[Show abstract][Hide abstract] ABSTRACT: Radiocesium nuclides, used as a gamma ray source in various types of industrial equipments and found in nuclear waste, are strictly controlled to avoid their leakage into the environment. When large amounts of radiocesium are accidentally incorporated into the human body, decorporation therapy should be considered. Although standard decorporation methods have been studied since the 1960s and were established in the 1970s with the drug Radiogardase® (a Prussian blue preparation), application of recent advances in pharmacokinetics and ethical standards could improve these methods. Here we designed a modern dosage form of hydrogel containing cesium-absorbents to alleviate intestinal mucosa irritation due to the cesium-binding capacity of the absorbents. The effectiveness of the dosage form on fecal excretion was confirmed by quantitative mouse experiments. The total cesium excretion rate of the crystal form (1.37 ± 0.09) was improved by the hydrogel form (1.52 ± 0.10) at the same dose of Prussian blue, with a longer gastrointestinal tract transit time. Using a mouse model, we compared the effects of several drugs on fecal and urinary excretion of internal cesium, without the use of absorbents. Only phenylephrine hydrochloride significantly enhanced cesium excretion (excretion rate of 1.17 ± 0.08) via the urinary pathway, whereas none of the diuretic drugs tested had this effect. These findings indicate that modifying the dosage form of cesium absorbents is important for the decorporation of internal radiocesium contamination.
[Show abstract][Hide abstract] ABSTRACT: Biodosimetry, the measurement of radiation damage in a biologic sample, is a reliable tool for increasing the accuracy of
dose estimation. Although established chromosome analyses are suitable for estimating the absorbed dose after high-dose irradiation,
biodosimetric methodology to measure damage following low-dose exposure is underdeveloped. RNA analysis of circulating blood
containing radiation-sensitive cells is a candidate biodosimetry method. Here we quantified RNA from a small amount of blood
isolated from mice following low-dose body irradiation (<0.5 Gy) aimed at developing biodosimetric tools for situations that
are difficult to study in humans. By focusing on radiation-sensitive undifferentiated cells in the blood based on Myc RNA expression, we quantified the relative levels of RNA for DNA damage-induced (DDI) genes, such as Bax, Bbc3 and Cdkn1a. The RNA ratios of DDI genes/Myc in the blood increased in a dose-dependent manner 4 h after whole-body irradiation at doses ranging from 0.1 to 0.5 Gy (air-kerma)
of X-rays, regardless of whether the mice were in an active or resting state. The RNA ratios were significantly increased
after 0.014 Gy (air-kerma) of single X-ray irradiation. The RNA ratios were directly proportional to the absorbed doses in
water ranging from 0.1 to 0.5 Gy, based on gamma-irradiation from 137Cs. Four hours after continuous irradiation with gamma-rays or by internal contamination with a beta-emitter, the increased
RNA ratios resembled those following single irradiation. These findings indicate that the RNA status can be utilized as a
biodosimetric tool to estimate low-dose radiation when focusing on undifferentiated cells in blood.
Preview · Article · Nov 2015 · Journal of Radiation Research
[Show abstract][Hide abstract] ABSTRACT: Hazardous chemical, radiological, and nuclear materials threaten public health in scenarios of accidental or intentional release which can lead to external contamination of people. Without intervention, the contamination could cause severe adverse health effects, through systemic absorption by the contaminated casualties as well as spread of contamination to other people, medical equipment, and facilities. Timely decontamination can prevent or interrupt absorption into the body and minimize opportunities for spread of the contamination, thereby mitigating the health impact of the incident. Although the specific physicochemical characteristics of the hazardous material(s) will determine the nature of an incident and its risks, some decontamination and medical challenges and recommended response strategies are common among chemical and radioactive material incidents. Furthermore, the identity of the hazardous material released may not be known early in an incident. Therefore, it may be beneficial to compare the evidence and harmonize approaches between chemical and radioactive contamination incidents. Experts from the Global Health Security Initiative’s Chemical and Radiological/Nuclear Working Groups present here a succinct summary of guiding principles for planning and response based on current best practices, as well as research needs, to address the challenges of managing contaminated casualties in a chemical or radiological/nuclear incident.
