Sparing and enhancing dose protraction effects for radiation damage to the aorta of wild-type mice.

PURPOSE: Our previous work indicated the greater magnitude of damage to the thoracic aorta at 6 months after starting 5 Gy irradiation in descending order of exposure to X-rays in 25 fractions > acute X-rays > acute γ-rays > X-rays in 100 fractions ≫ chronic γ-rays, in which the limitations of the study included a lack of data for fractionated γ-ray exposure. To better understand effects of dose protraction and radiation quality, the present study examined changes after exposure to γ-rays in 25 fractions, and compared its biological effectiveness with five other irradiation regimens. MATERIALS AND METHODS: Male C57BL/6J mice received 5 Gy of 137Cs γ-rays delivered in 25 fractions spread over six weeks. At 6 months after starting irradiation, mice were subjected to echocardiography, followed by tissue sampling. The descending thoracic aorta underwent scanning electron microscopy, immunofluorescence staining and histochemical staining. The integrative analysis of multiple aortic endpoints was conducted for inter-regimen comparisons. RESULTS: Exposure to γ-rays in 25 fractions induced vascular damage (evidenced by increases in endothelial detachment and vascular endothelial cell death, decreases in endothelial waviness, CD31, endothelial nitric oxide synthase and vascular endothelial cadherin), inflammation (evidenced by increases in tumor necrosis factor α, CD68 and F4/80) and fibrosis (evidenced by increases in transforming growth factor ß1, alanine blue stain and intima-media thickness). The integrative analysis revealed biological effectiveness in descending order of exposure to X-rays in 25 fractions > acute X-rays > γ-rays in 25 fractions > acute γ-rays > X-rays in 100 fractions ≫ chronic γ-rays. CONCLUSIONS: The results suggest that dose protraction effects on aortic damage depend on radiation quality, and are not a simple function of dose rate and the number of fractions.

Thyroid cancer risk after radiation exposure in adults-systematic review and meta-analysis.

Notably, the growing use of radionuclear technology, especially in diagnostic and therapeutic procedures involving radiation exposure, raises concerns about the health effects of radiation. Although epidemiological studies have provided strong evidence for elevated thyroid cancer risk after radiation exposure in childhood, the risk of thyroid cancer associated with adult exposure remains to be investigated. We conducted a systematic review and meta-analysis of relevant studies on the risk of developing thyroid cancer after radiation exposure in adulthood. The PubMed and Web of Science databases were used to select eligible articles. After screening, a total of 15 studies were identified in which estimates of the standardized incidence ratio (SIR) and the relative risk (RR) of thyroid cancer were available in 8 and 11 studies, respectively. The overall SIR estimated by the random effects model was 2.19 [95% confidence interval (CI), 1.54, 3.10]. Cochran's Q test showed significant heterogeneity in the SIRs (Q = 178, P < 0.0001). The overall RR at 10 mGy was 1.0038 (95% CI, 0.9991, 1.0085), with no significant heterogeneity (Q = 9.30, P = 0.5041). The total SIR, as well as that from each study, indicated a statistically significant excess, which could be related to screening bias. Radiation-related thyroid cancer risk was elevated in a few studies; however, the overall estimate of the RR at 10 mGy was not significant. This study demonstrates no strong epidemiological evidence for the risk of thyroid cancer in radiation exposure during adulthood; however, further research is needed.

Interlaboratory comparison of electron paramagnetic resonance tooth enamel dosimetry with investigations of the dose responses of the standard samples.

A total of seven Japanese laboratories participated in an intercomparison study to estimate the dose given to tooth enamel samples, using the electron spin resonance method. Each of four of the participating laboratories prepared a set of tooth enamel samples, using the electron spin resonance method. Four of the participating laboratories each prepared a set of tooth enamel samples, consisting of seven standard aliquots irradiated from 100 to 2000 mGy and three samples with an 'unknown' dose between 140 and 960 mGy, were intended to eliminate bias from sample preparation. Although not all seven laboratories measured all four sets of samples, the major finding was that systematic biases in estimating doses may be caused by differences in laboratory measurements rather than by the enamel extracting procedures. When doses were averaged by measurements made by multiple laboratories, the averaged values were close to the actual values. Scattering in the intercepts in the standard dose response would be a serious problem in actual dosimetry where no background sample is available.

