Perceived risk of nuclear power and other risks during the last 25 years in Japan

The present study described the results of three "fixed-point" surveys on perceived risk related to a list of social and individual risk events during 25 years in Japan. Female clerical staff and researchers were asked to rank 30 items related to various types of technologies and human activities according to their subjective judgments on the order of perceived magnitude of risk in 1983, 1992, and 2007. A similar survey was undertaken for Japanese citizens using web-based questionnaires in 2007. In general, the risk perceptions of the Japanese people, irrespective of gender, age, and occupation, have been uniform during the last 25 years. The female clerical staffs have consistently judged nuclear power as most risky during the last 25 years, whereas researchers' judgment fluctuated with events such as the Chernobyl accident. The ranking of the risk of motor vehicles fell during the 25-y period, whereas those of health risks with food preservatives, x-rays, and antibiotics rose transiently in the 1992 survey. During the 15 years from 1992 to 2007, people tended to learn how to accommodate themselves to these technologies with low risks in exchange for high benefits, except in the case of nuclear power. Nuclear power was regarded as a high-risk item by the Japanese even before the Fukushima nuclear power plant accident in March 2011. This partly explains that the crisis inevitably provokes further high risk perception in Japan, although the overall health threat to the human population in Japan is estimated to be relatively limited so far.     

Subacute oral toxicity study of diethylphthalate based on the draft protocol for “Enhanced OECD Test Guideline no. 407”

We performed a 28-day repeated-dose toxicity study of diethylphthalate based on the draft protocol of the “Enhanced OECD Test Guideline 407” to investigate whether it has endocrine-mediated properties according to this assay. Diethylphthalate was orally administered to SD rats at doses of 0, 40, 200, and 1,000 mg/kg/day for at least 28 days, but no endocrine-mediated effects were detected based on any of the parameters examined, suggesting that diethylphthalate does not possess endocrine properties according to this assay.     

Potential of Reduction in Total Tumor Volume Measured with 3D‐MRI as a Prognostic Factor for Locally‐Advanced Breast Cancer Patients Treated with Primary Chemotherapy

Abstract: For accurate assessment of the response to primary chemotherapy (PCT) for locally advanced breast cancer, we measured reduction in total tumor volume (TTV) by using three‐dimensional magnetic resonance imaging (3D MRI), and examined the relationship between this reduction and patient prognosis. Fifty‐one patients with locally advanced breast cancer were treated with four cycles of docetaxel (60 mg/m²) before surgery. Tumor size was measured with calipers, ultrasonography (US) and conventional two‐dimensional (2D) MRI before and after chemotherapy. TTV was measured with 3D MRI. These and other clinicopathological parameters were statistically analyzed to determine the prognosis for the patients. Median follow‐up time was 46 months (1–64 months). Of the 51 patients, 25 developed distant recurrences. Patients whose TTV decreased by 75% or more after PCT showed significantly better prognosis than others, while tumor size measured with calipers, US and 2D MRI showed no significant relationship with patient prognosis. Of the clinicopathological parameters, only reduction in TTV and histological grade showed a significant association with distant recurrence‐free survival (p = 0.03 and 0.02, log‐rank test), while stepwise multivariate Cox’s proportional hazards analysis identified TTV as the strongest independent prognostic factor. Reduction in TTV measured with 3D MRI can be a useful prognostic factor for patients with locally advanced breast cancer treated with PCT.     

An iso-integral mapping technique using magnetocardiogram, and its possible use for diagnosis of ischemic heart disease

We have developed an iso-integral mapping technique that uses magneto-cardiogram (MCG) data to obtain a map as projected total current image on the torso from the heart. We have also investigated the applicability of iso-integral mapping to the diagnosis of ischemic heart disease. We simulated and measured the characteristics of two types of iso-integral maps: one using tangential (B _xy ) components, and one using the normal component (B _z ). Each vector component was measured by two types of superconducting quantum interference device (SQUID) system to determine the tangential and normal components. The tangential component of the magnetic field appeared to be equivalent to the current image in the myocardium projected on the observing plane, and we were able to obtain a projected total current image by integration of the tangential components during the depolarization and repolarization processes. And we found that the iso-integral maps of normal hearts showed similar pattern in both processes; however, those of ischemic hearts showed different patterns.     

RAF1–MEK/ERK pathway-dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation

Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogen-activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF–MAPK pathway and Wnt/β-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS–MAPK pathway and Wnt/β-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1–MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1–ARL4C and BRAFV600E–MEK/ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1–MEK/ERK–ARL4C axis, which may function in cooperation with the BRAFV600E–MEK/ERK pathway, promotes ameloblastoma development. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Further development of the rat Pig-a mutation assay: measuring rat Pig-a mutant bone marrow erythroids and a high throughput assay for mutant peripheral blood reticulocytes

Recent studies indicate that the Pig-a assay is a promising tool for evaluating in vivo mutagenicity. We have developed novel rat Pig-a assays that facilitate measuring mutant frequencies in two early arising populations of blood cells, bone marrow erythroids (BMEs) and peripheral blood (PB) reticulocytes (RETs). In these assays, bone marrow cells of erythroid origin and PB red blood cells (RBCs) were identified using an antibody against rat erythroid-specific marker HIS49. In addition, RETs were selectivity enriched from PB using magnetic separation of cells positive for CD71, a transferrin receptor expressed on the surface of BMEs and RETs, but not on the surface of mature RBCs. With magnetic enrichment, more than 1 x 10(6) CD71-positive RETs could be evaluated by flow cytometry for Pig-a mutant frequency within 5 to 8 min. CD59-deficient RET and BME frequencies of more than 100 x 10(-6) and 80 x 10(-6) were detected 1 week after treating rats with 40 mg/kg N-ethyl-N-nitrosourea; by comparison, the frequency of CD59-deficient total RBCs in these rats was 13.2 x 10(-6). The frequency of spontaneous Pig-a mutant RETs and BMEs was less than 5 x 10(-6) and 15 x 10(-6), respectively. Since approximately 98% of nucleated cells in the BME fraction were erythroblasts, it should be possible to use BMEs to determine the spectrum of CD59-deficient Pig-a mutations in cells of erythroid lineage. Conducting concurrent Pig-a assays on RETs and BMEs may be useful for evaluating the in vivo mutagenicity of chemicals, especially when prolonged mutant manifestation is not feasible or when the confirmation of mutation induction is necessary.     

Positron emission tomography for predicting malignancy of sinonasal inverted papilloma

BACKGROUND: Sinonasal inverted papilloma (IP) is an uncommon nasal tumor. It is known for being locally invasive and recurrent, with a high probability of malignant transformation. Accurate initial staging and close surveillance are critical in the management of the disease. METHODS AND RESULTS: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) was performed in 5 patients with IP. High FDG uptake (maximum standardized uptake (SUVmax) value >3.0) was observed in all patients, and 2 patients with IP associated with squamous cell carcinoma (SCC) exhibited higher SUVmax values. CONCLUSION: The SUVmax value of a sinonasal tumor can warn the surgeon of the probability of an associated malignancy, even when preoperative biopsy demonstrates a purely benign papilloma.