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Yoshiyuki Watanabe

Publications and source records attributed to Yoshiyuki Watanabe.

At least 19 recordsLinked to original sources
PubMed2007

Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer.

Epigenetic gene inactivation plays a key role in the development of various types of cancer. Using methylated CpG island amplification coupled with representational difference analysis to identify genes inactivated by DNA methylation in gastric cancer, we identified seven DNA fragments corresponding to the 5' CpG islands of the affected genes. One of the clones recovered was identical to the 5' flanking region of DFNA5, a gene previously shown to be associated with deafness and induced by DNA damage. Further analysis revealed that DFNA5 is expressed in normal tissues but is down-regulated in gastric cancer cell lines due to methylation of the region around its transcription start site. Treating gastric cancer cells that lacked DFNA5 expression with a methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored the gene's expression. Methylation of DFNA5 was detected in 50% of primary gastric tumors, and was correlated with positivity for Epstein-Barr virus and the absence of metastasis. Moreover, introduction of exogenous DFNA5 into silenced cells suppressed colony formation. Taken together, these data suggest that the silencing of DFNA5 occurs frequently in gastric cancer and may play a key role in development and progression of the disease.

Aged↗
PubMed2006

Clinicoradiological factors influencing the reversibility of posterior reversible encephalopathy syndrome: a multicenter study.

PURPOSE: The aim of this retrospective study was to clarify the relation between the reversibility of posterior reversible encephalopathy syndrome (PRES) with three factors: the anatomical region of the brain involved, the background clinical cause, and the diffusion weighted image (DWI) intensity of PRES lesions. MATERIAL AND METHODS: This multicenter study, conducted by the PRES Study Group of the Neuroradiology Workshop, involved 52 cases from 28 institutions. Initial and follow-up magnetic resonance imaging were compared regarding the reversibility of PRES lesions according to anatomical location and clinical background. Initial DWI and apparent diffusion coefficient (ADC) maps were reviewed in 20 cases. RESULTS: Reversibility was significantly lower (P < 0.01) in the brain stem (44%) and deep white matter (47%) compared to the other cortical and subcortical areas (76%-91%). The reversibility was greater in the eclampsia subgroup followed by the hypertension and chemotherapy subgroups. DWI, even with ADC maps, had limitations in predicting the outcome of PRES lesions. CONCLUSION: The typical cortical and subcortical PRES lesions showed reversibility, whereas the brain stem and deep white matter lesions showed less reversibility. PRES due to eclampsia showed maximum reversibility compared to hypertension- and drug-related PRES. DWI, even with ADC maps, had limitations in predicting the course of PRES.

Adolescent↗
PubMed2006

TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody.

Rheumatoid arthritis (RA) is characterized by hypertrophic synovial tissues comprising excessively proliferating synovial fibroblasts and infiltrating inflammatory cells. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell growth, inflammation and angiogenesis by acting on various cell types. In RA synovial tissues, TGF-beta is expressed at high levels. However, the precise role of TGF-beta in RA remains unclear. We herein demonstrated a causal link between the TGF-beta-induced RA synovial cell proliferation and induction of platelet-derived growth factor (PDGF)-AA. In addition, TGF-beta induced IL-6 and vascular endothelial growth factor (VEGF) production by RA synovial fibroblasts associated with nuclear factor-kappa B activation. These effects of TGF-beta on RA synovial fibroblasts were suppressed by TGF-beta type I receptor kinase inhibitor HTS466284. Furthermore, HTS466284 significantly prevented anti-collagen type II antibody-induced arthritis in mice according to the clinical manifestations, histology, tumor necrosis factor-alpha, PDGF and VEGF expression and 5-bromo-2'-deoxyuridine incorporation. These in vitro and in vivo results suggest that TGF-beta plays a role in the development of synovial hyperplasia consisting of synovial cell proliferation, inflammation and angiogenesis. The blockade of TGF-beta signaling may thus become an additional strategy for the treatment of RA.

Animals↗
PubMed2006

Serum total cholesterol levels and risk of mortality from stroke and coronary heart disease in Japanese: the JACC study.

