Biomedical subjects

Tomio Arai

Publications and source records attributed to Tomio Arai.

At least 37 records · Page 2Linked to original sources

PubMed2005

[Biopsy methods and pathology of Barrett's esophagus].

We reviewed the definition of the esophagogastric junction and the biopsy sites and histologic findings of biopsy specimens from Barrett's esophagus. The borderline between the esophagus and stomach has been defined as the distal limit of the longitudinal vessels by the Japan Esophageal Society, because the longitudinal vessels are always located within the esophagus. As squamous islands in Barrett's mucosa are usually the orifices of esophageal glands proper, biopsy specimens from the squamous islands show esophageal glands proper or their ducts. The identification of esophageal glands proper is a definite histological indicator that a piece of biopsy tissue is of esophageal origin. Therefore, a diagnosis of Barrett's esophagus can be made purely on the basis of the histologic findings in these biopsy specimens of squamous islands. Since columnar mucosa is usually recognizable at endoscopy, a diagnosis of Barrett's esophagus can be made solely on the basis of endoscopic examination, without any need for histologic confirmation, if squamous islands are recognized in columnar-lined mucosa.

Barrett Esophagus↗

PubMed2004

Aortic pulse wave velocity and the degree of atherosclerosis in the elderly: a pathological study based on 304 autopsy cases.

INTRODUCTION: Studies examining the correlation between aortic pulse wave velocity (PWV) and atherosclerosis have reported conflicting results. The present paper verifies this correlation by conducting autopsy examination of elderly subjects. METHODS: A total of 3456 PWV examinations had been performed on 1538 elderly people, as a part of routine physical check-up. During long-term follow-up, many of these subjects died, and autopsy study could be conducted on 304 of these subjects. The average age at death of the subjects was 83 years and the male: female ratio was 6:5. The pathological atherosclerotic index (PAI) was defined as the average pathological degree of atherosclerosis in eight large arteries, including aorta. RESULTS: Significant positive correlations were observed between the age and PWV (gamma=0.273, P<0.001), and between the systolic blood pressure and PWV (gamma=0.478, P<0.001). There was a significantly positive correlation between the aortic atherosclerotic degree and mean PWV (rho=0.239, P<0.005), and between the PAI and mean PWV (gamma=0.323, P<0.001). The partial regression coefficient between the PAI and mean PWV was 0.209, after adjusting for the mean systolic blood pressure and age at death. CONCLUSION: The present study proved a weak correlation between the PWV and the pathologically verified degree of the aortic and systemic atherosclerosis.

Age Factors↗

PubMed2004

Cancer and aging: symposium of the 27th annual meeting of the Japanese society for biomedical gerontology, Tokyo.

Although many hypotheses have been proposed to explain the strong link between aging and cancer, the exact mechanisms responsible for the increased frequency of occurrence of cancer with advancing age have not been fully defined. Recent evidence indicates that malregulation of the apoptotic process may be involved in some aging process as well as in the development of cancer. Although it is still under debate how apoptosis is expressed during aging in vivo, this phenomenon is an important factor in unwinding the complicated mechanisms that link cancer and aging. In this review, we report on the discussion at the symposium of the 27th annual meeting of the Japanese society for biomedical gerontology, regarding recent findings from aging and carcinogenesis studies using animal models, the characteristics of cancer in patients with Werner's syndrome, the epigenetic changes in human cancers and aging, and the characteristics of human cancers in the elderly. It was concluded that apoptosis plays a role in the aging process and carcinogenesis in vivo, likely as an inherent protective mechanism against various kinds of damages to genes/chromosomes.

Aging↗

PubMed2004

Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles.

Estrogen receptor alpha (ERalpha) may be implicated in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to clarify the association between ERalpha gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, PvuII (P or p) and XbaI (X or x), of the ERalpha gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r = 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E epsilon4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between PvuII polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the epsilon4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the epsilon4 allele was the next strongest, and PvuII polymorphism was the third strongest (p < 0.0001, R(2) = 0.144). The XbaI polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the PvuII polymorphism of the ERalpha gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the epsilon4 allele.

Aged↗

PubMed2004

In situ detection of apolipoprotein E epsilon 4 in archival human brain.