[Show abstract][Hide abstract] ABSTRACT: Estimating the early internal doses to residents in the Fukushima Daiichi Nuclear Power Station accident is a difficult task because limited human/environmental measurement data are available. Hence, the feasibility of using atmospheric dispersion simulations created by the Worldwide version of System for Prediction of Environmental Emergency Dose Information 2nd Version (WSPEEDI-II) in the estimation was examined in the present study. This examination was done by comparing the internal doses evaluated based on the human measurements with those calculated using time series air concentration maps ((131)I and (137)Cs) generated by WSPEEDI-II. The results showed that the latter doses were several times higher than the former doses. However, this discrepancy could be minimised by taking into account personal behaviour data that will be available soon. This article also presents the development of a prototype system for estimating the internal dose based on the simulations.
[Show abstract][Hide abstract] ABSTRACT: To contribute to the reconstruction and revitalization of Fukushima Prefecture following the 2011 nuclear power disaster, annual individual doses were estimated for evacuees who will return home to Tamura City, Kawauchi Village, and Iitate Village in Fukushima. Ambient external dose rates and individual doses obtained with personal dosimeters were measured at many residential and occupational sites throughout the study areas to obtain fundamental data needed for the estimation. The measurement results indicated that the ratio of individual dose based on a personal dosimeter to the ambient external dose measurement was 0.7 with 10% uncertainty. Multiplying the ambient external dose by 0.7 may be an appropriate measure of the effective dose to an individual in the investigated area. Annual individual doses were estimated for representative lifestyles and occupations based on the ambient external dose rates at the measurement sites, taking into account the relationship between the ambient external dose and individual dose. The results were as follows: 0.6-2.3 mSv y in Tamura, 1.1-5.5 mSv y in Kawauchi, and 3.8-17 mSv y in Iitate. For all areas investigated, the estimated dose to outdoor workers was higher than that to indoor workers. Identifying ways to reduce the amount of time that an outdoor worker spends outdoors would provide an effective measure to reduce dose.
[Show abstract][Hide abstract] ABSTRACT: After the accident at the Fukushima Daiichi Nuclear Power Plant run by Tokyo Electric Power Company in 2011, breast milk samples obtained from volunteers living in Fukushima and neighboring prefectures were examined and small amounts of I-131 (2.2-36.3 Bq/kg) were detected in some samples. In this work, the I-131 concentrations in breast milk from nursing mothers in Ibaraki prefecture were calculated based on the iodine biokinetic model during lactation together with time-variable intake scenarios by inhalation of ambient air and ingestion of tap water, using the authors' code. The calculated I-131 concentrations in breast milk generally agreed with those measured for the volunteers. Based on the results, thyroid equivalent doses to breast-fed infants were estimated for each place of residence of the volunteers on the assumption that these infants consumed 800 ml of breast milk every day, resulting in 10-11 mSv for Mito and Kasama cities and 1.1-1.8 mSv for Tsukuba and Moriya cities. It was suggested that breast milk consumption could be a major contributor to internal dose of breast-fed infants in areas with mild I-131 pollution; however, further studies considering personal behavior surveys would be necessary to estimate individual doses.
[Show abstract][Hide abstract] ABSTRACT: One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial
cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In
order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial
expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of
auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein
(TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial
cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation.
Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also
for rescuing the GI system from radiation injuries.
