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Biomedical subjects

Ken Takahashi

Publications and source records attributed to Ken Takahashi.

At least 19 recordsLinked to original sources

Inequality in the health status of workers in small-scale enterprises.

BACKGROUND: Small-scale enterprises (SSEs) usually share poorer resources for promoting occupational health. AIM: To investigate inequality of health status among SSEs in Japan. METHOD: A cross-sectional, multiple-centred study was carried out using the periodical health check-up data for the fiscal year 2000 to compare the age-adjusted proportions of workers with hypertension (HT), hyperlipidaemia, impaired glucose tolerance (IGT) and obesity and of current smokers by size of enterprise, i.e. or=1000 employees in Japan. RESULTS: From five leading occupational health organizations, data were collected for 9833 enterprises with a total of 436 729 subjects, 302 383 males and 134 346 females. The proportions of workers in SSEs with or=50 male employees. The prevalence of smokers in SSEs with or=50 male employees. These proportions showed a significantly increasing tendency with decreasing size of male workforce. CONCLUSION: Despite the cross-sectional design and only adjusting age as a potential confounder, higher proportions of HT, IGT, obesity and smoking in male workers were found in SSEs compared to larger organizations.

Adult↗

A retrospective cohort study among iron-steel workers in Anshan, China: exposure assessment.

Although adequate assessment of exposure is needed in epidemiological studies among foundry workers, previous studies are often lacking in this aspect. We conducted a retrospective cohort study of a Chinese iron and steel company with a 14-yr follow up during 1980-1993. Exposure assessment was performed for a single job, i.e., the current job for the active worker and the longest job for the retired or deceased worker as of the end of the follow-up, which was allocated as the surrogate of lifetime job and was applied to a job-exposure matrix. Of the 147,062 cohort members, 52,394 males (43%) and 5,291 females (21%) were exposed to any of 15 hazardous factors such as dust, silica, PAHs (polycyclic aromatic hydrocarbons), CO (carbon monoxide) and heat. In 2,104 randomly selected samples, the exposure assessment of exposed workers based on a single job was found to be 12-14% lower than the real situation. This study suggests that the exposure assessment is valuable in evaluating the health effects among the foundry workers, despite some limitations such as underestimation of exposure assessment and the lack of data regarding smoking and drinking habits.

China↗

Quantitative detection of p53 mutations in plasma DNA from tobacco smokers.

In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke.

Baltimore↗

Essential role of IPS-1 in innate immune responses against RNA viruses.

IFN-beta promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1-deficient mice showed severe defects in both RIG-I- and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus-induced interferon regulatory factor-3 and nuclear factor kappaB activation was also impaired in IPS-1-deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

Adaptor Proteins, Signal Transducing↗

Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA.

Upon viral infection, host cells trigger antiviral immune responses by inducing type I IFN and inflammatory cytokines. dsRNA generated during viral replication is recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, which interact with an adaptor, IFN-beta promoter stimulator-1, to activate the transcription factors NF-kappaB and IFN regulatory factor 3. In this article we demonstrate that caspase-8 and caspase-10 are involved in these pathways. Both caspases were cleaved during dsRNA stimulation, and overexpression of a cleaved form of these caspases activated NF-kappaB. Knockdown of caspase-10 or caspase-8 in a human cell line resulted in the reduction of inflammatory cytokine production. Cells derived from caspase-8-deficient mice also showed reduced expression of inflammatory cytokines as well as NF-kappaB activation. Furthermore, the Fas-associated death domain protein interacted with these two caspases and IFN-beta promoter stimulator 1. These results indicate that caspase-8 and caspase-10 are essential components that mediate NF-kappaB-dependent inflammatory responses in antiviral signaling.

Adaptor Proteins, Signal Transducing↗

The development and regulation of occupational exposure limits in Japan.