The relation between serum total cholesterol and coronary heart disease is well established, but the relations with total stroke and stroke subtypes are controversial. We conducted a nested case-control study as part of the JACC study. A total of 39,242 subjects, 40-79 years of age, provided serum samples at baseline between 1988 and 1990. During the 10-year follow-up, 345 deaths from total strokes (including 76 intraparenchymal hemorrhages) and 150 deaths from coronary heart diseases were recorded. The control subjects were matched for sex, age, community, and year of serum storage, and further adjusted for systolic blood pressure, high density lipoprotein (HDL)-cholesterol, ethanol intake category, smoking status, and diabetes. Serum total cholesterol levels were measured using an enzymatic method. Cases with total stroke and more specifically intraparenchymal hemorrhage had lower mean values of serum total cholesterol levels compared with control subjects. The risk of mortality from intraparenchymal hemorrhage was significantly higher for persons with low total cholesterol levels [less than 4.14 mmol/l (160 mg/dl)] than with those with higher levels. The risk of mortality from coronary heart disease for persons with serum total cholesterol levels more than or equal to 6.72 mmol/l (260 mg/dl) was significantly higher than those with levels less than 4.14 mmol/l (160 mg/dl). Low serum total cholesterol levels are associated with high mortality from intraparenchymal hemorrhage while high levels are associated with high mortality from coronary heart disease among Japanese.

Adult↗
PubMed2006

Effectiveness of cervical cancer screening over cervical cancer mortality among Japanese women.

BACKGROUND: Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study. METHODS: Baseline survey of the Japan Collaborative Cohort Study for the enrollment of subjects was completed during 1988-90 and followed until 2003. This study only analyzed 63,541 women, aged 30-79 years, who were free from any cancer history at enrollment. RESULTS: During the follow-up period, 38 CC deaths were identified. The mean age at mortality was 67.0 years, with a mortality rate of 4.2 per 100,000 person-years. Participation rate in CC screening was 46.9%. Age-adjusted Cox model indicated significantly lower CC mortality [hazard ratio (HR) = 0.30, 95% confidence interval (CI) = 0.12-0.74] due to CC screening. Protectiveness remained almost the same (HR = 0.30, 95% CI = 0.12-0.76) when adjusted for age, body mass index and number of deliveries. The results also revealed that CC screening could reduce at least 50% of CC deaths even after excluding the effect of possible self-selection bias. CONCLUSIONS: CC screening in Japan may reduce CC mortality significantly for women aged 30-79 years. However, further studies with more CC deaths and increased statistical power are needed to validate the findings.

Adult↗
PubMed2006

Prospective cohort study of the risk of prostate cancer among rotating-shift workers: findings from the Japan collaborative cohort study.

Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.

Adult↗
PubMed2006

BCG vaccine elicits both T-cell mediated and humoral immune responses directed against mycobacterial lipid components.

The universe of antigens recognized by alphabeta T cells has recently been expanded to include not only major histocompatibility complex (MHC)-presented protein antigens but also CD1-presented lipid antigens. The significance of lipid-reactive T cells in host defense has been appreciated, using the guinea pig model of human tuberculosis. Here, we show that immunization with Mycobacterium bovis bacillus Calmette-Guerin (BCG), the commonly used anti-tuberculosis vaccine, induces activation of guinea pig cytotoxic T cells recognizing BCG lipids in the context of CD1 molecules. Further, BCG-immunized, but not mock-immunized, guinea pigs mount IgG antibody responses directed against lipoarabinomannnan, an essential cell wall lipid component of mycobacteria. These observations emphasize the ability of BCG to activate the host adaptive immunity to mycobacteria-derived lipids, which could potentially contribute to protection against tuberculosis.

Animals↗
PubMed2006

Quantitative study of changes in oxidative metabolism during visual stimulation using absolute relaxation rates.