Preview · Article · Oct 2014 · Journal of Radiation Research
[Show abstract][Hide abstract] ABSTRACT: A huge earthquake struck the northeast coast of the main island of Japan on 11 March 2011, triggering a tsunami with more than 10-m-high waves hitting the area. The earthquake was followed by numerous sustained aftershocks. The earthquake and aftershocks left almost 16,000 people dead and more than 2,800 missing (as of 11 March 2014). The earthquake affected the Fukushima Daiichi Nuclear Power Plant (NPP) of Tokyo Electric Power Company (TEPCO), causing serious damage to the NPP and resulting in large amounts of radioactive materials being released into not only controlled areas but also the environment. Damage was caused to the cooling systems of the NPP, although they automatically shut down after the earthquake. The trouble with the cooling systems led to hydrogen explosions and core meltdown. The major nuclides released on land were I, Cs, and Cs. The release of these radioactive materials resulted in contamination of first responders and workers and also a high ambient dose of radiation around the NPP. The local hospital system, including that for radiation emergency medicine, was dysfunctional. Hospitals that had been designated as radiation emergency facilities were not able to function because the earthquake and tsunami had caused damage to their facilities; some of these were located within a 20-km radius of the NPP and in the evacuation areas. Local fire department personnel were also ordered to evacuate. Fukushima prefecture changed the screening level required for decontamination from 13,000 to 100,000 cpm, with decontamination by wiping being performed for over 13,000 cpm. However, as hospitals and fire departments had to abide by lower levels than that of the prefecture for receiving or transporting contaminated patients, these personnel could not accept or transport contaminated people from the NPPs. In addition, hospitals not designated as radiation emergency facilities would not receive patients from the NPPs because of concerns about the health effects of radiation. From this disaster, it was learned that basic knowledge of radiation and its effects is extremely important for health care providers.
[Show abstract][Hide abstract] ABSTRACT: A huge earthquake struck the northeast coast of the main island of Japan on March 11, 2011, triggering a tsunami with 14-15 meter-high waves hitting the area. The earthquake was followed by numerous sustained aftershocks. The earthquake affected the nuclear power plant (NPP) in Fukushima prefecture, resulting in large amounts of radioactive materials being released into the environment. The major nuclides released on land were (131) I, (134) Cs, and (137) Cs. Therefore, almost 170 000 people had to be evacuated or stay indoors. Besides the NPP and the telecommunications system, the earthquake also affected infrastructures such as the supplies of water and electricity as well as the radiation monitoring system. The local hospital system was dysfunctional; hospitals designated as radiation-emergency facilities were not able to function because of damage from the earthquake and tsunami, and some of them were located within a 20 km radius of the NPP, the designated evacuation zone. Local fire department personnel were also asked to evacuate. Furthermore, the affected hospitals had not established their evacuation plans at that time. We have learned from this "combined disaster" that the potential for damage to lifelines as well as the monitoring systems for radiation in case of an earthquake requires our intense focus and vigilance, and that hospitals need comprehensive plans for evacuation, including patients requiring life support equipment during and after a nuclear disaster. There is an urgent need for a "combined disaster" strategy, and this should be emphasized in current disaster planning and response.
Preview · Article · Feb 2014 · Drug Development Research
[Show abstract][Hide abstract] ABSTRACT: At the outset of the accident at Fukushima Daiichi Nuclear Power Plant in March 2011, the radiation doses experienced by residents were calculated from the readings at monitoring posts, with several assumptions being made from the point of view of protection and safety. However, health effects should also be estimated by obtaining measurements of the individual radiation doses. The individual external radiation doses, determined by a behavior survey in the "evacuation and deliberate evacuation area" in the first 4 months, were <5 mSv in 97.4% of residents (maximum: 15 mSv). Doses in Fukushima Prefecture were <3 mSv in 99.3% of 386,572 residents analyzed. External doses in Fukushima City determined by personal dosimeters were <1 mSv/3 months (September-November, 2011) in 99.7% of residents (maximum: 2.7 mSv). Thyroid radiation doses, determined in March using a NaI (TI) scintillation survey meter in children in the evacuation and deliberate evacuation area, were <10 mSv in 95.7% of children (maximum: 35 mSv). Therefore, all doses were less than the intervention level of 50 mSv proposed by international organizations. Internal radiation doses determined by cesium-134 ((134)C) and cesium-137 ((137)C) whole-body counters (WBCs) were <1 mSv in 99% of the residents, and the maximum thyroid equivalent dose by iodine-131 WBCs was 20 mSv. The exploratory committee of the Fukushima Health Management Survey mentions on its website that radiation from the accident is unlikely to be a cause of adverse health effects in the future. In any event, sincere scientific efforts must continue to obtain individual radiation doses that are as accurate as possible. However, observation of the health effects of the radiation doses described above will require reevaluation of the protocol used for determining adverse health effects. The dose-response relationship is crucial, and the aim of the survey should be to collect sufficient data to confirm the presence or absence of radiation health effects. In particular, the schedule of decontamination needs reconsideration. The decontamination map is determined based on the results of airborne monitoring and the radiation dose calculated from readings taken at the monitoring posts at the initial period of the accident. The decontamination protocol should be reevaluated based on the individual doses of the people who desire to live in those areas.
