Kanagawa Health Service Association

Yokohama-shi, Japan

Kanagawa Health Service Association

Yokohama-shi, Japan
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Ishihara N.,Kanagawa Health Service Association
Nihon eiseigaku zasshi. Japanese journal of hygiene | Year: 2016

Immediately after the official recognition of Minamata disease (1956.5.l) a study group at Kumamoto University suggested that Minamata disease was caused by food poisoning. The next year, this suggestion was accepted by the Ministry of Health and Welfare (MHW). Prior to the decision to apply the Food Sanitation Act (FSA), the local government asked MHW for the application of FSA. Soon after, the chief of the Public Health Bureau replied to the local government that the application of FSA to the Minamata area was impossible. Epidemiological investigations of residents and polluted areas, therefore, were not carried out. Data essential for the screening for exposed residents were unavailable. The criteria for the screening were presented. The Environmental Agency (EA) presented the criteria in the form of notice in 1971, which were revised in 1977. Notwithstanding the clear difference between the original and revised criteria, EA insisted that these two sets of criteria were quite similar. This insistence by EA and the absence of epidemiological data on residents and polluted area resulted in the present confusion about Minamata disease. The application of FSA was stopped by bureaucrats who had no interest in the environmental problems and by several scientists patronized by stakeholders (Chisso, Japanese Association of Chemical Industries, MHW and EA). Stakeholders suppressed science.


Shingyoji M.,Chiba Cancer Center | Iizasa T.,Chiba Cancer Center | Higashiyama M.,Japan National Cardiovascular Center Research Institute | Imamura F.,Japan National Cardiovascular Center Research Institute | And 8 more authors.
BMC Cancer | Year: 2013

Background: We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples.Methods: Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS).Results: High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers.Conclusions: These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer. © 2013 Shingyoji et al; licensee BioMed Central Ltd.


Kuramoto H.,Kanagawa Health Service Association | Iwami Y.,Cytology Center | Sugimoto N.,Cytology Center | Kato C.,Cytology Center | And 2 more authors.
Acta Cytologica | Year: 2012

Objective: To evaluate the usefulness of a new liquid-based cytological procedure in a population screening program for cervix cancer. Subjects and Methods: Subjects were 1,000 women who underwent primary screening at the Kanagawa Health Service Association. The cytological specimens obtained by either cotton stick and Cytobrush® or Cervex-Brush® were processed using the Thinlayer Advanced Cytology Assay System (TACAS™), following the manufacturer's instructions. Results: (1) Cells were evenly distributed on specimens and stained evenly; (2) shrinkage of cells was 5% based on measurement of the nuclear diameters of granulocytes in comparison with those of the conventional procedure; (3) incidences of cells that occupied the whole area, 1/20≤, 1/4≤, 1/4> of the observation fields were 58.8, 26.2, 12.0 and 3.0%, respectively; (4) number of the squamous cells in cases with 1/4> was <5,000, in which specimen cells were correctly obtained from the squamocolumnar junction except in 3 cases (0.3%); (5) bleeding at cellular sampling was 5%, but did not disturb cell analysis; (6) inflammation caused by organisms was easily diagnosed; (7) detection rate of abnormal cytology was 4.3%, including ASC-US in 2.8% and ASC-H in 0.1%. Conclusion: TACAS is a feasible and useful cytological procedure. © 2012 S. Karger AG, Basel.


Ishihara N.,Kanagawa Health Service Association
Nihon eiseigaku zasshi. Japanese journal of hygiene | Year: 2014

The first reports of methylmercury intoxication appeared in 1865 and 1866. These reports had sensational effects in European countries, and were introduced not only in journals but also in newspapers. These two reports were referable in Japan at the latest in 1927. The formation of organic mercury in the production of acetoaldehyde was also referable in 1906 in Japan. In 1931 (one year before the start of acetoaldehyde production in Minamata) these important reports cited above were referable in Kumamoto University, and there were warnings about the toxicity of organic mercury and environmental pollution prior to the start of acetoaldehyde production. However, not only the plant, authorities (Ministry of Welfare), and Kumamoto Prefectural Office, but also the scientists completely ignored these reports. Waste was dumped into the environment without any treatment. Serious pollution of the environment by organic mercury started, which resulted in the outbreak of Minamata disease (=methylmercury intoxication).


