頚動脈プラークにおいてS100A4発現が亢進し、陽性リモデリングと関連する

京都大学新制・論文博士博士(医学)乙第13515号論医博第2265号新制||医||1061(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 湊谷 謙司, 教授 石見 拓, 教授 江木 盛時学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Inconsistency in the Standard of Care–Toward Evidence-Based Management of Exertional Heat Stroke

Tokyo 2020 Summer Olympics are projected to experience environmental heat stress that surpasses the environmental conditions observed in the Atlanta (1996), Athens (2004), Beijing (2008), and Rio (2016) Summer Olympics. This raises particular concerns for athletes who will likely to be exposed to extreme heat during the competitions. Therefore, in mass-participation event during warm season, it is vital for the hosting organization to build preparedness and resilience against heat, including appropriate treatment, and management strategies for exertional heat stroke (EHS). However, despite the existing literature regarding the evidence-based management of EHS, rectal thermometry and whole-body cold-water immersion are not readily accepted by medical professionals outside of the sports, and military medicine professionals. Current Japanese medical standard is no exception in falling behind on evidence-based management of EHS. Therefore, the first aim of this paper is to elucidate the inconsistency between the standard of care provided in Japan for EHS and what has been accepted as the gold standard by the scientific literature. The second aim of this paper is to provide optimal EHS management strategies that should be implemented at the Tokyo 2020 Summer Olympics from organizational level to maximize the safety of athletes and to improve organizational resilience to heat. The risk of extreme heat is often neglected until a catastrophic incidence occurs. It is vital for the Japanese medical leadership and athletic communities to re-examine the current EHS management strategies and implement evidence-based countermeasure for EHS to expand the application of scientific knowledge

Irradiation Accelerates Plaque Formation and Cellular Senescence in Flow‐Altered Carotid Arteries of Apolipoprotein E Knock‐Out Mice

[Background] Chronic inflammation through cellular senescence, known as the senescence‐associated secretory phenotype, is a mechanism of various organ diseases, including atherosclerosis. Particularly, ionizing radiation (IR) contributes to cellular senescence by causing DNA damage. Although previous clinical studies have demonstrated that radiotherapy causes atherosclerosis as a long‐term side effect, the detailed mechanism is unclear. This study was conducted to investigate the relationship between radiation‐induced atherosclerosis and senescence‐associated secretory phenotype in murine carotid arteries. [Methods and Results] Partial ligation of the left carotid artery branches in 9‐week‐old male apolipoprotein E‐deficient mice was performed to induce atherosclerosis. The mice received total body irradiation at a dose of 6 Gy using gamma rays at 2 weeks post operation. We compared the samples collected 4 weeks after IR with unirradiated control samples. The IR and control groups presented pathologically progressive lesions in 90.9% and 72.3% of mice, respectively. Plaque volume, macrophage accumulation, and phenotype switching of vascular smooth muscle cells were advanced in the IR group. Irradiated samples showed increased persistent DNA damage response (53BP1 [p53 binding protein 1]), upregulated cyclin‐dependent kinase inhibitors (p16INK4a and p21), and elevated inflammatory chemokines expression (monocyte chemotactic protein‐1, keratinocyte‐derived chemokine, and macrophage inflammatory protein 2). [Conclusions] IR promoted plaque growth in murine carotid arteries. Our findings support the possibility that senescence‐associated secretory phenotype aggravates atherogenesis in irradiated artery. This mice model might contribute to mechanism elucidation of radiation‐induced atherosclerosis

Experimental Research on Performances of Air Turbines for a Fixed Oscillating Water Column-Type Wave Energy Converter

A fixed oscillating water column (OWC)-type wave energy converter is composed of an air chamber for primary conversion and an air turbine for secondary conversion. In the optimal design method of a fixed OWC-type wave energy converter, it is necessary to develop a design method which can consider the characteristics of incident wave motion, the motion of the internal free surface affected in the structure such as a partly submerged wall, the fluctuation of air pressure in an air chamber, the rotation of the air turbine. In this paper, the 2-dimensional wave tank tests in regular waves for the performance evaluation of the air turbines in a fixed OWC-type wave energy converter were conducted to obtain the data needed to make this design method. As the results, the effects of the impulse turbine specification such as the rotor inlet/outlet angle, the guide vane's number and the vane's setting angle on the primary and secondary conversion efficiencies are clarified experimentally. Furthermore, the performances of the Wells turbines with different number of blade are presented for comparison of the operating condition

Transcriptional Repression of Cdc25B by IER5 Inhibits the Proliferation of Leukemic Progenitor Cells through NF-YB and p300 in Acute Myeloid Leukemia