A monoclonal antibody specific to apolipoprotein E 4 (apoE4) was applied immunohistochemically to archival human brain tissue. The examined 30 cases comprised four epsilon/epsilon4, 10 epsilon3/epsilon4, one epsilon2/epsilon4, 10 epsilon3/epsilon3 and five epsilon2/epsilon3 genotypes. The anti apoE4 antibody visualized senile plaques, neurofibrillary tangles and reactive astrocytes, as well as serum in the blood vessels and vascular smooth muscle cells in the cases of epsilon4. Moreover, the staining intensity was stronger in the cases carrying the epsilon4 homozygosity than in those cases of epsilon4 heterozygosity. Specific immunoreactivity was not obtained in those cases not carrying the epsilon4 allele. This method will allow in situ detection of apoE epsilon4 and contribute to studies of the effect of epsilon4 on Alzheimer's disease.

Alleles↗

PubMed2004

Pathologic characteristics of gastric cancer in the elderly: a retrospective study of 994 surgical patients.

BACKGROUND: The clinicopathologic features of gastric carcinoma in elderly people have been reported previously. The present study examined the patterns and distribution of gastric carcinomas in the elderly, especially in patients aged 85 and older. METHODS: A retrospective study of 994 consecutive Japanese patients aged 65 years or older was performed. In this group, a total of 1,147 lesions were analyzed. Pathological findings in the very old group (older than 85 years; n = 126) were compared with those in younger groups (65-74 years [young-old group]; n = 356) and (75-84 years [middle-old group]; n = 512). RESULTS: While the male-to-female ratio significantly decreased with advancing age, the relative odds of gastric cancer in men were higher than those in women in all age groups. In the very old group, cancer of the lower third of the stomach tended to increase with advancing age, and accounted for 43.7% of cases. In the population overall, differentiated-type adenocarcinoma accounted for 89.6% in the early cancers and 50.3% in the advanced cancers. The proportion of cases involving differentiated-type carcinoma significantly increased with advancing age in early cancer and female advanced cancer cases, whereas no significant change was found in male advanced-cancer patients. In the very old group, lymph node metastasis was found in 5.4% of early cancers and 72.7% in advanced cancers. Multiple cancers significantly increased with advancing age ( P < 0.05; 10.7% in the younger-old group, 12.7% in the middle-old group, and 19.0% in the very old group). CONCLUSION: These results indicate that, in the very old group, gastric cancers showed a distal shift with predominantly differentiated-type carcinoma in the early stages and increased undifferentiated-type carcinomas in advanced stages. These results suggest increased histologic diversity with tumor growth. These findings have important implications for the screening and diagnosis of gastric cancer in the elderly.

Adenocarcinoma↗

PubMed2004

The relationship between high-sensitive C-reactive protein and pulse wave velocity in healthy Japanese men.

Although pulse wave velocity (PWV) and high-sensitive C-reactive protein (hsCRP) are known as predictors of future cardiovascular events, their association has not been examined. The present study was conducted to evaluate their association in the general population. In 2668 Japanese men (43 +/- 10 years old), PWV was obtained by volume rendering methods, and hsCRP was determined by the latex aggregation method. PWV showed a significant correlation with logarithm of hsCRP (r = 0.06, P < 0.01). The concentration of hsCRP in the highest quartile of PWV was higher than that in the other three groups (P < 0.01). However, multiple linear regression analyses demonstrated that logarithm of hsCRP was not significantly related to PWV, independent from conventional risk factors. Calculated Framingham risk score (FRS) was higher in the highest quartiles of both hsCRP and PWV than in the other groups (P < 0.05). Thus, while increased hsCRP related to increased PWV, they may be independent predictors of atherosclerotic cardiovascular risk. A prospective study to confirm the independency of their significance in predicting future cardiovascular events and to evaluate the usefulness of the combination of both parameters to screen subjects for cardiovascular risk is necessary.

Adult↗

PubMed2004

Developments of geriatric autopsy database and Internet-based database of Japanese single nucleotide polymorphisms for geriatric research (JG-SNP).