Effect of exposure to radiation caused by an atomic bomb on endothelial function in atomic bomb survivors.

Background: The purpose of this study was to evaluate the effects of exposure to radiation caused by an atomic bomb in atomic bomb survivors on vascular function and vascular structure and to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure in atomic bomb survivors. Methods: Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as indices of vascular function, brachial-ankle pulse wave velocity (baPWV) as an index of vascular function and vascular structure, and brachial artery intima-media thickness (IMT) as an index of vascular structure were measured in 131 atomic bomb survivors and 1,153 control subjects who were not exposed to the atomic bomb. Ten of the 131 atomic bomb survivors with estimated radiation dose in a cohort study of Atomic Bomb Survivors in Hiroshima were enrolled in the study to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure. Results: There was no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. After adjustment of confounding factors, there was still no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb was negatively correlated with FMD (ρ = -0.73, P = 0.02), whereas radiation dose was not correlated with NID, baPWV or brachial artery IMT. Conclusion: There were no significant differences in vascular function and vascular structure between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb might be negatively correlated with endothelial function.

[Relationship between radiation knowledge and radiation effect anxiety on the next generation: An analysis of a questionnaire survey disseminated to residents in Fukushima Prefecture].

Objectives　Since the Fukushima Daiichi Nuclear Power Plant accident caused by the Great East Japan Earthquake, many people in Fukushima Prefecture have been concerned about the effects of radiation on their offspring. Although this fear should be relieved since no epidemiological study has shown evidential cases, situations wherein some people misunderstood the existence of evidence have been independently reported. Therefore, in this study, we examined the relationship between radiation knowledge and anxiety about radiation-based genetic effects using a survey mailed to residents in Fukushima Prefecture.Methods　In August 2016, we attempted to contact 2,000 people aged 20 to 79 years in Fukushima Prefecture through a survey distributed by mail inquiring about residents' health. We received 861 responses. Respondents selected their level of concern about radiation effects on the next generation on a four-point scale and answered five knowledge questions about radiation effects and protection. Responses were "correct," "incorrect," or "not sure." After adjusting according to residential area, family configuration, age, sex, academic background, media used, and trusted information source, we conducted multiple regression analyses to investigate the relationship between the level of concern and answers to the knowledge questions.Results　People who answered the knowledge questions more correctly had lower levels of anxiety. The number of "not sure" responses was unrelated to anxiety level. The results indicated that correct answers to questions related to radiation residuals in the body and genetic effects were negatively associated with anxiety. Incorrect answers to the question about genetic effects and another related to cell repair systems were positively associated with anxiety. Moreover, while a correct answer to another question related to the linear threshold model had a positive association, the association was insignificant. Further, any response related to radiation reference values in foods showed no association.Conclusion　Based on these results, we observed an association between the number of respondents with a correct knowledge of radiation and the degree of anxiety about radiation effects on the next generation. However, this relationship and its strength varied depending on the specific knowledge content. As a limitation of this study, the study could not establish any causality. Further studies, such as prospective interventional studies, should be conducted.

Behavior of the electron spin resonance signals in X-ray irradiated human fingernails for the establishment of a dose reconstruction procedure.

The retrospective dosimetry that follows accidental X-ray exposure is becoming more significant for improving radiation diagnosis and treatment. We investigated the dosimetric properties of electron spin resonance (ESR) signals in X-ray irradiated fingernails under conditions that resemble realistic situations. We collected fingernails from 12 Japanese donors between the ages of 30 to 70. The sampled fingernails were utilized for X-ray irradiation, mechanical stimulation and background measurements. We also collected 10 toenails from one of the donors to evaluate their differences from fingernails. Additionally, we prepared 15 samples from two donors to compare the signals generated by γ-rays to those by X-rays. After observing the linear dose-response for both X- and γ-ray irradiated samples, we found that the sensitivity of the air-absorbed dose of γ-ray irradiated samples was identical to that of X-ray irradiated samples. The effect from secondary electrons seemed to be small in fingernails. The inter-individual variation in the sensitivity was no greater than the intra-individual variation. The signal intensities in each measurement fluctuated about the linear response curve, and the size of the fluctuation was dependent on the sample. The average fluctuation corresponded to 1.7 Gy, and the standard deviation was 1.3 Gy. The signal induced by X-rays could be erased by soaking the samples in water and subsequently drying them for four days, which allowed us to estimate the signal intensity prior to the exposure. These characteristics of the ESR signal induced by X-rays facilitate the development of a feasible protocol for fingernail dose reconstruction.

