Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas.
The Fukushima Health Management Survey (FHMS) was established in response to the Fukushima Daiichi Nuclear Power Plant accident on March 11, 2011. The primary objectives of the study are to monitor residents’ long-term health and promote their future well-being, and to determine the health effects of long-term low-dose radiation exposure. This special issue summarizes the results and current status of the FHMS and discusses the challenges and future directions of the FHMS. The FHMS, a cohort study of all people who were residents in Fukushima Prefecture at the time of the accident, consists of a Basic Survey, Thyroid Ultrasound Examination, Comprehensive Health Check, Mental Health and Lifestyle Survey, and Pregnancy and Birth Survey. The radiation exposure was estimated based on the behavioral records examined using the Basic Survey. Although the response rate was low in the Basic Survey, the representativeness of the radiation exposure data was confirmed using additional surveys. There appears to be no relationship between the radiation exposure and risk of thyroid cancer, although more thyroid cancer cases were detected than initially expected. The ongoing Comprehensive Health Check and Mental Health and Lifestyle Survey have provided evidence of worsening physical and mental health status. The Pregnancy and Birth Survey showed rates of preterm delivery, low birth weight, and congenital abnormalities similar to the national average. Considering the above evidence, the Fukushima Prefectural Government decided to end the Pregnancy and Birth Survey at the end of March 2021, as recommended by the Prefectural Oversight Committee. The framework of the FHMS has not changed, but the FHMS needs to adapt according to the survey results and the changing needs of the eligible residents and municipalities.
Excess risk of leukemia and brain tumors after CT scans in children has been reported. We performed dicentric chromosome assay (DCAs) before and after CT scan to assess effects of low-dose ionizing radiation on chromosomes. Peripheral blood (PB) lymphocytes were collected from 10 patients before and after a CT scan. DCA was performed by analyzing either 1,000 or 2,000 metaphases using both Giemsa staining and centromere-fluorescence in situ hybridization (Centromere-FISH). The increment of DIC formation was compared with effective radiation dose calculated using the computational dosimetry system, WAZA-ARI and dose length product (DLP) in a CT scan. Dicentric chromosome (DIC) formation increased significantly after a single CT scan and increased DIC formation was found in all patients. A good correlation between the increment of DIC formation determined by analysis of 2,000 metaphases using Giemsa staining and those by 2,000 metaphases using Centromere-FISH was observed. However, no correlation was observed between the increment of DIC formation and the effective radiation dose. Therefore, these results suggest that chromosome cleavage may be induced by one CT scan and we recommend 2,000 or more metaphases be analyzed in Giemsa staining or Centromere-FISH for DCAs in cases of low-dose radiation exposure.
In terms of biological dosimetry at the time of radiation exposure, the dicentric chromosome (Dic) assay (DCA) is the gold standard for assessing for the acute phase and chromosome translocation (Tr) analysis is the gold standard for assessing the chronic phase. It is desirable to have individual dose–response curves (DRCs) for each laboratory because the analysis criteria differ between laboratories. We constructed the DRCs for radiation dose estimation (with three methods) using peripheral blood (PB) samples from five healthy individuals. Aliquots were irradiated with one of eight gamma-ray doses (0, 10, 20, 50, 100, 200, 500 or 1000 mGy), then cultured for 48 h. The number of chromosome aberrations (CAs) was analyzed by DCA, using Giemsa staining and centromere-fluorescence in situ hybridization (centromere-FISH) and by chromosome painting (chromosome pairs 1, 2 and 4) for Tr analysis. In DCA, there was large variation between individuals in the frequency of Dics formed, and the slopes of the DRCs were different. In Tr analysis, although variation was observed in the frequency of Tr, the slopes of the DRCs were similar after adjusting the background for age. Good correlation between the irradiation dose and the frequency of CAs formed was observed with these three DRCs. However, performing three different biological dosimetry assays simultaneously on PB from five donors nonetheless results in variation in the frequency of CAs formed, especially at doses of 50 mGy or less, highlighting the difficulty of biological dosimetry using these methods. We conclude that it might be difficult to construct universal DRCs.
Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011–2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011–2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008–2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011–2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.
The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced people to evacuate their hometowns. Many evacuees from the government-designated evacuation zone were forced to change their lifestyle, diet, exercise, and other personal habits. The Comprehensive Health Check (CHC), 1 of 4 detailed surveys of The Fukushima Health Management Survey (FHMS), was implemented to support the prevention of lifestyle-related disease. The aim of this study was to analyze changes in red blood cell count (RBC), hemoglobin (Hb) levels, and hematocrit (Ht) levels by comparing data from the medical health checkup before and after the disaster in individuals who were 40 years old or older. Subjects in this study were Japanese men and women living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima prefecture. Annual health checkups with a focus on metabolic syndrome for insured persons/dependents aged 40 or older by Health Care Insurers have been conducted since 2008. All analyses in this study were limited to men and women aged 40–90 years. Changes in RBC, Hb levels, Ht levels, and prevalence of polycythemia before and after the disaster were compared. First, RBC, Hb, and Ht significantly increased in both men and women evacuees. The evacuation was significantly associated with increased Hb levels after adjustment for age, gender, smoking status, excess ethanol intake, BMI, and baseline Hb level (β = 0.16, p < 0.001). Furthermore, the prevalence of polycythemia stratified by smoking status or obesity also increased in the evacuee group. To our knowledge, this is the first report revealing that the evacuation was associated with the risk of polycythemia. This information could be very important for periodic health checkup and lifestyle recommendations for evacuees in the future.