Nishioka M.,Comfort Medical Foundation | Imaizumi A.,Ajinomoto Co. | Ando T.,Ajinomoto Co. | Tochikubo O.,Kanagawa Health Service Association
PLoS ONE | Year: 2013

The plasma free amino acid (PFAA) profile is affected by various nutritional conditions, such as the dietary energy balance. Regarding the clinical use of PFAA profiling, it is of concern that differences in food ingestion patterns may generate systematic errors in a plasma amino acid profile and constitute a confounding factor in assessment. In this study, the overnight impact of the dietary energy balance on the postprandial plasma amino acid profile was investigated to elucidate in particular the effects of high protein meals typical in Japanese cuisine. We conducted diet-controlled, crossover trials in eleven healthy male volunteers aged 40-61 y. They consumed either a normal meal (meal N) or high protein meal (meal H) at dinner. Forearm venous blood was collected, and plasma amino acid concentrations were measured before dinner and the next morning. We found that a high protein meal in the evening that contained 40% energy would significantly increase the PFAA concentration the next morning, even more than 12 hours after the meal. Among amino acids, the most significant difference was observed in the branched-chain amino acids (BCAAs) and in some urea-cycle related compounds. If the subject consumed the high protein diet at dinner, the PFAA profile after overnight fasting might be still affected by the meal even 12 hours after the meal, suggesting that the PFAA profile does not reflect the subject's health condition, but rather the acute effect of high protein ingestion. © 2013 Nishioka et al.


Fukuda T.,University of Tokyo | Oda K.,University of Tokyo | Wada-Hiraike O.,University of Tokyo | Sone K.,University of Tokyo | And 11 more authors.
Gynecologic Oncology | Year: 2015

Objective The anti-malarial drug chloroquine (CQ) is also known as an autophagy inhibitor. Autophagy can promote tumor growth by fueling the necessary energy metabolism and inducing resistance to chemotherapy and/or irradiation in various human cancers. However, the role of autophagy in endometrial cancer has not yet been established. We investigated the anti-tumor effects and autophagy inhibition caused by CQ in endometrial cancer cells. Methods Cell proliferation and cell cycle were assessed in response to CQ in six endometrial cancer cell lines by using an MTT assay and/or flow cytometry. To assess the level of autophagy, western blotting and an immunofluorescence assay were used to measure LC3 expression. The effects of knockdown of either ATG5 or ATG7, both of which are indispensable for induction of autophagy, were assessed via an MTT assay. Sensitivity to CQ was compared between parental and cisplatin-resistant (CP-r) Ishikawa endometrial cancer cells. Results CQ suppressed proliferation in all six endometrial cancer cell lines in a dose-dependent manner, whereas it increased the population of apoptotic cells. Inhibition of autophagy via knockdown of either ATG5 or ATG7 decreased the sensitivity to CQ. Additionally, sensitivity to cisplatin was improved by knocking down ATG5 or ATG7. Finally, CP-r Ishikawa cells, with a high basal level of autophagy, were more sensitive to CQ than parental Ishikawa cells. Conclusions Our data suggest that autophagy is involved in endometrial tumor growth and cisplatin resistance. Furthermore, our data support a therapeutic role for CQ in endometrial cancer cells with upregulation of autophagy. © 2015 Elsevier Inc. All rights reserved.


PubMed | Kanagawa Health Service Association
Type: Journal Article | Journal: Nihon eiseigaku zasshi. Japanese journal of hygiene | Year: 2016

Immediately after the official recognition of Minamata disease (1956.5.l) a study group at Kumamoto University suggested that Minamata disease was caused by food poisoning. The next year, this suggestion was accepted by the Ministry of Health and Welfare (MHW). Prior to the decision to apply the Food Sanitation Act (FSA), the local government asked MHW for the application of FSA. Soon after, the chief of the Public Health Bureau replied to the local government that the application of FSA to the Minamata area was impossible. Epidemiological investigations of residents and polluted areas, therefore, were not carried out. Data essential for the screening for exposed residents were unavailable. The criteria for the screening were presented. The Environmental Agency (EA) presented the criteria in the form of notice in 1971, which were revised in 1977. Notwithstanding the clear difference between the original and revised criteria, EA insisted that these two sets of criteria were quite similar. This insistence by EA and the absence of epidemiological data on residents and polluted area resulted in the present confusion about Minamata disease. The application of FSA was stopped by bureaucrats who had no interest in the environmental problems and by several scientists patronized by stakeholders (Chisso, Japanese Association of Chemical Industries, MHW and EA). Stakeholders suppressed science.