In the context of quantitative functional MRI (fMRI), deoxyhemoglobin (dHb) content is the essential physiological parameter for calibrating the blood oxygenation level-dependent (BOLD) signal. In studies on humans, the baseline dHb content or its equivalent has been evaluated indirectly by means of carbon dioxide breathing as a physiological reference condition. In this study with normal volunteers, quantitative mapping of baseline dHb content was performed in a direct manner by measuring the reversible contribution of the effective transverse relaxation rate. The BOLD signal change in the visual cortex during 8 Hz flicker visual stimulation was calibrated based on the quantitative map of baseline dHb content. The calibrated relaxation rate change that represents the stimulation-induced fractional change of dHb content decreased by 14% within the activated visual cortex. Simultaneous measurement of cerebral blood flow (CBF) with BOLD showed an increase of 59%. From the calibrated relaxation rate and CBF changes, the cerebral metabolic rate of oxygen (CMRO2) was calculated to increase by 19-28% within the activated visual cortex. The ratio of the CBF increase to the CMRO2 increase was 2-3:1, which agreed well with results of similar quantitative fMRI studies for humans. The method proposed here for quantitative evaluation of the BOLD signal may be applicable not only to fMRI for normal human subjects, but also to physiologically altered or diseased states, because it requires no physiological perturbation.

Adult↗
PubMed2006

Safer endoscopic gastric mucosal resection: preoperative proton pump inhibitor administration.

BACKGROUND AND AIM: Control of bleeding is crucial in improving the safety of endoscopic mucosal resection (EMR), and intragastric acidity has a great impact on hemostasis and blood coagulation. Proton pump inhibitors (PPI) are potent suppressors of gastric acid; however, PPI need to be continuously administered orally for several days, and thus initial effects may be insufficient if PPI is only administered immediately after EMR. The aim of this study was to determine whether preoperative administration of PPI prior to EMR can elevate intragastric acidity, facilitate better control of intraoperative bleeding (complete coagulation and hemostasis), prevent postoperative bleeding, and facilitate healing of artificial ulcers. METHODS: A randomized clinical study was conducted in which EMR was performed with or without 1 week of preoperative PPI administration. RESULTS: Artificial ulcers created by EMR healed more rapidly in patients who received preoperative PPI. CONCLUSIONS: The results of the study suggest that preoperative administration of PPI before EMR is useful for controlling and preventing bleeding, and for facilitating the healing of artificial ulcers.

Adenoma↗
PubMed2006

Serum heat shock protein 70 levels and lung cancer risk: a case-control study nested in a large cohort study.

Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (P(trend) = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P(trend) = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (P(trend) = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer.

Adult↗
PubMed2006

TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells.

Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of the TNF family, is a multifunctional cytokine that regulates cell growth, migration, and survival principally through a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14). However, its physiological roles in bone are largely unknown. We herein report various effects of TWEAK on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed Fn14 and produced RANTES (regulated upon activation, healthy T cell expressed and secreted) upon TWEAK stimulation through PI3K-Akt, but not nuclear factor-kappaB (NF-kappaB), pathway. In addition, TWEAK inhibited bone morphogenetic protein (BMP)-2-induced expression of osteoblast differentiation markers such as alkaline phosphatase through mitogen-activated protein kinase (MAPK) Erk pathway. Furthermore, TWEAK upregulated RANKL (receptor activation of NF-kappaB ligand) expression through MAPK Erk pathway in MC3T3-E1 cells. All these effects of TWEAK on MC3T3-E1 cells were abolished by mouse Fn14-Fc chimera. We also found significant TWEAK mRNA or protein expression in osteoblast- and osteoclast-lineage cell lines or the mouse bone tissue, respectively. Finally, we showed that human osteoblasts expressed Fn14 and induced RANTES and RANKL upon TWEAK stimulation. Collectively, TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in MC3T3-E1 cells. TWEAK may thus be a novel cytokine that regulates several aspects of osteoblast function.

3T3 Cells↗
PubMed2006

Relationships of age at menarche and menopause, and reproductive year with mortality from cardiovascular disease in Japanese postmenopausal women: the JACC study.

