Publications by authors named "Hisayoshi Kondo"

78 Publications

53BP1 expression as a biomarker to differentiate thyroid follicular tumors.

Endocr Connect 2021 Mar;10(3):309-315

Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

We have previously reported that the expression of p53-binding protein 1 (53BP1) in nuclear foci (NF), a marker reflecting DNA damage response (DDR), detected using immunofluorescence (IF) is useful to estimate the malignant potency of diverse cancers. In this prospective study, we clarified the impact of 53BP1 expression via IF as a biomarker to differentiate thyroid follicular tumors (FTs) with liquid-based cytology (LBC). A total of 183 consecutively obtained-LBC samples, which were preoperatively suspected as FTs, were analyzed. Before histological diagnosis, the type of 53BP1 immunoreactivity in LBC was classified as follows: low DDR type, one or two NF; high DDR type, three or more NF; large foci type, larger than 1.0 μm; abnormal type, intense nuclear staining. Among the 183 cases, 136 cases were postoperatively diagnosed as FTs, including adenomatous goiter (AG, n = 30), follicular adenoma (FA, n = 60), FT-uncertain malignant potency (FT-UMP, n = 18), and follicular carcinoma (FC, n = 28), and 47 cases were diagnosed as tumors other than FTs or technically inadequate materials. Total 136 FT cases were collated with the type of 53BP1 immunoreactivity in LBC. The mean incidence expressing abnormal 53BP1 expression was significantly higher in FC than FA (9.5% vs 2.6%, P-value < 0.001). When adopting 4.3% as a cut-off value to distinguish FC from FA, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.3, 83.3, 71.4, and 94.3%, respectively. Therefore, IF analysis of 53BP1 expression can be employed as a novel technique to diagnose FTs and to distinguish between different types of FTs using LBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-20-0630DOI Listing
March 2021

The Contribution of Genetic Variants to the Risk of Papillary Thyroid Carcinoma in the Kazakh Population: Study of Common Single Nucleotide Polymorphisms and Their Clinicopathological Correlations.

Front Endocrinol (Lausanne) 2020 22;11:543500. Epub 2021 Jan 22.

Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Objective: Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities. We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on PTC risk and to evaluate clinicopathological correlations of these genetic variants in the Kazakh population for the first time.

Methods: Eight SNPs were genotyped in 485 patients with PTC and 1,008 healthy control Kazakh subjects. The association analysis and multivariable modeling of PTC risk by the genetic factors, supplemented with rigorous statistical validation, were performed.

Result: Five of the eight SNPs: rs965513 (/, = 1.3E-16), rs1867277 ( 5'UTR, = 7.5E-06), rs2439302 ( intron 1, = 4.0E-05), rs944289 (/, = 4.5E-06) and rs10136427 ( upstream = 9.8E-03) were significantly associated with PTC. rs966423 (, = 0.07) showed a suggestive association. rs7267944 () was associated with PTC risk in males ( = 0.02), rs1867277 () conferred the higher risk in subjects older than 55 years ( = 7.0E-05), and rs6983267 () was associated with pT3-T4 tumors ( = 0.01). The contribution of genetic component (unidirectional independent effects of rs965513, rs944289, rs2439302 and rs10136427 adjusted for age and sex) to PTC risk in the analyzed series was estimated to be 30-40%.

Conclusion: Genetic factors analyzed in the present work display significant association signals with PTC either on the whole group analysis or in particular clinicopathological groups and account for about one-third of the risk for PTC in the Kazakh population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.543500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862756PMC
January 2021

Use of vonoprazan for management of systemic sclerosis-related gastroesophageal reflux disease.

Biomed Rep 2021 Feb 17;14(2):25. Epub 2020 Dec 17.

Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan.

Gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) can significantly reduce a patient's quality of life. GERD in SSc is occasionally resistant to conventional anti-acid treatment. Vonoprazan is an H/K-ATPase blocker that is approved in Japan for treatment of GERD. The aim of the present study was to evaluate the efficacy of vonoprazan in SSc-related GERD. The frequency scale for symptoms of GERD (FSSG) scores were collected before and after vonoprazan treatment in 15 SSc patients with GERD. Additionally, endoscopic esophagogastroduodenoscopy was performed in select patients. Conventional proton pump inhibitors or histamine-2 receptor antagonists had been previously administered in 93% (14/15) of the patients. Although the baseline esophagogastroduodenoscopy examination did not show severe erosion in the majority of patients, the mean total FSSG score before vonoprazan treatment was notably high (25.2±10.7) compared to a normal score of <8. After vonoprazan treatment, the FSSG score decreased to 9.6±7.0. The mean improvement rate of the total FSSG, acid reflux and dysmotility scores were 60.8±21.2% (P=0.0004), 67.3±24.8% (P<0.0001) and 55.4±26.0% (P=0.0022), respectively. These results suggest that vonoprazan may be a potentially effective treatment for GERD in patients with SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/br.2020.1401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780750PMC
February 2021

Japan DMAT operations in the Diamond Princess cruise ship: COVID-19 medical operation.

Am J Disaster Med 2020 Summer;15(3):207-218

Vice-President, Fujisawa City Hospital, Fujisawa, Kanagawa, Japan.

Objective: The aim of this study was to identify positive effects from the Japan Disaster Medical Assistant Team (DMAT) medical operation in the Diamond Princess cruise ship (DP).

Methods: Japan DMAT dispatched and managed the medical operation for DP passengers and crew members. The records of communication logs for the DMAT were evaluated.