The Ministry of Health, Labor and Welfare, on an administrative basis, establishes and supervises the Administrative Concentration Level, which can be viewed as an Occupational Exposure Limit (OEL) legally binding employers to maintain a good working environment. The Japan Society for Occupational Health, on a scientific basis, establishes the Recommended OELs, which can be viewed as a reference value for preventing adverse health effects on individual workers. In the case of carcinogens, Reference Values are recommended instead of OELs, corresponding to lifetime excessive risk of 10(-3) and 10(-4). The former is based on monitoring of the ambient working environment (area monitoring) while the latter is based on the monitoring of the individual worker. The two OELs influence each other in the course of establishment.

Government Regulation↗

Estimation of future mortality from pleural malignant mesothelioma in Japan based on an age-cohort model.

BACKGROUND: Japanese consumption of asbestos increased rapidly after the 1950s and lingered at a high level while the world's consumption decreased substantially after the 1980s. Mesothelioma is due primarily to asbestos, and the number of deaths in Japan is expected to increase in the future. METHOD: We estimated the future number of pleural mesothelioma deaths among males in Japan using an age-cohort model. RESULTS: Analyses showed that there would be about 100,000 deaths in Japan due to pleural mesothelioma in the next 40 years. Compared with the statistics in European countries, the ratio of expected death numbers to the population size is remarkably close to linear. The data-point for Japan was slightly lower than that which could be expected from the linear relationship. CONCLUSIONS: The limited availability of data may result in underestimation. Taking into consideration the consumption pattern of asbestos in recent decades, the incorporation of later cohorts will improve the estimation.

Adult↗

Substantial differences in preparedness for emergency infection control measures among major hospitals in Japan: lessons from SARS.

Emergency infection control measures are essential in hospitals. Although Japan was spared from the 2003 epidemic of severe acute respiratory syndrome (SARS), hospitals were placed on high alert. The actual preparedness level of hospitals can be determined by examining individual perceptions among the hospital healthcare workers (HCWs). The objective of this study was to assess the level of preparedness of emergency infection control measures in Japan and to quantify the differences in preparedness across institutions and disciplines. From July to September 2003, a questionnaire survey concerning the perceptions of risks and countermeasures and knowledge about SARS was distributed at seven tertiary hospitals. Disciplines were categorized as emergency room (ER)/intensive care unit (ICU), surgical, medical, and "others". Of the 9978 questionnaires administered, 6929 valid responses were received and analyzed. After adjusting for age, sex, and job category, specific institutional measures (I-scores) were found to be more indicative of the level of preparedness across institutions and disciplines than were measures of overall effectiveness (E-scores) or knowledge of preventive measures (K-scores). In particular, the difference in I-scores was much more substantial across institutions than across disciplines. Across disciplines, surgical ranked lower than ER/ICU or medical. In conclusion, substantial differences in emergency infection control measures, as perceived by HCWs, exists among hospitals in Japan, with the differences across institutions exceeding those across disciplines. To achieve a higher level of preparedness for infectious diseases, institutions should designate and implement effective emergency infection control measures.

Disaster Planning↗

Cystic beta2-microglobulin amyloidoma in a patient on long-term hemodialysis.

We report a patient with beta2 microglobulin amyloidosis (beta2M) in whom cystic tumors were seen in the bilateral axillary region. The patient was a 68-year-old woman who had been on hemodialysis for more than 20 years because of IgA nephropathy. Computed tomography-guided biopsy was performed to confirm the diagnosis. Congo red staining, beta2M immunohistochemistry, and electron microscopy examination of the biopsied sample showed extended beta2M deposits in the cystic tumor. beta2M-related amyloidosis in patients with long-term dialysis commonly presents as osteoarticular disease, although a soft-tissue pseudotumor, known as amyloidoma, has been reported. This is the first report in the English-language literature of amyloidosis presenting as bilateral axillary cystic tumors.

Aged↗

Three-dimensional echocardiography improves the understanding of the mechanisms and site of left atrioventricular valve regurgitation in atrioventricular septal defect.

