Biomedical subjects

Tomio Arai

Publications and source records attributed to Tomio Arai.

48 records · Page 3Linked to original sources

PubMed2003

Accumulation of phosphorylated alpha-synuclein in aging human brain.

Alpha-synuclein in Lewy bodies (LBs) is phosphorylated at Ser129. We raised monoclonal and polyclonal antibodies to this phosphorylation site (psyn) and examined 157 serial autopsy brains from a geriatric hospital. Anti-psyn immunoreactivity was observed in 40 of these cases (25.5%). Immunohistochemistry revealed 4 novel types of pathology: diffuse neuronal cytoplasmic staining (pre-LB); neuropil thread-like structures (Lewy threads); dot-like structures similar to argyrophilic grains (Lewy dots); and axons in the white matter (Lewy axons). This novel pathology was abundantly present around LBs and also involved the limbic subcortical white matter, the cerebral cortical molecular layer, and the spongiform changes of the medial temporal lobe associated with cases of dementia with LBs (DLB). The phosphorylated alpha-synuclein was limited to the temporal lobe in cases of Parkinson disease, spread from the temporal lobe to the frontal lobe in cases of DLB transitional form and further spread to the parietal and occipital lobes in DLB neocortical form. Our findings suggest that LB-related pathology initially involves the neuronal perikarya, dendrites, and axons, causes impairment of axonal transport and synaptic transmission, and later leads to the formation of LBs, a hallmark of functional disturbance long before neuronal cell death.

Aged↗

PubMed2003

Increased pulse wave velocity associated with reduced calcaneal quantitative osteo-sono index: possible relationship between atherosclerosis and osteopenia.

Although the associations between arterial calcification or advanced atherosclerosis and osteopenia have been well documented, it is not clear whether the one is the result of the other or they coprogress from the early stages through common mechanisms. Thus, we measured pulse wave velocity (PWV), which reflects earlier phase atherosclerosis, and osteo-sono assessment index (OSI), which correlates with bone mineral density, in 7865 Japanese subjects (4183 males and 3682 females, aged 50 +/- 12 yr) and analyzed their association. PWV was determined by the volume rendering method; OSI was measured by the calcaneal quantitative ultrasound method. We evaluated the influence of age, gender, menopausal state, and established atherosclerotic risk factors on this association. In a linear regression analysis, OSI negatively correlated with PWV in both genders, and this association was more prominent in females (r = -0.38, P < 0.01) than in males (r = -0.17, P < 0.01). In females, this relationship was stronger after the menopause. In a multivariate analysis, PWV was significantly associated with OSI independent of age and conventional atherosclerotic risk factors. In females, this association was independent from menopause. These results suggest that common or related mechanisms, which may be accelerated after menopause, control both atherosclerosis and osteoporosis from the early stages.

Adult↗

PubMed2003

Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk.

The measurement of brachial-ankle pulse wave velocity (baPWV) is simple and applicable for general population studies. The present study was conducted to evaluate the applicability of baPWV for screening cardiovascular risk as well as for use as a marker of the severity of atherosclerotic vascular damage in a general population. baPWV was measured in a cross-sectional study involving two cohorts constituting a total of 10,828 subjects who underwent annual health screening check up examinations (6,716 males and 4,112 females; age 30 to 74 years). The Framingham risk score and Pocock's score were obtained. Multivariate analysis demonstrated that baPWV was associated with both scores, independently from conventional atherosclerotic risk factors. The receiver-operator characteristic curve demonstrated that a baPWV of 14.0 m/s is useful for risk stratification by Framingham score and to discriminate patients with either stroke or coronary heart disease (n=143), but the likelihood ratios were less than 5.0. Logistic regression analysis demonstrated that a baPWV>14.0 m/s is an independent variable for the risk stratification by Framingham score and for the discrimination of patients with atherosclerotic cardiovascular disease. Thus, baPWV has potential as a new marker of cardiovascular risk and may be more useful than other conventional markers; in addition, baPWV is easy to obtain and serves as an indicator of either atherosclerotic cardiovascular risk or severity of atherosclerotic vascular damage; thus it is useful to screen the general population. While the discriminating powers are not sufficiently high, a cutoff value of 14.0 m/s serves to screen subjects, especially in middle-aged ones, of either gender.

Adult↗

PubMed2003

Nomogram of the relation of brachial-ankle pulse wave velocity with blood pressure.