[Show abstract][Hide abstract] ABSTRACT: The biological dose of nuclear workers engaged in emergency response tasks at Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Station was estimated in the present study. As the national core center for radiation emergency medical preparedness in Japan, the National Institute of Radiological Sciences (NIRS) received all individuals who were suspected of being overexposed to acute radiation. In the course of health examinations at NIRS, biological dosimetry was performed by the dicentric chromosome assay (DCA). Twelve individuals were examined from 21 March-1 July 2011. The results indicated that the estimated exposure doses for all individuals were lower than 300 mGy, with the mean value of about 101 mGy. These results by DCA were in accordance with those obtained by physical dosimetry based on personal dosimeter recording assessment. The results corroborate the fact that no acute radiation syndrome was observed among the workers examined.
[Show abstract][Hide abstract] ABSTRACT: On 11 March 2011, the Great Eastern Japan Earthquake occurred, causing the accident at the Fukushima Daiichi Nuclear Power Plant of Tokyo Electric Power Co. Residents were surveyed for contamination, and hospitalized patients within a 30-km area were transferred. In this report, the authors review the results of the survey and the effects. The screening teams measured total body contamination of each person using a Geiger-Mueller survey meter. Decontamination level was set at 100 kcpm (100,000 cpm). For levels of 13 to <100 kcpm, decontamination by wiping was planned and took place. Contamination screening during 11–21 March 2011, was carried out for 72,660 people at 200 sites. From 12 March 2011 until 10 February 2012, a total of 244,281 people were screened. As a result, there were 110 cases exceeding 100 kcpm, and 901 cases with contamination levels of 13–100 kcpm. The number of contaminated individuals screened reached a peak from 16–18 March. In the accident, contamination screening of victims and residents was performed to deal with anxiety and discrimination toward the residents. Although there was some early delay, almost all of the evacuees were relatively promptly screened. There was no external contamination at levels thought to affect the health of residents. In addition, the detection of contamination levels over 13 kcpm peaked between 15–22 March. Considering factors such as the evacuation period, this suggests that even if iodine tablets had been administered during this time, they would not have been effective.
[Show abstract][Hide abstract] ABSTRACT: Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP.While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information.Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled.It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendations to minimise such lapses in communication.
Full-text · Article · Jun 2013 · Journal of Radiological Protection
[Show abstract][Hide abstract] ABSTRACT: Accidental exposure of the abdomen to high-dose radiation leads to severe consequences initiated by disruption of the mucosa
in the small intestine. Therapeutic options are limited, even though various treatments have been investigated, particularly
in the field of regenerative therapy. In order to identify readily available treatment methods, we included several current
pharmaceutical drugs, for which the clinical trials have already been completed, in tests on mice that had undergone severe
mucosal damage by radiation. The drugs were injected into mice 24 h after exposure to 15.7 Gy X-rays. The effects of the drugs
on the damaged mucosa of the small intestine were evaluated using early regeneration indices [the expression of c-myb mRNA, and proliferation of epithelial cells in the form of microcolonies (MCs) by Days 4 and 5 post-irradiation] and the
survival rate of the mice. Enhancement of mucosal regeneration at Day 4 (c-myb: P < 0.01, MC: P < 0.05) and improvement of the survival rate (P < 0.05) were observed when a clinical dose of gonadotropin, a stimulator of androgen, was injected. Similarly, a clinical
dose of thiamazole (which prevents secretion of thyroid hormone) stimulated mucosal growth by Day 5 (c-myb: P < 0.01, MC: P < 0.05) and also improved the survival rate (P < 0.05). The nonclinical drugs histamine and high-dose octreotide (a growth hormone antagonist) also gave significant survival-enhancing
benefits (P < 0.01 and P < 0.05, respectively). These results can be used to construct therapeutic programs and applied in various experimental studies
to control the regeneration of damaged mucosa.