To facilitate geriatric research on the roles of genetic polymorphisms of candidate genes, two databases were developed based on data obtained from autopsy examinations of elderly subjects: the geriatric autopsy database (GEAD) and the Japanese single nucleotide polymorphisms (SNP) database for geriatric research (JG-SNP) which is accessible on the Internet (http://www.tmgh.metro.tokyo.jp/jg-snp/english/E_top.html). The data for the GEAD were derived from 1074 consecutive autopsy cases (565 male and 509 female cases) with an average age of 80 years. The GEAD was installed on a stand-alone Windows 2000 server using Oracle 8i as the database application. The GEAD contains clinical diagnoses of 26 geriatric diseases, histories of smoking and alcohol consumption, pathological findings (720 items), severity of atherosclerosis, genetic polymorphism data, etc. On the JG-SNP website, case distribution corresponding to a specified SNP or disease can be searched or downloaded. Although there are several Internet-based SNP databases such as dbSNP, no databases are available at present on the web that contain both SNP data and phenotypic data. As autopsy studies can provide large amounts of accurate medical information, including the presence of undiagnosed diseases such as latent cancers, the GEAD is a unique and excellent database for research on genetic polymorphisms.

Aged↗

PubMed2004

Hypermethylation of the hMLH1 promoter with absent hMLH1 expression in medullary-type poorly differentiated colorectal adenocarcinoma in the elderly.

To clarify the significance of hMLH1 promoter hypermethylation in the development of medullary-type poorly differentiated colorectal adenocarcinoma, we studied the status of promoter methylation and hMLH1 expression in 23 medullary-type and 12 pleomorphic-type carcinomas, as well as the pathology and microsatellite status. In medullary-type carcinomas, the percentages of cases with promoter methylation (83%) and an absence of hMLH1 expression (91%) were significantly higher than in pleomorphic-type carcinomas (14 and 17%), respectively. The rate of microsatellite instability in the medullary type was significantly higher than that of the pleomorphic type (87 vs 40%, P<0.01). Compared with pleomorphic-type carcinomas, medullary-type carcinomas were significantly associated with hMLH1 promoter methylation, absent expression of hMLH1 protein, microsatellite instability, as well as a proximal location, a Crohn's-like lymphoid reaction, a low incidence of lymph node metastasis, and a favorable outcome. Medullary-type carcinomas accumulated with advancing age, especially in the female. These results indicated that hMLH1 hypermethylation, concurrent with a lack of its protein expression, may play an important role in the development of medullary-type poorly differentiated colorectal adenocarcinomas in the elderly.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Lewy body-related alpha-synucleinopathy in aging.

To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging, we investigated the incidence of LBs in 1,241 consecutive autopsy cases (663 males and 578 females). LB pathology was identified histologically in sections stained with hematoxylin and eosin and with anti-ubiquitin and anti-alpha-synuclein antibodies. Cases without LBs were classified as LB stage 0 (987 cases). Cases with LBs were classified as follows: LB stage I = incidental LBs (149 cases); LB stage II = LB-related degeneration without attributable clinical symptoms (47 cases); LB stage III = Parkinson disease without dementia (10 cases); LB stage IV = dementia with Lewy bodies (DLB) transitional (limbic) form (25 cases); and LB stage V = DLB neocortical form (23 cases). The average age at death was greater for those cases with LBs. There were no gender differences in the LB pathology. G842A polymorphism in the paraoxonase I gene was associated with men in LB stage II or above and suggests a gender-specific risk factor. LB stage V had higher stages of neurofibrillary tangle and senile plaque involvement and also had a higher frequency of apolipoprotein E epsilon4. Our findings indicate that LBs are associated with cognitive decline, either independently or synergistically with neurofibrillary tangles and senile plaques.

Age Factors↗

PubMed2004

Staging of argyrophilic grains: an age-associated tauopathy.

We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age. The distribution of AGs followed a stereotypic regional pattern. Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases without other dementing pathology were classified as 0.5 or higher in the clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II. No association with apoE genotyping was detected. Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly.

Adult↗

PubMed2004

The age-related increase in arterial stiffness is augmented in phases according to the severity of hypertension.