Results: 472 DMAT members were responded. DMAT took 3 to 4 days to manage patients due to a lack of medical supplies at the early phase of operation. The prescription was delayed for prescription required passengers that include passengers who will be in critical health conditions without prescriptions. DMAT conducted a strategic operation and developed categorization for medical care and patient transport. Eventually, DMAT constructed flow to provide rapid medical care and prescription distributions for passengers and crew members.

Conclusion: DMAT has been required to respond to unforeseen disasters in the framework since the Fukushima Nuclear Plant accident in 2011. All the past several types of disaster response were contributed to managing medical operations at the DP. These operations are thought to reduce preventable deaths from Coronavirus disease 2019 (COVID-19).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5055/ajdm.2020.0369DOI Listing
December 2020

Intention to Return and Perception of the Health Risk Due to Radiation Exposure Among Residents in Tomioka Town, Fukushima Prefecture, Stratified by Gender and Generation.

Disaster Med Public Health Prep 2020 Dec 1:1-8. Epub 2020 Dec 1.

Department of Global Health, Medicine and Welfare, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Objective: The aim of this study was to clarify residents' intentions to return (ITR) to Tomioka town, Fukushima Prefecture; and their risk perception of the health effects of radiation exposure as stratified by gender and generation.

Methods: Of almost 8000 residents who were 20 years of age or older and who had lived, prior to the accident, in the zones of Tomioka town where residents were permitted to return, 1860 were included in the analysis. For the analysis, the residents were divided into 4 groups which were stratified by gender and age: older males (over 50 years), young males (20-49 years), older females (over 50 years), and young females (20-49 years).

Results: ITR was found to be significantly lower in young males, young females, and older females than in older males. Conversely, young and older females had significantly higher levels of anxiety about drinking tap water and consuming food collected in Tomioka town. Young and older females also had greater concerns about adverse health effects on themselves and their offspring due to living in Tomioka town.

Conclusion: Our results showed that special attention should be paid to younger residents, particularly to young females, with regard to recovery from a nuclear disaster.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/dmp.2020.319DOI Listing
December 2020

Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms.

Acta Med Okayama 2020 Oct;74(5):407-413

Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18926/AMO/60800DOI Listing
October 2020

Comparative efficacy of antitumor necrosis factor agents and tacrolimus in naïve steroid-refractory ulcerative colitis patients.

Sci Rep 2020 07 27;10(1):12546. Epub 2020 Jul 27.

Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.

While retrospective studies have compared the efficacy of anti-tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-68828-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385627PMC
July 2020

Medical Transport for 769 COVID-19 Patients on a Cruise Ship by Japan Disaster Medical Assistance Team.

Disaster Med Public Health Prep 2020 Dec 5;14(6):e47-e50. Epub 2020 Jun 5.

Japan DMAT Secretariat, National Hospital Organization Disaster Medical Center, Tokyo, Japan.

The Diamond Princess cruise ship, carrying 3711 passengers and crew members, docked at Yokohama Port in Japan on February 3, 2020. A quarantine was immediately instituted because 1 passenger who had disembarked in Hong Kong was confirmed to have tested positive for coronavirus disease 2019 (COVID-19). After the quarantine began, all passengers and crew were tested using the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction assay on the ship, 696 of whom tested positive. In total, 769 patients, including 696 with COVID-19, required transport to a hospital. The Japan Disaster Medical Assistance Team (DMAT) successfully picked up and safely transported the COVID-19 patients using a novel classification system to prioritize patients. The Japan DMAT transported 203 patients to hospitals in Kanagawa and another 566 patients to hospitals in 15 different prefectures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/dmp.2020.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298096PMC
December 2020

Protective effects of a cystine and theanine mixture against acute radiation injury in rats.

Environ Toxicol Pharmacol 2020 Aug 17;78:103395. Epub 2020 Apr 17.

Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address:

This study aims to examine the effects of cystine and theanine (CT), which increases glutathione biosynthesis, on the survival rate and acute radiation injury of the small intestine and bone marrow using a rat model. CT pre-treatment (280 mg/kg for 5 days) significantly improved weight loss and survival rate of rats as compared with the control group after 5 Gy. CT pre-treatment significantly increased the rate of mucosa and crypt length, and decreased the number of apoptotic cells, TUNEL and cleaved caspase-3 positive cells, while increasing the number of mitotic cells and Ki-67 positive cells in jejunal crypts and villi compared to control rats post-irradiation. CT also suppressed bone marrow cell loss and reduced the number of apoptotic cells in bone marrow. These results suggest a protective effect of CT pre-treatment for acute injury after irradiation through apoptosis inhibition and increased proliferative activity in jejunal crypt cells and bone marrow cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2020.103395DOI Listing
August 2020

Health-related quality of life in Japanese patients with prostate cancer following proton beam therapy: an institutional cohort study.

Jpn J Clin Oncol 2020 May;50(5):519-527

Department of Global Health, Medicine and Welfare, Nagasaki University Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki, Japan.

Objective: Many treatment options have guaranteed long-term survival in patients with localized prostate cancer and health-related quality of life has become a greater concern for those patients. The purpose of this study was to reveal the health-related quality of life after proton beam therapy and to clarify the differences from other treatment modalities for prostate cancer.

Methods: Between January 2011 and April 2016, 583 patients were enrolled in the study and health-related quality of life outcomes using the Expanded Prostate Cancer Index Composite questionnaire were evaluated and compared with previous research targeted at Japanese patients.