BACKGROUND: Early menopause is associated with increased risk of coronary heart disease in Caucasian women. However, this association has not been examined in Asian women. METHODS: We conducted a 10-year cohort study of 37,965 Japanese post-menopausal women aged 40-79 years in the Japan Collaborative Cohort (JACC) Study. Causes of death were determined based on the International Classification of Disease. RESULTS: There were 487 mortality of stroke and 178 mortality of coronary heart disease. Late menarche or early menopause, or shorter duration of reproductive period was not associated with risk of mortality from coronary heart disease. However, compared with women with age at menarche < or =13 years, those with age at menarche > or =17 years tended to have increased risk of mortality from stroke: the multivariable hazard ratio was 1.32 (95% confidence interval [CI]: 0.93-1.87, p = 0.10). Compared with women with age at menopause of > or =49 years, those with age at menopause of <49 years tended to have increased risk of coronary heart disease among women aged 40-64 years; the multivariable hazard ratio was 1.85 (95% CI: 0.92-3.73, p = 0.08). CONCLUSIONS: The possible association between early menopause and coronary heart disease among middle-aged women was consistent with the result of observational studies for Caucasian women, and can be explained by a protective effect of endogenous estrogen on the development of atherosclerosis.

Adult↗
PubMed2006

Alcohol consumption and lung cancer mortality in Japanese men: results from Japan collaborative cohort (JACC) study.

BACKGROUND: The relationship between alcohol consumption and increased risk of lung cancer is controversial. This study was set up to investigate the association between alcohol consumption and death from lung cancer in a large Japanese cohort. METHODS: The subjects comprised 28,536 males, aged 40-79 years, living throughout Japan. During 268,464 person-years of follow-up, 377 lung cancer deaths were recorded. The hazard ratio (HR) of alcohol consumption for lung cancer mortality was calculated using the Cox proportional hazards model after adjustment for age, smoking and family history of lung cancer. RESULTS: There was no association between increased mortality from lung cancer and alcohol consumption among current drinkers. Compared with subjects who had never drunk alcohol, the HRs (95% confidence interval [CI]) of death from lung cancer for light (consuming <25.0 g ethanol per day), moderate (25.0-49.9 g per day) and heavy (>or=50 g per day) drinkers were 0.81 (95% CI=0.61-1.07), 0.82 (0.61-1.11) and 0.97 (0.66-1.43), respectively. Further adjustment for fruit and vegetable intake did not change the results, and there was no change in HR materially after excluding those patients who died during the first 5 years of follow-up. CONCLUSIONS: These findings indicate that alcohol consumption was not associated with increased lung cancer mortality in this population of Japanese men.

Adult↗
PubMed2005

Retrospective assessment of influenza vaccine effectiveness among the non-institutionalized elderly population in Japan.

To construct a framework for monitoring the effectiveness of influenza vaccine, we retrospectively surveyed elderly (> or = 65 years old) people living in rural areas of Kyoto prefecture, Japan, using a self-administered questionnaire, for their influenza-related symptoms during the peak influenza season of 2003-2004. A total of 2301 elderly individuals responded, of whom 1533 (66.6%) had been vaccinated. The odds ratio (OR) of vaccination for fever of > or = 38 degrees C, adjusted for sex, age and underlying conditions, was 0.77 (95% confidence interval (CI), 0.40-1.47), and the OR for a diagnosis of influenza in clinics was 0.81 (95% CI, 0.41-1.57). These findings suggested that the vaccine was 20% effective, although this effectiveness was not statistically significant.

Adult↗
PubMed2005

Dietary intake of calcium in relation to mortality from cardiovascular disease: the JACC Study.