Although blood pressure and age are major determinants of arterial stiffness, it is still unclear whether age-related changes in arterial stiffness are similar among subjects with different degrees of severity of hypertension. The present study examined the association between age and pulse wave velocity in subjects with different degrees of hypertension stratified according to the JNC-7 classification (Normal, Prehypertensive, and Stage I or II Hypertensive subjects). A number of 5,312 subjects (age range, 30-79 years) with no atherosclerotic risk factors other than high blood pressure were selected from two cohorts who regularly underwent annual health checkups, including the measurement of brachial-ankle pulse wave velocity (baPWV). baPWV was increased according to the severity of hypertension in all age groups. The association between age and baPWV formed a quadratic curve in each stage in both genders. The steepness of the slope of the quadratic curve increased according to the severity of hypertension. In each stage of hypertension, age and the baPWV were divided into tertiles. After adjustment for systolic and diastolic blood pressure, the odds ratio of having an increased baPWV in the 3rd age tertile (the highest-age group) was found to increase according to the severity of hypertension. In conclusion, the age-related increase of baPWV was shown to be augmented in phases according to the severity of hypertension, and this augmentation occurred even between the Normal and Prehypertensive stages. These results support the JNC-7 recommendations for a strict control of blood pressure even in the elderly.

Adult↗

PubMed2004

[Effects of acute administration of beraprost sodium on parameters related to atherosclerotic vascular damage in coronary artery disease].

OBJECTIVES: The present study was conducted to examine the effects of acute administration of prostacyclin derivatives on plasma levels of adhesion molecules, endothelial function, and pulse wave velocity in patients with coronary heart disease. METHODS: In 20 patients with coronary heart disease, plasma levels of vascular cell adhesion molecule-1, P-selectin, and beta-thromboglobulin, endothelial function, and pulse wave velocity were assessed before and after the cold pressor test. These assessments were performed again 2 hr after the oral administration of prostacyclin derivatives (beraprost sodium 40 micrograms) or placebo. Endothelial function was assessed by changes in forearm blood flow before and after reactive hyperemia. Pulse wave velocity was determined by the volume rendering method. RESULTS: Prostacyclin derivatives significantly improved endothelial function and decreased plasma beta-thromboglobulin level, but did not affect blood pressure and pulse wave velocity. Prostacyclin derivatives did not prevent the elevations of blood pressure and pulse wave velocity induced by the cold pressor test, but did prevent the elevations of P-selectin and beta-thromboglobulin induced by the cold pressor test. CONCLUSIONS: Prostacyclin derivatives improved endothelial function and prevented platelet activation induced by the cold pressor test. Prostacyclin apparently has an anti-atherogenic effect.

Aged↗

PubMed2003

Early pathogenesis of cardiac amyloid deposition in senile systemic amyloidosis: close relationship between amyloid deposits and the basement membranes of myocardial cells.

Despite a number of in vitro studies of transthyretin (TTR) amyloidogenesis the early stage of in vivo amyloidogenesis in the human heart is largely unknown. A heart with a mild degree of cardiac amyloidosis removed from a 90-year old woman at autopsy was selected for analysis. The genotype of the TTR was the wild type. An immunohistochemical study with anti-TTR antibody was performed on serial paraffin sections, and 17 TTR-positive lesions less than 50 micro m in diameter consisting of 13 interstitial and 4 vascular lesions were identified. The early interstitial lesions start as thick membranous deposits between interfacing myocardial cells. They are Congophilic with green birefringence and positive for apolipoprotein E but negative for amyloid P component. The TTR-positive amyloid extends along intercellular spaces and becomes larger, involving several myocardial fibers. The media is the initial site of arteriolar involvement. According to the in vitro studies of amyloid fibrillogenesis, the most critical step is formation of the nucleus under supersaturated conditions. The supersaturated conditions are speculated to be achieved by binding to proteoglycans or lipid membranes. Our results indicate that the basement membrane of myocardial cells is the initial site of amyloid deposition, providing a suitable place for concentration of TTR.

Aged↗

PubMed2003

Age-related mitochondrial DNA deletion in human heart: its relationship with cardiovascular diseases.