OBJECTIVES: The purpose of this study was to determine whether 3-dimensional echocardiography (3DE) provides additional information regarding the mechanisms and sites of left atrioventricular valve regurgitation in atrioventricular septal defect compared with transesophageal 2-dimensional echocardiography (2DE). METHODS: Eleven patients with a median age of 5.4 years (2.9-11.6 years) and a median weight of 16.8 kg (13.7-38.3 kg) with an atrioventricular septal defect underwent simultaneous transesophageal 2DE and 3DE before operation. RESULTS: The 2DE-3DE agreement for the assessment of the superior and mural leaflet size was 72.7%. The 2DE-3DE agreement for coaptation failure, a residual or primary cleft, and commissural abnormalities as a mechanism of regurgitation were 72.7%, 63.6%, and 36.4%, respectively. For jet sites the 2DE-3DE agreement was 63.6% for a commissural and central location. CONCLUSION: Three-dimensional echocardiography provides new and superior data regarding the mechanisms and sites of left atrioventricular valve regurgitation in atrioventricular septal defect.

Cardiac Surgical Procedures↗

Recent trends in ILO conventions related to occupational safety and health.

The present study was conducted to analyze the ratification status of International Labour Organization (ILO) conventions related to occupational safety and health (OSH) by ILO member states in terms of national indicators (length of ILO membership and national income status) and regional affiliation. 17 conventions designated as OSH-related by the 2003 International Labour Conference were examined. In general, countries with longer ILO membership ratified higher numbers of conventions related to OSH. With some variation, long-membership countries had the largest number of ratifications, followed by middle- and short-membership countries in all regions. There were also incremental increases in the number of ratifications for OSH-related conventions according to the national income status. Common regional characteristics that could not be explained by the factors studied also existed. Future efforts to increase ratification at an international level will need to consider the factors influencing ratification practice among the member states.

Congresses as Topic↗

Cyclo-oxygenase-2 over-expression is associated with human esophageal squamous cell carcinoma.

Cyclo-oxygenase (COX)-2 is not usually detectable in normal tissues but is induced in inflammation and carcinogenesis. The level of COX-2 is elevated in cancer tissues of the colon, bladder, and skin. In the esophagus, squamous cell carcinoma and adenocarcinoma are known to express COX-2. The purpose of this study was to clarify the association of COX-2 expression with clinicopathological factors of squamous cell carcinoma. The immunohistochemical expression of COX-2 was examined in 48 surgical specimens of esophageal squamous cell carcinoma. Although COX-2 over-expression was more frequently observed in tumors invading the submucosa (T1b, 76.4%), muscularis propria (T2, 57.1%), adventitia, or adjacent organs (T3 approximately 4, 83.3%), even 33.3% of mucosal cancers, such as T1a, showed COX-2 over-expression. COX-2 over-expression was present in 82.3% of lymph node-negative patients but in only 54.8% of lymph node positive patients. There was no difference in COX-2 over-expression between the earlier stages (0 and I, 60%) and more advanced stages (II approximately IV, 69.6%). COX-2 over-expression did not correlate with survival during 3 years of follow-up. These findings suggest that COX-2 is associated with the phenotype of the esophageal squamous cell carcinoma cells, including superficial cancer cells, and may be related to tumor growth in esophageal squamous cell carcinoma.

Aged↗

Computed tomography-guided mediastinal drainage for iatrogenic perforation of the esophagus.

We report a case of perforation of the esophagus associated with mediastinitis and pneumomediastinum during endoscopic treatment. The patient was successfully treated by means of nonsurgical computed tomography-guided mediastinal drainage. Esophagoscopy demonstrated a scar on the 14th day at the perforation site. This nonsurgical treatment with computed tomography-guided mediastinal drainage is proposed as a less invasive treatment for iatrogenic perforation of the esophagus.

Aged↗

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

BACKGROUND: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. OBJECTIVE: Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. METHODS: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. RESULTS: Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). CONCLUSION: We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

Adult↗

Association of psychological well-being with oral conditions in Japanese workers.