BACKGROUND AND PURPOSE: No prospective studies have examined the association between calcium intake and the risk of cardiovascular disease in Japanese populations with a low mean calcium intake. METHODS: Between 1988 and 1990, 110,792 Japanese subjects (46,465 men and 64,327 women) 40 to 79 years of age without a history of stroke, coronary heart disease, or cancer, completed a lifestyle questionnaire including food intake frequency under the Japan Collaborative Cohort (JACC) Study for Evaluation of Cancer Risk Sponsored by Monbusho. By the end of 1999, after 515,029 person years of follow-up, 566 deaths from stroke (101 subarachnoid hemorrhages, 140 intraparenchymal hemorrhages, and 273 ischemic strokes) and 234 deaths from coronary heart disease had been documented. RESULTS: The intake of total calcium tended to be inversely associated with mortality from total stroke but not from coronary heart disease or total cardiovascular disease for men and women. The inverse association with dairy calcium intake was apparent for total stroke, both hemorrhagic and ischemic. The multivariate relative risk for men with highest versus lowest quintiles of dairy calcium intake was 0.53 (95% CI, 0.34 to 0.81) for total stroke, 0.46 (0.23 to 0.91) for hemorrhagic stroke, and 0.53 (0.29 to 0.99) for ischemic stroke; corresponding relative risks for women were 0.57 (0.38 to 0.86), 0.51 (0.28 to 0.94), and 0.50 (0.27 to 0.95). CONCLUSIONS: Dietary calcium intake from dairy products was associated with reduced mortality from stroke for Japanese men and women.

Adult↗
PubMed2005

Autonomic nervous evaluation in the early stages of olivopontocerebellar atrophy.

The clinical significance of evaluating autonomic nervous system functions in the early stages of olivopontocerebellar atrophy (OPCA) has been investigated in 13 OPCA out-patients (7 males and 6 females, mean age: 51.0 years). We have employed measurements of blood pressure, plasma norepinephrine (NE), CVR-R, low-frequency power/high-frequency power ratio (L/H), high-frequency power (HF) score and heart rate (HR) monitoring using Holter ECG recording for evaluation of CVR-R. We have also carried out urodynamic examinations, focusing on the possible existence of bladder dysfunction. Although no significant changes were noted between control and OPCA groups concerning HR, CVR-R, L/H, plasma levels of norepinephrine and systolic blood pressure, HF (high-frequency power) (ms(2)), especially at night time, invariably showed a significant decline in OPCA groups. All OPCA patients who showed a decreased circadian HF also exhibited a tendency towards urinary bladder dysfunction. The present results appear to relate to disorder of the parasympathetic autonomic nervous system and neuromuscular dysfunction in the lower urinary tract. In conclusion, HRV (heart rate variability) analysis is a useful and safe tool and a keen predictor for evaluating functional states of autonomic nervous activity, especially in the early stages of OPCA. This study has also suggested the possible efficacy of urodynamic measurements in OPCA patients as an indicator of neuromuscular dysfunction in the lower urinary tract and of parasympathetic malfunction.

Adult↗
PubMed2005

Walking and sports participation and mortality from coronary heart disease and stroke.

OBJECTIVES: We aimed to examine the impact of exercise on mortality from cardiovascular disease (CVD) in Asian populations. BACKGROUND: Few data have been available in Asian countries, where job-related physical activity is higher than that in Western countries. METHODS: Between 1988 and 1990, 31,023 men and 42,242 women in Japan, ages 40 to 79 years with no history of stroke, coronary heart disease (CHD), or cancer, completed a self-administered questionnaire. Systematic mortality surveillance was performed through 1999, and 1,946 cardiovascular deaths were identified. We chose the second lowest categories of walking and sports participation as the reference to reduce a potential effect of ill health. RESULTS: Men and women who reported having physical activity in the highest category (i.e., walking > or =1 h/day or doing sports > or =5 h/week) had a 20% to 60% lower age-adjusted risk of mortality from CVD, compared with those in the second lowest physical activity category (i.e., walking 0.5 h/day, or sports participation for 1 to 2 h/week). Adjustment for known risk factors, exclusion of individuals who died within two years of baseline inquiry, or gender-specific analysis did not substantially alter these associations. The multivariate-adjusted hazard ratios (95% confidence interval) for the highest versus the second lowest categories of walking or sports participation were 0.71 (0.54 to 0.94) and 0.80 (0.48 to 1.31), respectively, for ischemic stroke (IS); 0.84 (0.64 to 1.09) and 0.51 (0.32 to 0.82), respectively, for CHD; and 0.84 (0.75 to 0.95) and 0.73 (0.60 to 0.90), respectively, for CVD. CONCLUSIONS: Physical activity through walking and sports participation might reduce the risk of mortality from IS and CHD.

Adult↗