Results: We found a significant decrease in the least square mean scores for urinary and bowel domains excluding the incontinence subscale after proton beam therapy (P < 0.0001) and recovery at a year following treatment. The scores for sexual function in patients without androgen deprivation therapy decreased each year after proton beam therapy (P < 0.0001). The scores for hormones in patients without androgen deprivation therapy remained high and those of patients with androgen deprivation therapy were lower before treatment but were comparable to those of non-androgen deprivation therapy patients at 2 years post-treatment. We found that the impact of radiotherapy including proton beam therapy on urinary condition and sexual function was lower than that of surgery.

Conclusions: For the first time in Japan, we investigated health-related quality of life using Expanded Prostate Cancer Index Composite questionnaires in patients with prostate cancer after proton beam therapy and compared it with other treatment modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyaa027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202140PMC
May 2020

Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16 Expression.

Cancer Control 2020 Jan-Dec;27(1):1073274819901170

Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and its presence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cells increase with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV) were used for double-label immunofluorescence of 53BP1 and Ki-67/p16 expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16 expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern ( < .0001). There was a significant correlation between 53BP1 and p16 expression levels ( = .73, < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1073274819901170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044491PMC
October 2020

Proposal for Reforming Prehospital Response to Chemical Terrorism Disasters in Japan: Going Back to the Basics of Saving the Lives of the Injured by Securing the Safety of the Rescue Team.

Prehosp Disaster Med 2020 Feb 6;35(1):88-91. Epub 2019 Dec 6.

Japan DMAT Secretariat, National Hospital Organization Disaster Medical Center, Tokyo, Japan.

Introduction: Having experienced the Tokyo subway sarin attack in 1995, Japan has established extremely strict rules on handling injured victims before they are sent to a hospital. As a result, it takes a long time before rescue actions are taken. This report aims to propose a reform to change the system that focuses on saving lives.

Methods: First, the issues in firefighting on sites that currently present problems in Japan were identified. Then, Japanese guidelines were compared with those that were considered in other countries. Based on this, an ideal way of running rescue operations was examined, and a proposal to save many lives was made. This research was conducted with funding from the Ministry of Health, Labour, and Welfare of Japan (MHLW; Chiyoda, Tokyo, Japan).

Results: In addition to preventing secondary injuries, the temporal aspect of rescuing people early with the clear goal of saving many lives was emphasized. Priority was given to measures against nerve agents to prevent secondary injuries, which put the rescuers' lives at risk. Possible decontamination methods were pursued before choosing the one that was most appropriate. A linear algorithm was used to determine which decontamination method could be started immediately, and then the gradual use of equipment was recommended. Even if Level A personal protective equipment (PPE) and other dedicated equipment and materials cannot be procured, the possibility of starting rescue activities under certain condition using regular equipment was pointed out. The need for a system for possible victims who would require support, such as foreigners, the handicapped, and elderly people, was also identified. Japan limits the scope of activities that can be undertaken by emergency medical technicians (EMTs) on-site. The way in which on-site medical care can be provided with future legal revisions in mind was also discussed.

Conclusion: There is an urgent need to build a framework in which rescue activities can take place so that the number of deaths would not rise, even if sarin and other poisons are scattered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1049023X19005119DOI Listing
February 2020

Significant association between 53 BP1 expression and grade of intraepithelial neoplasia of esophagus: Alteration during esophageal carcinogenesis.

Pathol Res Pract 2019 Nov 16;215(11):152601. Epub 2019 Aug 16.

Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address:

Background: Abnormal DNA damage response (DDR) leads to genomic instability and carcinogenesis. P53-binding protein 1 (53 BP1), a DDR molecule, is known to accumulate at the sites of DNA double-strand breaks. The aim of this study was to analyze the expression pattern of 53 BP1-nuclear foci (NF) in esophageal neoplasms in order to visualize the state of DDR in esophageal carcinogenesis and to clarify its significance in the molecular pathology of the disease.

Methods: A total of 61 lesions from 22 surgically resected samples of esophageal cancer, including histologically normal squamous epithelium, low-grade intraepithelial neoplasia (LG-IN), high-grade intraepithelial neoplasia (HG-IN), carcinoma in situ (CIS), and invasive squamous cell carcinoma (SCC), were included in the study. 53 BP1 and Ki-67 expression were analyzed by double-labeled immunofluorescence.

Results: The number of discrete 53 BP1-NF increased as the tumor progressed from normal epithelium through LG-IN, HG-IN, CIS, and SCC. 53 BP1-NF larger than 1 μm in diameter (large foci), indicating intensive DDR, also showed a stepwise increase during the progression of carcinogenesis. Of note, large foci of 53 BP1 were found in significantly higher numbers in HG-IN than in LG-IN. Furthermore, localization of 53 BP1-NF in Ki-67-positive cells, indicating the abnormal timing of DDR, also increased with malignancy progression.

Conclusions: 53 BP1-NF accumulation increases during cancer progression from LG-IN to HG-IN to CIS to SCC. Detection of 53 BP1-NF by immunofluorescence, especially large foci, is a feasible method of estimating DNA instability and the malignant potential of esophageal intraepithelial neoplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2019.152601DOI Listing
November 2019

Vulnerability of Pregnant Women After a Disaster: Experiences After the Kumamoto Earthquake in Japan.

Prehosp Disaster Med 2019 10 30;34(5):569-571. Epub 2019 Aug 30.

National Hospital Organization Disaster Medical Center-Institute for Clinical Research, Tachikawa City, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1049023X1900476XDOI Listing
October 2019

Consideration of Medical and Public Health Coordination - Experience from the 2016 Kumamoto, Japan Earthquake.

Prehosp Disaster Med 2019 Apr 14;34(2):149-154. Epub 2019 Apr 14.

1.DMAT Secretariat,Disaster Medical Center of Japan,Tachikawa, Tokyo,Japan.