The immediately-early response gene 5 (IER5) has been reported to be induced by γ-ray irradiation and to play a role in the induction of cell death caused by radiation. We previously identified IER5 as one of the 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (TMPP)-induced transcriptional responses in AML cells, using microarrays that encompassed the entire human genome. However, the biochemical pathway and mechanisms of IER5 function in regulation of the cell cycle remain unclear. In this study, we investigated the involvement of IER5 in the cell cycle and in cell proliferation of acute myeloid leukemia (AML) cells. We found that the over-expression of IER5 in AML cell lines and in AML-derived ALDHhi (High Aldehyde Dehydrogenase activity)/CD34+ cells inhibited their proliferation compared to control cells, through induction of G2/M cell cycle arrest and a decrease in Cdc25B expression. Moreover, the over-expression of IER5 reduced colony formation of AML-derived ALDHhi/CD34+ cells due to a decrease in Cdc25B expression. In addition, over-expression of Cdc25B restored TMPP inhibitory effects on colony formation in IER5-suppressed AML-derived ALDHhi/CD34+ cells. Furthermore, the IER5 reduced Cdc25B mRNA expression through direct binding to Cdc25B promoter and mediated its transcriptional attenuation through NF-YB and p300 transcriptinal factors. In summary, we found that transcriptional repression mediated by IER5 regulates Cdc25B expression levels via the release of NF-YB and p300 in AML-derived ALDHhi/CD34+ cells, resulting in inhibition of AML progenitor cell proliferation through modulation of cell cycle. Thus, the induction of IER5 expression represents an attractive target for AML therapy

Genome‐wide SNP genotyping reveals hidden population structure of an acroporid species at a subtropical coral island: Implications for coral restoration

1. It is essential to consider genetic composition for both conventional coral restoration management and for initiating new interventions to counter the significant global decline in living corals. Population genetic structure at a fine spatial scale should be carefully evaluated before implementing strategies to achieve self-sustaining ecosystems via coral restoration. 2. This study investigated the population genetic structure of two acroporid species at Kume Island, Okinawa, Japan. There were 140 colonies of Acropora digitifera collected from seven study sites, and 81 colonies of Acropora tenuis from six sites. In total, 384 single nucleotide polymorphism (SNP) loci for A. digitifera and 470 SNPs for A. tenuis were obtained using a comparatively economical technique, Multiplexed ISSR Genotyping by sequencing. 3. Observed heterozygosity was significantly lower than expected heterozygosity at all SNP sites in both acroporid species, suggesting deficient genetic diversity possibly caused by past massive coral bleaching. Even though both species are broadcast spawners, the population structure was different in the two species. No detectable structure was evident in A. digitifera, but two distinct clades were found in A. tenuis. The genetic homogeneity of A. digitifera at Kume Island suggests that this species could be used as a focal species for active restoration in terms of genetic differentiation at this island. By contrast, A. tenuis unexpectedly included two distinct clades with little or no admixture within a small study area, possibly representing two reproductively isolated cryptic species. Thus, when using A. tenuis, it would be prudent to avoid disturbing the genetic composition of wild populations until this question is answered.journal articl

Development of a novel artificial intelligence algorithm to detect pulmonary nodules on chest radiography

Background: In this study, we aimed to develop a novel artificial intelligence (AI) algorithm to support pulmonary nodule detection, which will enable physicians to efficiently interpret chest radiographs for lung cancer diagnosis. Methods: We analyzed chest X-ray images obtained from a health examination center in Fukushima and the National Institutes of Health (NIH) Chest X-ray 14 dataset. We categorized these data into two types: type A included both Fukushima and NIH datasets, and type B included only the Fukushima dataset. We also demonstrated pulmonary nodules in the form of a heatmap display on each chest radiograph and calculated the positive probability score as an index value. Results: Our novel AI algorithms had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.74, a sensitivity of 0.75, and a specificity of 0.60 for the type A dataset. For the type B dataset, the respective values were 0.79, 0.72, and 0.74. The algorithms in both the type A and B datasets were superior to the accuracy of radiologists and similar to previous studies. Conclusions: The proprietary AI algorithms had a similar accuracy for interpreting chest radiographs when compared with previous studies and radiologists. Especially, we could train a high quality AI algorithm, even with our small type B data set. However, further studies are needed to improve and further validate the accuracy of our AI algorithm

Social robot for older adults with cognitive decline: a preliminary trial

The number of older adults living alone is rapidly increasing. Loneliness in older adults not only degrade their quality of life but also causes troubles such as heavy burden on the medical staff, especially when cognitive decline is present. Social robots could be used in several ways to reduce such problems. As a first step towards this goal, we introduced conversation robots into the homes of older adults with cognitive decline to evaluate the robot’s availability and acceptance during several months. The study involved two steps, one for evaluating the robustness of the proposed robotic system, and the second one to examine the long-term acceptance of social robots by older adults with cognitive decline living alone. Our data shows that after several weeks of human-robot interaction, the participants continued to use the robot and successfully integrated them into their lives. These results open the possibility of further research involving how sustained interaction can be achieved, as well as which factors contributed to the acceptance of the robot