients with AD was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. ApoE genotype and the promoter polymorphisms (-491A/T, Th1/E47cs) were determined by the PCR restriction fragment length polymorphism method. The apoE mRNA level was significantly higher in the AD group than the control group (p < 0.05). ApoE mRNA in the AD group with apoE epsilon 4 was also significantly higher than that in the control group with apoE epsilon 4 (p < 0.05). Our result did not indicate the possibility that the promoter polymorphisms modulate the apoE mRNA level. The higher level of apoE mRNA in AD with apoE epsilon4 may play an important role in the development of AD.

Aged↗
PubMedDate not supplied

Analysis of amyloid precursor protein mRNAs in skin fibroblasts in Down's syndrome.

We examined amyloid precursor protein (APP) mRNAs expression in skin fibroblasts from Down's syndrome (DS) patients of different ages to determine the time of occurrence of abnormal splicing. The ratio of APP770 + 751 mRNA to APP695 mRNA (APP770 + 751/695) was significantly increased in the young DS group and adult DS group compared with the age-matched control groups (p < 0.01, p < 0.05), but no significant increase was observed in the aged DS group compared with the age-matched control group. These findings suggest that metabolic abnormalities of the APP gene occur at a very early stage of DS, at a mean age of about 5 years. Therefore, metabolic abnormalities of the APP gene are considered to appear at a very young age also Alzheimer's disease (AD). In this study, we confirmed that examination of the APP gene in skin fibroblasts might be useful for early diagnosis of AD.

Adult↗
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Heat shock protein 70 mRNA levels in mononuclear blood cells from patients with dementia of the Alzheimer type.

The heat shock protein 70 (HSP70) gene is located in chromosome 14, it is now considered as a molecular 'chaperone' and a cell-protective agent. It may be closely related to the pathogenesis of dementia of the Alzheimer type (DAT). To examine the relationship between HSP70 and DAT, HSP70 mRNA expression levels in mononuclear blood cells (MBCs) from patients with DAT were measured by Northern blotting. We found no significant correlation between HSP70 mRNA levels and aging. We found that HSP70 mRNA levels in MBCs from patients with DAT were significantly lower than those from patients with vascular dementia and nondemented controls. These findings suggest that the lower levels of constitutive HSP70 mRNA in DAT play an important role in developing DAT and that the measurement of HSP70 mRNA may be useful for the diagnosis of DAT.

Aged↗
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An epidemiologic study of cerebrovascular disease in western Japan: with special reference to transient ischemic attacks.

The prevalence and incidence ratios of cerebrovascular disease, with special reference to transient ischemic attack (TIA), were studied in the towns of Daisen and Ama in western Japan. There have been no previous reports on this subject in Japan. The prevalence ratios of TIA were estimated to be 4.4 in Daisen and 2.0 in Ama per 1,000 people over 40 years old. The ratio of carotid arterial system TIA to vertebrobasilar arterial system TIA was about 1 to 1. The incidence ratios of stroke were 319.6 in Daisen and 314.5 in Ama per 100,000 people of all ages. The prevalence ratios of stroke were estimated to be 14.8 in Daisen and 13.5 in Ama per 1,000 people of all ages. The prevalence ratio of TIA in Japan is about one-third to one-half of that in Western countries. However, the prevalence of complete stroke is much higher in Japan compared with that in Western countries. Therefore, the ratio of TIA to stroke is much lower in Japan than in Western countries. The obstruction of small intracranial arteries, in addition to heart disease, might play an important role in TIA in Japan, whereas in Western countries TIA might be mostly caused by heart disease or the atherosclerosis of extracranial arteries.

Adult↗