Objective: The aim of this study was to identify disaster medical operation improvements from the 2016 Kumamoto Earthquake (Kumamoto Prefecture, Japan) and to extract further lessons learned to prepare for future expected major earthquakes.

Methods: The records of communications logs, chronological transitions of chain of command, and team registration logs for the Disaster Medical Assistant Team (DMAT), as well as other disaster medical relief teams, were evaluated.

Results: A total of 466 DMAT teams and 2,071 DMAT team members were deployed to the Kumamoto area, and 1,894 disaster medical relief teams and 8,471 disaster medical relief team member deployments followed. The DMAT established a medical coordination command post at several key disaster hospitals to designate medical coverage areas. The DMAT evacuated over 1,400 patients from damaged hospitals, transported medical supplies to affected hospitals, and coordinated 14 doctor helicopters used for severe patient transport. To keep constant medical and public health operations, DMAT provided medical coordination management until the local medical coordination was on-track. Several logistic teams, which are highly trained on operation and management of medical coordination command, were dispatched to assist management operation. The DMAT also helped to establish Disaster Coordination and Management Council at the prefectural- and municipal-level, and also coordinated command control for public health operations. The DMAT could provide not only medical assistance at the acute phase of the disaster, but also could provide medical coordination for public health and welfare.

Conclusion: During the 2016 Kumamoto Earthquake, needs of public health and welfare increased enormously due to the sudden evacuation of a large number of residents. To provide constant medical assistance at the disaster area, DMAT, logistic teams, and other disaster medical relief teams must operate constant coordination at the medical headquarter command. For future expected major earthquakes in Japan, it will be required to educate and secure high enough numbers of disaster medical assistance and health care personnel to provide continuous medical and public health care for the affected area residents.Kondo H, Koido Y, Kawashima Y, Kohayagawa Y, Misaki M, Takahashi A, Kondo Y, Chishima K, Toyokuni Y. Consideration of medical and public health coordination - experience from the 2016 Kumamoto, Japan Earthquake. Prehosp Disaster Med. 2019;34(2):149-154.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1049023X19000177DOI Listing
April 2019

Nurses' interest in nuclear disaster medicine: future capacity building.

J Radiat Res 2019 05;60(3):333-334

Department of Global Health, Medicine and Welfare, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jrr/rrz008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530613PMC
May 2019

A Novel Diagnostic Method for Thyroid Follicular Tumors Based on Immunofluorescence Analysis of p53-Binding Protein 1 Expression: Detection of Genomic Instability.

Thyroid 2019 05;29(5):657-665

1 Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

The preoperative diagnosis of thyroid follicular carcinomas (FCs) by fine-needle aspiration cytology is almost impossible. It was previously demonstrated that p53-binding protein 1 (53BP1) expression, based on immunofluorescence (IF), can serve as a valuable biomarker to estimate the malignant potential of various cancers. 53BP1 belongs to a class of DNA damage response molecules that rapidly localize to the site of DNA double-strand breaks, forming nuclear foci (NF). This study aimed to elucidate the utility of 53BP1 NF expression as a biomarker to differentiate follicular tumors (FTs). Associations between 53BP1 expression based on IF and histological types of FTs were analyzed using 27 follicular adenomas (FAs), 28 minimally invasive FCs, and 14 widely invasive FCs. Furthermore, the study clarified the relationship between 53BP1 NF and copy number aberrations (CNAs) based on array comparative genomic hybridization, a hallmark of genomic instability (GIN). This study demonstrates differences in 53BP1 NF expression between FA and FC. The incidence of 53BP1 at NF significantly increased with FT progression in the following order: normal follicle < FA < minimally invasive FCs < widely invasive FCs. In contrast, no significant differences were observed in CNAs among the FT samples. Furthermore, there was no significant correlation between CNAs and 53BP1 at NF in FTs. Thus, based on a comparison of these two indicators of GIN, 53BP1 NF (by IF) was better able to estimate the malignancy of FTs compared to CNA (by array comparative genomic hybridization). Interestingly, IF revealed a heterogenous distribution of 53BP1 NF, which occurred more frequently in the invasive or subcapsular area than in the center of the tumor, suggesting intratumoral heterogeneity of GIN in FTs. It is proposed that IF analysis of 53BP1 expression could be a novel diagnostic method to estimate the malignant potential of FTs. Because 53BP1 NF reflect DNA double-strand breaks, it is hypothesized that the incidence of 53BP1 at NF can represent the level of GIN in tumor cells. IF analysis of 53BP1 expression will not only be an auxiliary histologic technique to diagnose FTs accurately, but also a novel technique for preoperative diagnosis using fine-needle aspiration cytology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2018.0548DOI Listing
May 2019

Expression pattern of p53-binding protein 1 as a new molecular indicator of genomic instability in bladder urothelial carcinoma.

Sci Rep 2018 10 19;8(1):15477. Epub 2018 Oct 19.

Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Copy number alterations and loss of heterozygosity are associated with increasing tumor grade and bladder cancer stage. Our previous study suggested that co-expression of Ki-67 and p53-binding protein 1 (53BP1) could provide an indicator of an abnormal DNA damage response (DDR) pathway. The present study investigated 53BP1 expression as a novel molecular marker in urothelial carcinoma (UC) using bladder tissues with in total of 40 cases including a normal urothelium, urothelial papilloma, low-grade UC, or high-grade UC. Double-label immunofluorescence was used to analyze 53BP1 and Ki-67 expression. This was compared with the level of chromosomal instability and with the expression of other DDR molecules catalytic subunit. This study identified clear differences in the 53BP1 expression patterns in urothelial carcinogenesis, and their close association with genomic instability. 53BP1 abnormal immunoreactivity, particularly with co-localization of Ki-67, was restricted to malignant tissues. Our analyses indicated that a cut-off of >4% of nuclei with 53BP1 abnormal expression plus Ki-67 immunoreactivity distinguished high-grade UC from low-grade UC with 80.0% sensitivity and 100% specificity. We therefore propose that double immunofluorescent analysis of 53BP1 and Ki-67 expression could provide a useful tool to estimate the chromosomal instability and malignant potential of urothelial tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-33761-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195620PMC
October 2018

Diversity in intracortical remodeling in the human femoral bone: A novel view point with the morphological analysis of secondary osteons.

J Orthop Sci 2018 Nov 23;23(6):1079-1086. Epub 2018 Aug 23.

Department of Macroscopic Anatomy, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Introduction: In humans, intracortical bone remodeling is performed by a basic multicellular unit (BMU) composed of osteoclasts and osteoblasts penetrating through cortical bones. As a result, secondary osteons and their boundaries, cement lines, can be observed on the transverse section. There have been few reports mention whether there is diversity within a single individual and on the relevance to bone remodeling. The purpose of this study is to investigate the morphological diversity of secondary osteons in human femoral bone and to examine the relationship with bone remodeling.

Material And Methods: First of all, we developed an original method to get the cross-sectional images of the cortical bones around the whole circumference for the purpose of evaluating the morphology of the secondary osteon exhaustively. Then, a total of ten cross-sectional slices from one right human femoral bone of male were prepared and stained with this method. The osteon population density and complexity of cement lines in osteons were evaluated in detail.

Results: Within this femoral bone, the osteon population density was significantly higher in the periosteal side and in the posterior area. Conversely, the cement line density and the osteon complexity were higher in the endosteal side; the proportion of complexed osteon significantly increased from the periosteal side toward the endosteal side.

Discussion: The results suggested that there were diversities in osteon population densities and osteon morphological pattern within one human femoral bone. It seemed that the BMUs ran to avoid the existing regions of osteon in the periosteal sides and to overlap the existing osteon in the endosteal sides. This seemed to be one of the novel viewpoints in the morphological analysis of secondary osteons. It might be better for the orthopedic surgeons to be aware that the osteon distribution in the cortical bone is not uniform.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jos.2018.07.021DOI Listing
November 2018

Investigating interindividual variations in cortical bone quality: analysis of the morphotypes of secondary osteons and their population densities in the human femoral diaphysis.

Anat Sci Int 2019 Jan 30;94(1):75-85. Epub 2018 Jul 30.

Department of Orthopaedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8523, Japan.

Osteons are the primary sites of cortical bone lesions. However, many aspects of osteon microstructure remain poorly understood. This study aimed to explores interindividual differences in the osteon morphotype distributions in the human femoral diaphysis by evaluating the secondary osteon distributions in samples from human femurs. Two anonymized bone fragments from two modern Japanese femurs were examined. Twelve continuous transverse femoral diaphysis specimens were prepared from each fragment. Imaging examinations were conducted using a circularly polarized light microscope, and cross-sectional images were rendered using graphical synthesis software. Osteons in the images were identified as either bright-type osteons, dark-type osteons, or an others type. The two femurs were compared, and the secondary osteon morphotype distributions in different regions of their cross-sections were analyzed. When the two femurs were compared, significant differences in osteon density were observed in some regions and cross-sections. The dark-type osteon presence was strongest in the anterior and posterior regions of the femurs. The analytical method used in this study was found to be able to evaluate osteon microstructure. The results suggest that examining additional specimens and analyzing the biomechanical underpinnings of interindividual differences in osteon distribution patterns may help to improve our understanding of osteon microstructure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12565-018-0452-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315013PMC
January 2019

Aeromedical Transport Operations Using Helicopters during the 2016 Kumamoto Earthquake in Japan.

J Nippon Med Sch 2018 ;85(2):124-130

Institute for Clinical Research National Disaster Medical Center.

More than 6,000 people died in the Great Hanshin (Kobe) Earthquake in 1995, and it was later reported that there were around 500 preventable trauma deaths. In response, the Japanese government developed the helicopter emergency medical service in 2001, known in Japan as the "Doctor-Heli" (DH), which had 46 DHs and 2 private medical helicopters as of April 2016. DHs transport physicians and nurses to provide pre-hospital medical care at the scene of medical emergencies. Following lessons learned in the Great East Japan Earthquake in 2011, a research group in the Ministry of Health, Labour and Welfare developed a command and control system for the DH fleet as well as the Disaster Relief Aircraft Management System Network (D-NET), which uses a satellite communications network to monitor the location of the fleet and weather in real-time during disasters. During the Kumamoto Earthquake disaster in April 2016, 75 patients were transported by 13 DHs and 1 private medical helicopter in the first 5 days. When medical demand for the DHs exceeded supply, 5 patients, 8 patients, and 1 patient were transported by Self-Defense Force, Fire Department, and Coast Guard helicopters, respectively. Of the 89 patients who were transported, 30 (34%) had trauma, 3 (3%) had pulmonary embolisms caused by sleeping in vehicles, and 17 (19%) were pregnant women or newborns. This was the first time that the command and control system for aeromedical transport and D-NET, established after the Great East Japan Earthquake in 2011, were operated in an actual large-scale disaster. Aeromedical transport by DHs and helicopters belonging to several other organizations was accomplished smoothly because the commanders of the involved organizations could communicate directly with each other in person within the Aviation Coordination Section of the prefectural government office. However, ongoing challenges in the detailed operating methods for aeromedical transport were highlighted and include improving shared knowledge and training across the organizational framework. These are particularly important issues to address given the Nankai Trough and Tokyo inland earthquakes that are predicted for the near future in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1272/jnms.2018_85-19DOI Listing
August 2018

Investigation of Japan Disaster Medical Assistance Team response guidelines assuming catastrophic damage from a Nankai Trough earthquake.