BACKGROUND AND AIMS: Accumulation of damage to mitochondrial DNA (mtDNA) occurs in myocardial tissue with advancing age. However, despite higher incidence of cardiac diseases in the elderly, little attempt has been made to detect deletions of mtDNA in the myocardial tissue of aged individuals. The aim of the present study was to clarify the relationship between aging, mtDNA deletion and cardiovascular (CV) diseases. METHODS: We examined 163 autopsy cases, aged 60 years or older, using two different kinds of polymerase chain reaction (PCR): highly sensitive PCR to detect a common 4977-bp deletion and long-PCR for multiple deletions, which could be detected in case that deleted mtDNA accounted for more than several percents in total mtDNA. RESULTS: The common 4977-bp deletion was detected in 156 cases (95.7%), showing no significant difference among these age groups and no relation to CV diseases. By long-PCR, multiple deletions in cardiac mtDNA were found in 33 (20.2%) of 163 cases. The proportion of the mtDNA deletion in the nineties (46.2%) was significantly higher than those in the younger (15.3%, p < 0.05). Female predominance was significantly found in the group with the mtDNA deletion (p < 0.05). Multiple deletions of mtDNA were not significantly related to ischemic change, valvular diseases, left ventricular hypertrophy, congestive heart failure, coronary sclerosis, or heart weight except for right ventricular hypertrophy. CONCLUSIONS: These findings suggest that there is a close relationship between aging and deletion of mtDNA, and that the ratio of deleted mtDNA to total mtDNA increases with advancing age. Age-related deletion of mtDNA may have little influence on CV diseases except for right ventricular hypertrophy.

Aged↗

PubMed2003

Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement--a survey of 12517 subjects.

The present study was conducted to evaluate the influences of age and gender on the results of noninvasive brachial-ankle pulse wave velocity (baPWV). In 12517 subjects who had no medication and no history of cardiovascular diseases, multiple regression analysis demonstrated that age, blood pressure, body mass index, triglycerides, blood glucose, and uric acid were significant variables for baPWV in both genders. From this population, we extracted 7881 "healthy subjects" (4488 males and 3393 females, 25-87 years) without any of the atherogenic risk factors, and the results of baPWV were analyzed chronologically in 5-year age intervals. baPWV was lower in females than in males until age 60, and became similar in both genders over age 60. Multiple regression analysis demonstrated that not only the value of R(2) but also the coefficient of the effect of age on baPWV are larger in females than in males. In the estimation of the regression curve, the relationship between age and baPWV demonstrated a quadratic curve in both genders. Thus, aging influences baPWV, and its effect is more prominent in female. Menopause seems to be the crucial phenomenon to explain the augmented increase in arterial stiffness with aging in females.

Adult↗

PubMed2003

Hepatitis C virus seropositivity, but not hepatitis B virus carrier or seropositivity, associated with increased pulse wave velocity.

Immune mechanisms have important roles in the pathogenesis of atherosclerosis. The present study was conducted to evaluate the association of pulse wave velocity (PWV) with either hepatitis C or B. In 7514 subjects, we determined the PWV, as well as the plasma levels of hepatitis B virus antigen and antibody and of hepatitis C virus antibody. The results of multiple regression analysis showed that seropositivity for hepatitis C virus was a significant variable for PWV independent from atherosclerotic risk factors. Thus, hepatitis C virus seropositivity was associated with increased PWV.

Adult↗

PubMed2003

Adenoma, adenocarcinoma and mixed carcinoid-adenocarcinoma arising in a small lesion of the colon.

A unique tumor measuring 8 x 8 x 5 mm and composed of adenoma, adenocarcinoma and mixed carcinoid-adenocarcinoma arising in the ascending colon is reported. The mixed carcinoid-adenocarcinoma, in which adenocarcinomatous and carcinoid components intermingled, originated in the mucosa, penetrated the muscularis mucosa and extended into the submucosa. Immunohistochemically, carcinoid cells were positive for neuroendocrine markers and adenocarcinoma cells were intracytoplasmicly positive for carcinoembryonic antigen. Ultrastructurally, membrane-bound electron dense granules varying in shape, size and electron density were detected in the cytoplasm of carcinoid cells. No mutations of p53 and k-ras genes were detected in adenomatous, adenocarcinomatous or mixed carcinoid-adenocarcinoma components. The morphological appearances of the present case strongly suggests the histogenesis of this tumor in an adenoma-adenocarcinoma-carcinoid tumor sequence.

Adenocarcinoma↗