The present study was conducted to make a nomogram of the relation of brachial-ankle pulse wave velocity (baPWV) with blood pressure. In 11,375 subjects (age range: 30 to 79 years) in whom we measured baPWV, multivariate linear regression analysis demonstrated that age, systolic blood pressure, and gender were significant determinants of baPWV. Of them, we selected 5,302 subjects (2,630 men and 2,672 women, age 46 +/- 11 years) with either normal blood pressure or with high blood pressure without other atherosclerotic risk factors. Using data from these subjects, we tried to make an age-derived nomogram and a systolic blood pressure-derived nomogram for in both genders. The regression curve analysis demonstrated significant quadratic curves for both associations. The obtained nomograms were applied to 297subjects with coronary heart disease. Their measured baPWV (1,569 +/- 344 cm/s) was significantly higher than the values calculated from the age-derived nomogram (1,502 +/- 241 cm/s) and the systolic blood pressure-derived nomogram (1,418 +/- 236 cm/s) (p < 0.01). Thus, a nomogram of the relation of baPWV with blood pressure was obtained. The comparison of the measured baPWV with the values calculated from the nomograms may be useful to not to underestimate the real risk for atherosclerotic cardiovascular diseases, including the severity of atherosclerotic vascular damage, reflected by measured baPWV in subjects with different blood pressure levels.

Adult↗

PubMed2003

[Marked decrease of intracranial atherosclerosis in contrast with unchanged coronary artery stenosis in Japan].

We conducted comparative studies on intracranial atherosclerosis and coronary artery stenosis over the past 28 years. Two-year consecutive autopsy case studies from an urban geriatric hospital between 1974-1975 (Group I. 484 cases). 1986-1987 (Group II, 504 cases) and 2000-2001 (Group III, 273 cases) were employed. Atherosclerotic changes of the bilateral middle cerebral arteries and basilar artery were semiquantitatively evaluated as none (0), mild (1), moderate (2) and severe (3) and values of the 3 arteries were totalled to give a value of 0-9 which was taken as the intracranial atherosclerotic index (ICAI). The coronary stenotic index was calculated as previously reported (Sugiura et al 1969). ICAI and CSI were directly compared with each other, together with risk factors for each, including mean blood pressure (BP), serum level of total cholesterol (Tch) and the history of diabetes mellitus (DM+). Chronologically ICAI decreased dramatically but CSI did not change at all. There was continuous lowering of BP, elevation of Tch and increased incidence of DM+. There was a significant positive correlation in BP in relation to both ICAI and CSI (p < 0.01). DM+ vs. CSI (p < 0.01) and ICAI (p < 0.05), and Tch vs. CSI (p < 0.01) but not ICAI. Regression analysis highlighted age and BP as major risk factors for ICAI. Our study provides the first morphological confirmation of marked decrease of the intracranial atherosclerosis in the recent 28 years, in contrast with unchanged coronary stenosis in Japanese elderly subjects.

Aged↗

PubMed2003

[Free/total prostate specific antigen ratio (%PSA) to predict probability of prostate cancer].

It has been reported recently that %PSA, the ratio of free-PSA(F-PSA) and total-PSA(T-PSA), remains significantly lower in sera of patients with prostatic cancer(PCA) than there in cases with benign prostate hypertrophy(BPH). We examined %PSA can be used for differential diagnosis of PCA from BPH. Forty-seven non-treated Japanese patients with prostate problem were examined for PSA assays and biopsy. On biopsy, 25 cases were diagnosed as PCA, and 22 cases as BPH. On T-PSA value, there were 18 cases of PCA and 8 cases of BPH whose T-PSA values were over 10 ng/ml. When %PSA was studied, cases with less than 15% of %PSA were found to be PCA exclusively(16/16), while cases with less than 20 of %PSA included 19 PCAs and 4 BPHs. In 17 PCA patients with stage B to stage D, the %PSA was less than 20 except one case. T-PSA was examined in 88 cases at the checkup in our old age home. Four samples of which T-PAS levels were in gray zone, were assayed for %PSA. Two of them, with %PSA values less than 20 ng/ml, were found to be PCA, while the remaining two, with %PSA over 20 ng/ml, were BPH.

Aged↗

PubMed2002

Telomere lengths are characteristic in each human individual.