Although the effect of disorders on psychological well-being is well-known, there are few studies focusing on oral conditions at the worksite. The present study examined the association between psychological well-being and oral conditions of Japanese workers. A cross-sectional study was performed using data from 1381 Japanese civil service officers aged 20-59 yr old. Psychological well-being was measured with the 12-item version of the General Health Questionnaire (GHQ-12) in a comprehensive health questionnaire, while measures for oral condition included self-rated oral health, oral symptoms and clinical indicators: dental caries, periodontal status and number of missing teeth. The mean GHQ scores according to the levels of each oral condition were estimated by analysis of variance, separately for males and females. Higher scores corresponded to poorer psychological well-being. Age, gender, smoking and type of occupation were adjusted in a multivariate analysis. Psychological well-being was not associated significantly with dental caries, periodontal status or number of missing teeth. The adjusted means of the GHQ scores for ;conscious of appearance of mouth' were significantly different among the categories for both genders (male: p<0.001, female: p=0.018). For five of six oral symptoms, the adjusted means of GHQ scores were lowest for those respondents who rated their oral symptoms as ;never or hardly ever.' Our results did not show that psychological well-being was associated with oral conditions measured by clinical indicators. However, an association was found between some oral symptoms and psychological well-being. Absence of oral symptoms seems to be related to better psychological well-being.

Adult↗

[Long working hours and cardiovascular diseases: a systematic review].

Three years have passed since the countermeasures against the adverse health effects of overwork started in Japan, and fruitful outcomes have been expected. In the current study, a systematic review of articles was performed regarding the association of long working hours (LWH) with cardiovascular diseases (CVD) to obtain recent evidence of their association. An electronic database search was conducted using PubMed among English-written original articles published until December, 2004. A total of twelve articles were found conforming to the study's inclusion criteria, but evidence supporting the association of LWH and CVD was not detected. However, some distinctive studies related to the prevention of CVD were found relating to the concept of sensitive psychosocial factors such as vital exhaustion, and to the statistical modeling of occupational factors and biological indicators with the interaction term of psychosocial factors. Further studies will be needed to clarify the association of LWH and CVD.

Adult↗

A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA.

The innate immune system recognizes nucleic acids during infection or tissue damage; however, the mechanisms of intracellular recognition of DNA have not been fully elucidated. Here we show that intracellular administration of double-stranded B-form DNA (B-DNA) triggered antiviral responses including production of type I interferons and chemokines independently of Toll-like receptors or the helicase RIG-I. B-DNA activated transcription factor IRF3 and the promoter of the gene encoding interferon-beta through a signaling pathway that required the kinases TBK1 and IKKi, whereas there was substantial activation of transcription factor NF-kappaB independent of both TBK and IKKi. IPS-1, an adaptor molecule linking RIG-I and TBK1, was involved in B-DNA-induced activation of interferon-beta and NF-kappaB. B-DNA signaling by this pathway conferred resistance to viral infection in a way dependent on both TBK1 and IKKi. These results suggest that both TBK1 and IKKi are required for innate immune activation by B-DNA, which might be important in antiviral innate immunity and other DNA-associated immune disorders.

Adaptor Proteins, Signal Transducing↗

IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction.

Type I interferons are central mediators for antiviral responses. Using high-throughput functional screening of interferon inducers, we have identified here a molecule we call interferon-beta promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-kappaB transcription factors. TBK1 and IKKi protein kinases were required for the IPS-1-mediated interferon induction. IPS-1 contained an N-terminal CARD-like structure that mediated interaction with the CARD of RIG-I and Mda5, which are cytoplasmic RNA helicases that sense viral infection. 'Knockdown' of IPS-1 by small interfering RNA blocked interferon induction by virus infection. Thus, IPS-1 is an adaptor involved in RIG-I- and Mda5-mediated antiviral immune responses.

Adaptor Proteins, Signal Transducing↗