Acute Med Surg 2017 07 24;4(3):300-305. Epub 2017 Apr 24.

Japan DMAT Secretariat National Hospital Organization Disaster Medical Center Tokyo Japan.

Aim: Transporting critically ill patients outside of disaster-affected areas for treatment is an important activity of Japan Disaster Medical Assistance Teams (DMATs). We investigated whether this activity is possible after possible catastrophic damage from a Nankai Trough earthquake.

Methods: Japan was divided into three areas based on the level of predicted damage (definitely, possibly, and non-affected areas). A survey of DMATs and the locations of emergency base hospitals and intensive care units (ICUs) in each area was carried out, and the ability to support disaster areas was investigated. Next, a survey of wide-area medical transport by Self-Defense Force aircraft and the medical transport abilities of helicopter ambulances was carried out. The numbers of ICU beds in each area were compared, and the capacity to accept patients was investigated. Finally, subjects for further study were examined.

Results: The number of DMATs that could be sent from non-affected areas was insufficient. The number of patients that can be transported by Self-Defense Force aircraft and helicopter ambulance during the first 3 days was determined to be 1,443. The number of patients that can be accepted by ICUs in non-affected areas was insufficient. A system needs to be developed to provide medical treatment for critically ill patients within disaster areas during the acute phase. This will require DMAT operational reforms and the creation of logistics systems such as the supply of resources for earthquake-reinforced hospitals.

Conclusion: In addition to patient transport, systems to provide medical care inside disaster-affected areas are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ams2.280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674451PMC
July 2017

Cancer mortality in residents of the terrain-shielded area exposed to fallout from the Nagasaki atomic bombing.

J Radiat Res 2018 Jan;59(1):1-9

Department of Global Health, Medicine and Welfare, Atomic Bomb Disease Institute, Nagasaki University, 12-4 Sakamoto 1-chome, Nagasaki 852-8523, Japan.

The health effects of radiation exposure from the atomic bomb fallout remain unclear. The objective of the present study is to elucidate the association between low-dose radiation exposure from the atomic bomb fallout and cancer mortality among Nagasaki atomic bomb survivors. Of 77 884 members in the Nagasaki University Atomic Bomb Survivors Cohort, 610 residents in the terrain-shielded area with fallout were selected for this analysis; 1443 residents in the terrain-shielded area without fallout were selected as a control group; and 3194 residents in the direct exposure area were also selected for study. Fifty-two deaths due to cancer in the terrain-shielded fallout area were observed during the follow-up period from 1 January 1970 to 31 December 2012. The hazard ratio for cancer mortality in the terrain-shielded fallout area was 0.90 (95% confidence interval: 0.65-1.24). No increase in the risk of cancer mortality was observed, probably because the dose of the radiation exposure was low for residents in the terrain-shielded fallout areas of the Nagasaki atomic bomb, and also because the number of study subjects was small.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jrr/rrx047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778598PMC
January 2018

Hepatitis C Virus Infection Increases c-Jun N-Terminal Kinase (JNK) Phosphorylation and Accentuates Hepatocyte Lipoapoptosis.

Med Sci Monit 2017 Sep 21;23:4526-4532. Epub 2017 Sep 21.

Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan.

BACKGROUND Hepatitis C virus (HCV) infection and metabolic diseases including nonalcoholic steatohepatitis (NASH) exhibit a complex interplay. Although free fatty acid-mediated apoptosis is a prominent feature of NASH, the impact of HCV infection on hepatocyte lipotoxicity has remained largely unexplored. The study aimed at identifying whether infection by HCV affected the apoptotic pathway in hepatocytes during fatty acid assault. MATERIAL AND METHODS OR6 cells, which are derived from human hepatocellular carcinoma Huh-7 cells and harbor a full-length HCV RNA genome replication system, were treated with palmitate. Apoptosis was examined by 4',6-diamidino-2-phenylindole staining. Activation and expression of JNK, Bim, cIAP-1, and Mcl-1 were examined by immunoblotting. mRNA expression of CHOP, a major player in endoplasmic reticulum stress-mediated apoptosis, was assessed by real-time PCR. RESULTS Palmitate-induced hepatocyte apoptosis was significantly enhanced in OR6 cells compared to cured cells, in which the HCV genome had been eradicated by treatment with interferon-α. Although basal expression of CHOP mRNA was enhanced in OR6 cells compared to cured cells, it was similarly upregulated in both cell lines following palmitate treatment. Notably, palmitate-induced JNK phosphorylation was accentuated in OR6 cells compared to cured cells. Inhibition of JNK with SP600125 attenuated palmitate-induced apoptosis. Palmitate-mediated upregulation of BH3-only protein Bim, which acts downstream of JNK, was also enhanced in OR6 cells compared to cured cells. In contrast, Mcl-1 and cIAP-1 were equally reduced in OR6 cells and cured cells following palmitate treatment. CONCLUSIONS These findings suggest that during lipoapoptosis, HCV infection may enhance hepatocyte toxicity by increasing JNK phosphorylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621789PMC
http://dx.doi.org/10.12659/msm.903210DOI Listing
September 2017

Lessons learned from the total evacuation of a hospital after the 2016 Kumamoto Earthquake.