BACKGROUND: A great deal of attention has been focused on telomeres in relation to cellular aging, immortality, and cancer. However, there is no simple link between telomeres and tissue turnover. We recently proposed a hypothesis that telomere shortening with aging and telomere lengths in different organs are characteristic for human individuals. METHODS: To test this, telomere lengths were measured using DNA from cerebral cortex, myocardium, liver, renal cortex and spleen tissues obtained from human subjects ranging in age from neonates to centenarians. RESULTS: Regression analyses demonstrated telomere reduction rates of 29-60 base pair (bp) per year in the liver, renal cortex and spleen, but no such decrease in the cerebral cortex and myocardium. Significant correlation was found between tissues within individuals, such as cerebral cortex versus (vs) myocardium, cerebral cortex vs liver, cerebral cortex vs renal cortex, myocardium vs liver, myocardium vs renal cortex, and liver vs renal cortex. In most cases, the longest telomeres were observed in the myocardium and the shortest in the liver or renal cortex. CONCLUSIONS: Telomere lengths did not show clear correlation with tissue renewal times in vivo, but rather were characteristic for individuals.

Adolescent↗

PubMed2002

Incidence of apoptosis increases with age in colorectal cancer.

The incidence of cancer increases with advancing age, but the biological behavior of cancer is known to be less aggressive in elderly people. Thus, the proliferative activity and extent of apoptosis of cancer cells were assessed in samples from 163 cases of colorectal cancer focusing on the age of patients, using Ki-67 labeling index (LI) and apoptotic index (AI) by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end labeling method and staining for activated caspase-3. The Ki-67 LI of colorectal cancer ranged from 2.33 to 80.4% (mean 32.2%), while the AI ranged from 0.00 to 14.8% (mean 3.57%). Concerning the aging effect, linear and positive correlations were found for the Ki-67 LI of cancer with age (p<0.05) and the AI of cancer with age (p<0.05). However, in normal colorectal mucosa, aging of patients revealed a significant correlation only with the AI but not with the Ki-67 LI. The AI in earlier stages of cancers (stages 0 and 1) revealed a significant difference between younger cases (age<65) and more elderly cases (age>/=65) (p<0.05), however, the Ki-67 LI did not exhibit a significant difference. Therefore, an increased frequency of apoptosis in colorectal cancer tissues, especially in the earlier stages, may possibly explain the slower growth of colorectal cancers in the elderly. Next, the expressions of several regulatory molecules for the proliferation/apoptosis of tumor cells were determined. The results demonstrated a tendency for stronger and more frequent expressions of c-myc, Bak and Bax despite a rather weaker expression of Bcl-2 in cancer tissues from the elderly compared with those from the younger patients. The potential roles of these regulatory molecules on age-change in the proliferation/apoptosis of colorectal cancers are discussed.

Adenocarcinoma↗

PubMed2002

Comparative analysis of telomere lengths and erosion with age in human epidermis and lingual epithelium.

We investigated progressive telomere shortening in normal human epidermis and lingual epithelium during aging, and attempted, in particular, to ascertain whether the telomere shortening that accompanies aging occurs at the same rate in different tissues. We studied telomeric DNA integrity, and estimated annual telomere loss, in 52 specimens of epidermis and 48 specimens of lingual epithelium collected at autopsy from subjects who had died at ages between 0 and 101 y. Most of the DNA samples were measured twice by southern blot hybridization. In addition, the correlation between telomere lengths in the two types of tissues was examined. The telomere reduction rates in epidermis and lingual epithelium were 36 bp and 30 bp per y, respectively, and these were significantly different. The rates obtained by the second measurements in epidermis and lingual epithelium were 39 and 32 bp per y, respectively, and these were also significantly different. The mean telomere lengths in the epidermis of eight neonates and the lingual epithelium of seven neonates were 13.2+/-1.0 and 13.8+/-1.0 kb, respectively. Comparison of telomere lengths in the two tissues for 41 paired samples showed that the mean telomere length in the epidermis (10.7+/-2.3 kb) was less than that in the lingual epithelium (12.4+/-2.5 kb); however, statistical analysis revealed a very significant relationship between epidermal and lingual epithelial telomere length (r=0.842, p<0.0001). These results indicate that the telomeres in epidermis and lingual epithelium are characterized by tissue-specific loss rates.

Adolescent↗

PubMed2002

Oncocytic adenocarcinoma of the stomach: parietal cell carcinoma.