Prospects and status of the dosimetry system for atomic bomb survivor cohort study conducted at Research Institute for Radiation Biology and Medicine of Hiroshima University.

The Research Institute for Radiation Biology and Medicine (RIRBM) of Hiroshima University has been conducting a cohort study of atomic bomb survivors (ABS). Cohort members include those who were issued an Atomic Bomb Health Handbook from the Hiroshima local government. A series of dosimetry systems for the ABS were developed at RIRBM to evaluate the health effects associated with radiation exposure. The framework used to estimate individual doses in our dosimetry systems for ABS is mainly based on the Dosimetry System 86, and its revisions developed by the Radiation Effect Research Foundation. This article describes the design and computational principles for the dosimetry systems in RIRBM and the history of the revisions, from the first version of the system, ABS93D, to the most recent version, ABS16D. We then provide a perspective for further improvement and application of the dosimetry system.

Imaging Cherenkov emission for quality assurance of high-dose-rate brachytherapy.

With advances in high-dose-rate (HDR) brachytherapy, the importance of quality assurance (QA) is increasing to ensure safe delivery of the treatment by measuring dose distribution and positioning the source with much closer intervals for highly active sources. However, conventional QA is time-consuming, involving the use of several different measurement tools. Here, we developed simple QA method for HDR brachytherapy based on the imaging of Cherenkov emission and evaluated its performance. Light emission from pure water irradiated by an 192Ir γ-ray source was captured using a charge-coupled device camera. Monte Carlo calculations showed that the observed light was primarily Cherenkov emissions produced by Compton-scattered electrons from the γ-rays. The uncorrected Cherenkov light distribution, which was 5% on average except near the source (within 7 mm from the centre), agreed with the dose distribution calculated using the treatment planning system. The accuracy was attributed to isotropic radiation and short-range Compton electrons. The source positional interval, as measured from the light images, was comparable to the expected intervals, yielding spatial resolution similar to that permitted by conventional film measurements. The method should be highly suitable for quick and easy QA investigations of HDR brachytherapy as it allows simultaneous measurements of dose distribution, source strength, and source position using a single image.

Usefulness of combining 123I-FP-CIT-SPECT striatal asymmetry index and cardiac 123I-metaiodobenzylguanidine scintigraphy examinations for diagnosis of parkinsonisms.

BACKGROUND: Although single-photon emission computerized tomography of the dopamine transporter (DAT-SPECT) is useful for diagnosing parkinsonian syndrome, its applicability toward the early phase of Parkinson's disease remains unknown. METHODS: We enrolled 32 patients showing parkinsonism with normal cardiac 123I-metaiodobenzylguanidine (MIBG) uptake and abnormal DAT-SPECT findings among 84 consecutive patients with parkinsonism. We divided these patients into two groups (group 1: Parkinson's disease, group 2: corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy), and compared their clinical characteristics, specific binding ratios, and striatal asymmetry indexes on DAT-SPECT examinations. RESULTS: The striatal asymmetry indexes were significantly lower in group 1 than in group 2 (p<0.05), but there were no differences in the specific binding ratios between the two groups. CONCLUSION: The combined use of striatal asymmetry index on DAT-SPECT and cardiac MIBG scintigraphy might offer useful clues for the differential diagnosis of the early phase Parkinson's disease from other parkinsonian syndromes.

Differentiation of cancer from atrial fibrillation in patients with acute multifocal stroke.