Preview · Article · May 2013 · Journal of Radiation Research
[Show abstract][Hide abstract] ABSTRACT: The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Sensitivity to a tyrosine kinase inhibitor (TKI) is correlated with the presence of somatic mutations that affect the kinase domain of epidermal growth factor receptor (EGFR). Development of resistance to TKI is a major therapeutic problem in non-small cell lung cancer (NSCLC). Aim of this study is to identify agents that can overcome TKI resistance in NSCLC.
We used a carefully selected panel of 12 NSCLC cell lines to address this clinical problem. Initially, the cell lines were treated with a variety of 10 compounds. Cellular proliferation was measured via MTT assay. We then focused on the gefitinib-resistant, EGFR mutant cell lines [H1650: exon 19 and PTEN mutations; and H1975: exons 20 (T790M) and 21 (L858R)] to identify agents that could overcome TKI resistance.
Both 17-DMAG (Hsp90 inhibitor) and belinostat (histone deacetylase inhibitor, HDACi) effectively decreased the growth of almost all NSCLC lines. Also, belinostat markedly decreased the expression of EGFR and phospho-Akt in the cells. Combination of 17-DMAG and belinostat synergistically inhibited in vitro proliferation of these cells. Furthermore, both agents and their combination almost completely prevented TKI-resistant tumor formation (EGFR T790M mutation) in a xenograft model.
These results suggest that the combination of 17-DMAG and belinostat should be examined in a clinical trial for TKI-resistant NSCLC cell.
Full-text · Article · Mar 2013 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Background:
The accidents that occurred at the Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake on 11 March 2011 have resulted in long-term, ongoing anxiety among the residents of Fukushima, Japan. Soon after the disaster, Fukushima Prefecture launched the Fukushima Health Management Survey to investigate long-term low-dose radiation exposure caused by the accident. Fukushima Medical University took the lead in planning and implementing this survey. The primary purposes of this survey are to monitor the long-term health of residents, promote their future well-being, and confirm whether long-term low-dose radiation exposure has health effects. This report describes the rationale and implementation of the Fukushima Health Management Survey.
This cohort study enrolled all people living in Fukushima Prefecture after the earthquake and comprises a basic survey and 4 detailed surveys. The basic survey is to estimate levels of external radiation exposure among all 2.05 million residents. It should be noted that internal radiation levels were estimated by Fukushima Prefecture using whole-body counters. The detailed surveys comprise a thyroid ultrasound examination for all Fukushima children aged 18 years or younger, a comprehensive health check for all residents from the evacuation zones, an assessment of mental health and lifestyles of all residents from the evacuation zones, and recording of all pregnancies and births among all women in the prefecture who were pregnant on 11 March. All data have been entered into a database and will be used to support the residents and analyze the health effects of radiation.
The low response rate (<30%) to the basic survey complicates the estimation of health effects. There have been no cases of malignancy to date among 38 114 children who received thyroid ultrasound examinations. The importance of mental health care was revealed by the mental health and lifestyle survey and the pregnancy and birth survey. This long-term large-scale epidemiologic study is expected to provide valuable data in the investigation of the health effects of low-dose radiation and disaster-related stress.
Preview · Article · Sep 2012 · Journal of Epidemiology
[Show abstract][Hide abstract] ABSTRACT: The Great East Japan Earthquake has occurred on March 11, 2011, in the Tohoku District of Japan. Due to the earthquake, big tsunamis were induced, and they rushed to the Fukushima Nuclear Power Stations, causing severe accidents. Radioactive materials including I-131, Cs-137 and so on were emitted from the plant to the environment. The Japanese government, Fukushima prefectural government and other local governments have struggled against the accidents. The restricted area and deliberate evacuation area are set by the government, and the residents are evacuated. The dose rates in and around Fukushima Prefecture have been monitored by the governments and other involved organizations. Fukushima government has started the health management survey for all residents in Fukushima Prefecture including the questions on their activities for the estimations of their external doses.
No preview · Article · Jun 2012 · The Environmentalist