We report 10 cases of an unusual type of gastric adenocarcinoma that occurred in elderly patients 58-81 years of age. Histologically, the tumors were well to moderately differentiated tubular adenocarcinomas with very eosinophilic, finely granular cytoplasm. Immunohistochemical stains for antimitochondrial antibody were strongly positive. Ultrastructurally, the tumor cells had numerous mitochondria in their cytoplasm and occasional intracytoplasmic lumina with associated long microvilli. These histologic and ultrastructural features are similar to those of parietal cells in normal gastric fundic mucosa, but immunohistochemical staining of the tumors using four different antiparietal cell antibodies (anti-H(+)-K(+)-adenosine triphosphatase antibodies) was negative in all cases. Therefore, we think that these tumors were not parietal cell carcinomas but could be termed oncocytic adenocarcinomas, or adenocarcinomas with oncocytic differentiation. Previously reported cases of parietal cell carcinoma have been said to have a favorable prognosis, but it will be necessary to study a larger number of cases to determine the prognosis of oncocytic adenocarcinoma.

Adenocarcinoma↗

PubMed2002

Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement.

The present study was conducted to evaluate the validity and reproducibility of noninvasive brachial-ankle pulse wave velocity (baPWV) measurements and to examine the alteration of baPWV in patients with coronary artery disease (CAD). Simultaneous recordings of baPWV by a simple, noninvasive method and aortic pulse wave velosity (PWV) using a catheter tip with pressure manometer were performed in 41 patients with CAD, vasospastic angina, or cardiomyopathy. In 32 subjects (15 controls and 17 patients with CAD), baPWV was recorded independently by two observers in a random manner. In 55 subjects (14 controls and 41 patients with CAD), baPWV was recorded twice by a single observer on different days. baPWV were compared among 172 patients with CAD (aged 62 +/- 8 years); 655 age-matched patients without CAD but with hypertension, diabetes mellitus, or dyslipidemia; and 595 age-matched healthy subjects without these risk factors. baPWV correlated well with aortic PWV (r=0.87, p<0.01). Pearson's correlation coefficients of interobserver and intraobserver reproducibility were r=0.98 and r=0.87, respectively. The corresponding coefficients of variation were 8.4% and 10.0%. baPWV were significantly higher in CAD patients than in non-CAD patients with risk factors, for both genders (p<0.01). In addition, baPWV were higher in non-CAD patients with risk factors than in healthy subjects without risk factors. Thus, the validity and reproducibility of baPWV measurements are considerably high, and this method seems to be an acceptable marker reflecting vascular damages. baPWV measured by this simple, noninvasive method is suitable for screening vascular damages in a large population.

Adult↗

PubMed2002

[Diagnosis of effort angina pectoris at rest by first derivative electrocardiography].

OBJECTIVES: First derivative electrocardiography (FDECG) records the slope of the wave of the standard 12-lead electrocardiography (ECG) and enables quantification of ECG-T wave symmetry. This study investigated the usefulness of FDECG to diagnose effort angina pectoris in patients with chest pain. METHODS: All 62 patients who visited our hospital with exertional chest pain underwent FDECG at rest, and exercise electrocardiography or stress thallium scintigraphy. Patients with possible ischemic change underwent coronary angiography, and those with significant coronary artery stenosis (> or = 75% reduction) were classified as the angina pectoris group (23 subjects). The other patients (without ischemic change or without significant coronary artery stenosis) formed the non-angina pectoris group (39 subjects). The FDECG is a simple differential wave with two peaks. The first peak of the FDECG-T wave designated as the T1 wave and the second peak as the T2 wave. The heights (the T1 and T2 wave amplitude) and the T2/T1 ratio (T2 wave heights/T1 wave heights) were calculated in the two groups. RESULTS: The T2/T1 ratios in leads I, V3, V4, V5 and V6 were significantly (I, V3, V4: p < 0.01, V5: p < 0.0001, V6: p < 0.001) decreased in the angina pectoris group. Using the criterion of a T2/T1 ratio at the V5 lead of less than 1.30, FDECG could detect effort angina pectoris patients with 65% in sensitivity, 74% specificity and 71% accuracy. CONCLUSIONS: ECG-T waves in the angina pectoris group were symmetrical. T2/T1 ratio of the FDECG-T wave is a useful index to diagnose effort angina pectoris at rest.

Angina, Unstable↗