OBJECTIVE: Acute multifocal embolic infarction (AMEI) is conventionally caused by etiologies such as cardioembolism due to atrial fibrillation (Af), but can also be caused by serious underlying diseases such as cancer. We characterized cancer-related AMEI and identified useful indicators for cancer-associated strokes. METHODS: A retrospective analysis was performed on 35 patients with Af-related AMEI and 35 patients with cancer-related AMEI selected from 1235 consecutive patients with acute infarcts. All patients received diffusion-weighted magnetic resonance (MR) imaging. Cerebral MR angiography, carotid and cardiac ultrasonography, electrocardiogram-monitoring and whole body computed tomography were also performed on these patients. D-dimer levels were evaluated on admission, and were measured during the sub-acute phase in 19 of the patients with Af and 27 of the patients with cancer. RESULTS: Acute phase D-dimer levels were significantly higher in patients with cancer than in patients with Af alone. The cut-off D-dimer value to identify cancer-associated infarcts was 2.0µg/mL. D-dimer levels during the sub-acute phase remained elevated in the cancer patients. CONCLUSIONS: We may differentiate cancer-associated AMEI from Af using a D-dimer level≥2.0µg/mL, which does not decrease during the sub-acute phase.

Retrospective analysis of parkinsonian patients exhibiting normal (123)I-MIBG cardiac uptake.

BACKGROUND: Although most patients with Parkinson's disease (PD) show decreased cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, some exhibit normal uptake. We evaluated the clinical characteristics of such patients. METHODS: We enrolled 154 non-demented patients showing parkinsonism with normal cardiac MIBG uptake and had been clinically followed up during 29.9 ± 27.6 months. We defined the patients who did not fit the exclusion criteria for PD and demonstrated ≥ 30% reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score after anti-Parkinson agent administration as probable PD. We compared clinical characteristics and the cardiac MIBG heart-to-mediastinum (H/M) ratio between the probable PD group (N=37) and other groups (N=117). RESULTS: The probable PD group showed significantly higher UPDRS motor scores and greater incidence of tremor/rigidity than those of other groups. In addition, they showed a significantly lower cardiac MIBG H/M ratio in the delayed phase (delayed, p<0.0001). Washout-rate (WR) was significantly higher in probable PD cases (p<0.0001). Among 16 probable PD patients undergoing serial cardiac MIBG scintigraphy, the delayed phase cardiac MIBG H/M ratio showed a significant decrease and WR significantly increased during follow-up periods. CONCLUSIONS: An increase in WR and lower delayed phase cardiac MIBG uptake were found to be characteristics of such patients.

Histone deacetylase inhibitor attenuates neurotoxicity of clioquinol in PC12 cells.

Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells.

Voriconazole-responsive disseminated nodular lesions on spinal MRI.

A 74-year-old woman was hospitalized due to dysuria, weakness and dysesthesia of the lower extremities. She was in an immunosuppressed state following the administration of methylprednisolone therapy for idiopathic interstitial pneumonia. Cerebrospinal fluid and blood cultures were negative, and no infectious biomarkers were found. A gadolinium (Gd)-enhanced T1-weighted image of magnetic resonance imaging (MRI) revealed disseminated nodular lesions along the spinal cord. We suspected a diagnosis of seronegative deep mycosis and initiated anti-fungal therapy with voriconazole, which subsequently alleviated all of the patient's symptoms and MRI findings. Therefore, the presence of Gd-enhanced disseminated nodules on spinal MRI may be a good marker of deep meningeal mycosis.

Targeting of aquaporin 4 into lipid rafts and its biological significance.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is considered to be caused by the binding of NMO-IgG to aquaporin 4 (AQP4) on astrocytes, which initiates complement-dependent cytotoxicity. AQP4 has two isoforms, i.e., M1 and M23. AQP4 is considered to form heterotetramers containing both isoforms in vivo. Most of the previous studies were performed using either one of the isoforms expressing cell lines. In this study, we generated a fluorescent epitope-tagged AQP4 M1 and M23 co-expressing astrocyte cell line and examined the subcellular targeting of AQP4. In this cell line, AQP4 was targeted mostly to membrane lipid rafts fraction evidenced by sucrose density gradient ultracentrifugation followed by Western blotting with anti-AQP4 antibody. Cholesterol depletion with methyl-ß-cyclodextrin or simvastatin resulted in the dislocation (relocation) of AQP4 from lipid rafts to non-rafts fraction of the membrane and AQP4 was not internalized intracellularly. This change in the localization of AQP4 on membrane significantly reduced complement-dependent cytotoxic effects of NMO-IgG obtained from patients with NMO without affecting AQP4 orthogonal arrays. Thus, these data strongly suggest that the targeting of AQP4 in the lipid rafts is closely related to the pathogenic effects of NMO-IgG.