J Emerg Manag 2017 Jul/Aug;15(4):259-263

Self Defense Force, Kumamoto Hospital, Kumaoto, Japan.

Background: The 2016 Kumamoto Earthquakes were a series of earthquakes that included a foreshock earthquake (magnitude 6.2) on April 14 and a main shock (magnitude 7.0) on April 16, 2016. A number of hospitals in Kumamoto were severely damaged by the two major earthquakes and required total evacuation.

Methods: The authors retrospectively analyzed the activity data of the Disaster Medical Assistance Teams using the Emergency Medical Information System records to investigate the cases in which the total evacuation of a hospital was attempted following the 2016 Kumamoto Earthquake.

Results: Total evacuation was attempted at 17 hospitals. The evacuation of one of these hospitals was canceled. Most of the hospital buildings were more than 20 years old. The danger of collapse was the most frequent reason for evacuation. Various transportation methods were employed, some of which involved the Japan Ground Self-Defense Force; no preventable deaths occurred during transportation.

Conclusions: The hospitals must now be renovated to improve their earthquake resistance. The coordinated and combined use of military and civilian resources is beneficial and can significantly reduce human suffering in large-scale disasters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5055/jem.2017.0334DOI Listing
April 2018

Body Surface Contamination Levels of Residents under Different Evacuation Scenarios after the Fukushima Daiichi Nuclear Power Plant Accident.

Health Phys 2017 09;113(3):175-182

*Department of Radiation Health Management, Fukushima Medical University, Fukushima, Japan; †ISGlobal (Institut de Salut Global de Barcelona), Barcelona, Spain; ‡Department of Radiation Disaster Mediceine, Fukushima Medical University, Fukushima, Japan; §National Hospital Organization Disaster Medical Center, Tokyo, Japan; **International University of Health and Welfare Clinic, Tochigi, Japan.

Body surface contamination levels should be correlated with inhaled actual thyroid doses during evacuation following the Fukushima Daiichi nuclear power plant (FDNPP) accident. Evacuees and residents were screened for body surface contamination using a Geiger-Mueller survey meter. The authors obtained 7,539 individual screening data sheets as well as gamma-spectrometry data from measurements made on clothing of two subjects by using a germanium spectrometer. Body surface contamination levels were analyzed in four residential groups during two different periods: 12-14 and 15-17 March 2011. Contamination levels during 12-14 March in the Tomioka/Okuma/Futaba/Naraha group were very low, indicating that residents evacuated before the radioactive plume reached their towns on 12 March. In contrast, levels in the Namie and Minamisoma groups were higher than those in the other groups in both periods, indicating that these residents were exposed to plumes twice on 12 and 15-16 March. The plume on 12 March was enriched with short-lived radionuclides: averaged proportions of radioactivity (relative to I) from Te, I, and Cs measured in clothing from two subjects were 2.3, 1.1, and 0.1, respectively, after correction for physical decay by 12:00 on 12 March. These proportions are similar to those (relative to I) from Te and Cs in dust sampled by a high-volume air sampler in the zone 20 km from the FDNPP on 12 March: 1.9 and 0.1, respectively. These data indicate that the relative contribution to inhaled thyroid dose of short-lived radionuclides in radioactive plumes released on 12 March could be as much as 37.5% in 1-y-old children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HP.0000000000000690DOI Listing
September 2017

Survey of Preventable Disaster Deaths at Medical Institutions in Areas Affected by the Great East Japan Earthquake: Retrospective Survey of Medical Institutions in Miyagi Prefecture.

Prehosp Disaster Med 2017 Oct 9;32(5):515-522. Epub 2017 May 9.

6Division of Emergency and Critical Care Medicine,Tohoku University Graduate School of Medicine,Sendai,Japan.

Introduction In 2015, the authors reported the results of a preliminary investigation of preventable disaster deaths (PDDs) at medical institutions in areas affected by the Great East Japan Earthquake (2011). This initial survey considered only disaster base hospitals (DBHs) and hospitals that had experienced at least 20 patient deaths in Miyagi Prefecture (Japan); therefore, hospitals that experienced fewer than 20 patient deaths were not investigated. This was an additional study to the previous survey to better reflect PDD at hospitals across the entire prefecture.

Method: Of the 147 hospitals in Miyagi Prefecture, the 14 DBHs and 82 non-DBHs that agreed to participate were included in an on-site survey. A database was created based on the medical records of 1,243 patient deaths that occurred between March 11, 2011 and April 1, 2011, followed by determination of their status as PDDs.

Results: A total of 125 cases of PDD were identified among the patients surveyed. The rate of PDD was significantly higher at coastal hospitals than inland hospitals (17.3% versus 6.3%; P<.001). Preventable disaster deaths in non-DBHs were most numerous in facilities with few general beds, especially among patients hospitalized before the disaster in hospitals with fewer than 100 beds. Categorized by area, the most frequent causes of PDD were: insufficient medical resources, disrupted lifelines, delayed medical intervention, and deteriorated environmental conditions in homes and emergency shelters in coastal areas; and were delayed medical intervention and disrupted lifelines in inland areas. Categorized by hospital function, the most frequent causes were: delayed medical intervention, deteriorated environmental conditions in homes and emergency shelters, and insufficient medical resources at DBHs; while those at non-DBHs were disrupted lifelines, insufficient medical resources, delayed medical intervention, and lack of capacity for transport within the area.