PubMed | Kanagawa Health Service Association, National Center for Global Health and Medicine and University of Tokyo
Type: Journal Article | Journal: Gynecologic oncology | Year: 2015

Radiation therapy is a key therapeutic strategy for endometrial carcinomas. However, biomarkers that predict radiosensitivity and drugs to enhance this sensitivity have not yet been established. We aimed to investigate the roles of TP53 and MAPK/PI3K pathways in endometrial carcinomas and to identify appropriate radiosensitizing therapeutics. D10 values (the irradiating dose required to reduce a cell population by 90%) were determined in eight endometrial cancer cell lines with known mutational statuses for TP53, PIK3CA, and KRAS. Cells were exposed to ionizing radiation (2-6Gy) and either a dual PI3K/mTOR inhibitor (NVP-BEZ235) or a MEK inhibitor (UO126), and their radiosensitizing effects were evaluated using clonogenic assays. The effects of silencing hypoxia-inducible factor-1 (HIF-1) expression with small interfering RNAs (siRNAs) were evaluated following exposure to ionizing radiation (2-3Gy). D10 values ranged from 2.0 to 3.1Gy in three cell lines expressing wild-type TP53 or from 3.3 to more than 6.0Gy in five cell lines expressing mutant TP53. NVP-BEZ235, but not UO126, significantly improved radiosensitivity through the suppression of HIF-1/vascular endothelial growth factor-A expression. HIF-1 silencing significantly increased the induction of the sub-G1 population by ionizing radiation. Our study data suggest that TP53 mutation and PI3K pathway activation enhances radioresistance in endometrial carcinomas and that targeting the PI3K/mTOR or HIF-1 pathways could improve radiosensitivity.


PubMed | Kanagawa Health Service Association
Type: Comparative Study | Journal: Acta cytologica | Year: 2015

To evaluate a fully automated processing system (TACAS Pro) for liquid-based procedures (LBPs).Materials were 3,483 and additionally 502 specimens that were taken at Kanagawa Health Service Association. Specimens obtained with a Cervex-Brush were first smeared to glass slides using one side of the brush and then processed to TACAS Pro.(1) The microscopy watching time per normal case was 3.65 0.85 min in the conventional procedure, whereas in the LBP it was 1.95 0.60 min, and the latter reduced workload to 53%. (2) The handling time of TACAS Pro per day was 2 h and 25.8 min. The workload at a laboratory offset it and revealed the work saving to be 63.8%. (3) Unsatisfactory rates were 0% in the conventional procedure, whereas in the LBP it was 1.88% at first. The latter rate decreased to 0.5% after system improvement. (4) Specimens which may disturb microscopy analysis were found in 1.06%, including 3 cases of possible carry-over of cells to the following slides. An additional study with the revised system confirmed no carry-over. (5) Incidences of abnormal cytology were consistent between the two methods.The revised automated processing system TACAS Pro is a feasible and useful LBP and reduces the workload of cytology laboratories.


PubMed | Kanagawa Health Service Association, National Center for Global Health and Medicine and University of Tokyo
Type: Journal Article | Journal: Gynecologic oncology | Year: 2016

Survivin is an anti-apoptotic protein encoded by the baculoviral inhibitor of apoptosis repeat-containing (BIRC5) gene and is upregulated in 83% of endometrial cancers. We aimed to elucidate the prognostic importance of BIRC5 expression, and evaluate survivin as a therapeutic target for endometrial cancer, by knock-down of BIRC5 and using the survivin inhibitor-YM155.RNA sequencing data in 234 patients with endometrial carcinoma was obtained from The Cancer Genome Atlas database, and analyzed using Kaplan-Meier method, log-rank test and Cox proportional hazard model. Expressions of survivin in 16 endometrial cancer cell lines were analyzed by western blotting. Knocking down effect on survivin expression was evaluated using a small interfering RNA (siRNA). The anti-proliferative and pro-apoptotic effects of YM155 were assessed with cell viability, flow cytometry, and annexin V/propidium iodide assays.High expression of BIRC5 was associated with poor progression free survival (P=0.006), and shown to be an independent prognostic factor (HR=1.97, 95% CI=1.29-4.5, P=0.045). Survivin was upregulated in 14 of 16 (87.5%) endometrial cancer cell lines, compared with endometrial immortalized cells. Apoptosis was induced by knockdown of BIRC5 in all 3 cell lines examined. YM155 showed increased population of sub-G1 cells (P<0.001) in all 16 cell lines, and IC50 values to YM155 were <50nm in 15 cell lines. YM155 dose-dependently and significantly increased the apoptotic cell population in all 16 cell lines (P<0.001).Present study indicated that survivin expression is a significant prognostic factor and that survivin is a promising therapeutic target for endometrial cancer.

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