Conclusion: Preventable disaster death at medical institutions in areas affected by the Great East Japan Earthquake occurred mainly at coastal hospitals with insufficient medical resources, disrupted lifelines, delayed medical intervention, and deteriorated environmental conditions in homes and emergency shelters constituting the main contributing factors. Preventing PDD, in addition to strengthening organizational support and functional enhancement of DBHs, calls for the development of business continuity plans (BCPs) for medical facilities in directly affected areas, including non-DBHs. Yamanouchi S , Sasaki H , Kondo H , Mase T , Otomo Y , Koido Y , Kushimoto S . Survey of preventable disaster deaths at medical institutions in areas affected by the Great East Japan Earthquake: retrospective survey of medical institutions in Miyagi Prefecture. Prehosp Disaster Med. 2017;32(5):515-522.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1049023X17006501DOI Listing
October 2017

Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1.

Sci Rep 2017 02 3;7:41812. Epub 2017 Feb 3.

Department of Radiation Biology and Protection, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Chromosome rearrangement is clinically and physiologically important because it can produce oncogenic fusion genes. Chromosome rearrangement requires DNA double-strand breaks (DSBs) at two genomic locations and misrejoining between the DSBs. Before DSB misrejoining, two DSB-containing chromatin regions move and pair with each other; however, the molecular mechanism underlying this process is largely unknown. We performed a spatiotemporal analysis of ionizing radiation-induced foci of p53-binding protein 1 (53BP1), a marker for DSB-containing chromatin. We found that some 53BP1 foci were paired, indicating that the two damaged chromatin regions neighboured one another. We searched for factors regulating the foci pairing and found that the number of paired foci increased when Ku80, DNA-PKcs, or ATM was absent. In contrast, 53BP1 depletion reduced the number of paired foci and dicentric chromosomes-an interchromosomal rearrangement. Foci were paired more frequently in heterochromatin than in euchromatin in control cells. Additionally, the reduced foci pairing in 53BP1-depleted cells was rescued by concomitant depletion of a heterochromatin building factor such as Krüppel-associated box-associated protein 1 or chromodomain helicase DNA-binding protein 3. These findings indicate that pairing between DSB-containing chromatin regions was suppressed by Ku80, DNA-PKcs, and ATM, and this pairing was promoted by 53BP1 through chromatin relaxation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep41812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290537PMC
February 2017

Clinical features and prognosis of patients with myelodysplastic syndromes who were exposed to atomic bomb radiation in Nagasaki.

Cancer Sci 2016 Oct 2;107(10):1484-1491. Epub 2016 Sep 2.

Department of Hematology, Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

There is evidence that radiation exposure is a causative factor of myelodysplastic syndromes (MDS). However, little is known about whether radiation exposure is also a prognostic factor of MDS. We investigated the impact of radiation exposure on the prognosis of MDS in Nagasaki atomic bomb survivors using the International Prognostic Scoring System (IPSS) and the revised version (IPSS-R). Subjects were 140 patients with primary MDS diagnosed between 1985 and 2011 and evaluable for IPSS, IPSS-R, and exposure distance. Of those, 31 were exposed at <1.5 km, 35 at 1.5-2.99 km, and 74 at ≥3.0 km. By the end of March 2014, 47 patients (34%) progressed to overt leukemia and 106 (75.7%) died. By comparing with patients exposed at ≥3.0 km, those exposed at <1.5 km had significantly higher frequencies of abnormal chromosome (P = 0.02), intermediate/poor IPSS, and intermediate/poor/very poor IPSS-R cytogenetic category (P = 0.0001, and P < 0.0001, respectively). As with de novo MDS, multivariate Cox regression analyses revealed that cytogenetic abnormalities, IPSS karyotype, and IPSS-R cytogenetics were significantly associated with poor survival, and cumulative incidence of leukemic transformation in MDS among atomic bomb survivors, but exposure distance was not associated with any poor outcomes. These suggest that exposure to the greater dose of atomic bomb radiation is associated with developing poor cytogenetic abnormalities in MDS, which might consequently lead to overt leukemia among atomic bomb survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.13025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084675PMC
October 2016

Development of Mass-casualty Life Support-CBRNE (MCLS-CBRNE) in Japan.

Prehosp Disaster Med 2016 Oct 17;31(5):547-50. Epub 2016 Aug 17.

1Emergency Medical Center,Fujisawa City Hospital,Kanagawa,Japan.

This report outlines the need for the development of an advanced course in mass-casualty life support (MCLS) and introduces the course content. The current problems with education on disasters involving chemical agents, biological agents, radiation/nuclear attacks, or explosives (CBRNE) in Japan are presented. This newly developed "MCLS-CBRNE" program was created by a Ministry of Health, Labour, and Welfare (Tokyo, Japan) research group based on these circumstances. Modifications were then made after a trial course. Training opportunities for relevant organizations to learn how to act at a CBRNE disaster site currently are lacking. The developed course covers initial responses at a disaster site. This one-day training course comprises lectures, three tabletop simulations, and practical exercises in pre-decontamination triage and post-decontamination triage. With regard to field exercises conducted to date, related organizations have experienced difficulties in understanding each other and adapting their approaches. Tabletop simulations provide an opportunity for participants to learn how organizations working on-site, including fire, police, and medical personnel, act with differing goals and guiding principles. This course appears useful as a means for relevant organizations to understand the importance of developing common guidelines. The MCLS-CBRNE training is proposed to support CBRNE disaster control measures during future events. Anan H , Otomo Y , Kondo H , Homma M , Koido Y , Morino K , Oshiro K , Harikae K , Akasaka O . Development of mass-casualty life support-CBRNE (MCLS-CBRNE) in Japan. Prehosp Disaster Med. 2016;31(5):547-550.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1049023X16000686DOI Listing
October 2016