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Kazaoka Akira,Kumagai Kazuyoshi,Matsushita Junya,Aida Tetsuo,Kuwahara Saki,Aoki Shigeki,Ito Kousei 한국독성학회 2024 Toxicological Research Vol.40 No.2
Several patients with cutaneous adverse drug reactions exhibit extracutaneous organ damages, and it becomes severe in a few patients resulting in death due to multiorgan failure. Understanding the sequential changes in various organs in patients with cutaneous eruption following drug administration will help understand disease onset and progression, aiding the development of prevention strategies and interventions. Therefore, we aimed to understand the effects of abacavir (ABC) on various organs in patients with ABC-induced eruptions by evaluating its effects in a mouse model. We found pathological changes in various organs of HLA-B*57:01 transgenic mice (B*57:01-Tg) following oral administration of ABC (20 mg/ body/day). B*57:01-Tg exhibited a significant body weight decrease from day 1 of ABC administration, and reddening of the auricle was observed from day 5, and approximately 2/3 mice died by day 7. Histopathological examination revealed severe thymic atrophy after day 3, infiltration of inflammatory cells, predominantly lymphocytes with neutrophils, not only in the skin but also in the liver, kidney, and lung after day 5, and an increased number of lymphocytes with enlarged nuclei and granulocytic hematopoiesis were observed in the spleen after day 5. Blood chemistry revealed that albumin/globulin ratio was below 1.0 on day 5, reflecting a systemic inflammatory response, and the aspartate aminotransferase concentration rose to 193 ± 93.0 U/L on day 7, suggesting that cell damage may have occurred in various organs including liver accompanying inflammatory cell infiltration. These examinations of a mouse model of ABC-induced skin eruption show that disorders in various organs other than the skin should be considered and provide insights into the unexpected early systemic responses dependent on HLA-B*57:01.
Structures and Magnetic Properties of Tm1−yYyMn1−xCoxO3
Toshiyuki Tanaka,Akira Kumagai,Yusuke Amakai,Naoki Momono,Shigeyuki Murayama,Hideaki Takano 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.63 No.3
The structure and magnetic properties of Tm1−yYyMn1−xCoxO3 with 0 5 x 5 0.5 and0 5 y 5 0.3 were investigated by X-ray diffraction, specific heat and magnetization measurements. Thulium manganite TmMnO3 prepared by solid-state synthesis at ambient pressure ishexagonal and antiferromagnetic with a N`eel temperature TN of 86 K. The substitution of Y for Tmin TmMnO3 does not greatly affect the fundamental hexagonal structure. The magnetization andspecific heat measurement results for Tm1−yYyMnO3 can be qualitatively explained in terms of thedilution effect of Tm by Y. On the other hand, the structure of TmMn1−xCoxO3 changes graduallyfrom hexagonal to orthorhombic with the substitution of Co for Mn; hexagonal and orthorhombicphases coexist in samples for x 5 0.3 whereas TmMn0.6Co0.4O3 is almost a single orthorhombicphase. The magnetization of TmMn0.6Co0.4O3 in a field of 250 Oe increases rapidly at about60K with decreasing temperature. The difference between zero-field-cooled (ZFC) and field-cooled(FC) magnetizations increases remarkably at about 60 K. Moreover, the temperature dependencesof the ZFC and the FC magnetizations exhibit peaks at about 40 and 30 K, respectively. Thus,TmMn1−xCoxO3 exhibits complex magnetic properties.
Lee, Youngae,Kumagai, Yutaro,Jang, Min Seong,Kim, Jung-Hwan,Yang, Bo-Gie,Lee, Eun-Jung,Kim, You-Me,Akira, Shizuo,Jang, Myoung Ho The American Association of Immunologists, Inc. 2013 JOURNAL OF IMMUNOLOGY Vol.190 No.10
<P>Small intestinal innate lymphoid cells (ILCs) regulate intestinal epithelial cell homeostasis and help to prevent pathogenic bacterial infections by producing IL-22. In a global gene-expression analysis comparing small intestinal ILCs (Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>Sca-1<SUP>−</SUP> cells) with non-ILCs (Lin<SUP>−</SUP>c-Kit<SUP>−</SUP>Sca-1<SUP>−</SUP> cells), we found that Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>Sca-1<SUP>−</SUP> cells highly expressed the mRNAs for Il22, antimicrobial peptides, Csf2rb2 (Il3r), mast cell proteases, and Rorc. We then subdivided the Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>Sca-1<SUP>−</SUP> cells into three groups—Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>NKp46<SUP>−</SUP>CD4<SUP>−</SUP>, Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>NKp46<SUP>−</SUP>CD4<SUP>+</SUP> (CD4<SUP>+</SUP> LTi-like cells), and Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>NKp46<SUP>+</SUP> (NKp46<SUP>+</SUP> ILC22 cells)—and showed that the Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>NKp46<SUP>−</SUP>CD4<SUP>−</SUP> cells produced the highest level of IL-22 protein after IL-1β, IL-23, or IL-1β and IL-23 stimulation. In addition, we showed that the majority of the Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>NKp46<SUP>−</SUP>CD4<SUP>−</SUP> population was IL-7Rα<SUP>+</SUP>CD34<SUP>−</SUP>β7<SUP>int</SUP> cells, and IL-7Rα<SUP>−</SUP> cells could be divided into three subsets (CD34<SUP>+</SUP>β7<SUP>int</SUP>, CD34<SUP>−</SUP>β7<SUP>int</SUP>, and CD34<SUP>int</SUP>β7<SUP>hi</SUP> cells). The IL-7Rα<SUP>+</SUP>CD34<SUP>−</SUP>β7<SUP>int</SUP> cells strongly expressed the transcripts for Il17f and Il22 after costimulation with IL-1β and IL-23. The IL-7Rα<SUP>−</SUP>CD34<SUP>+</SUP>β7<SUP>int</SUP> and IL-7Rα<SUP>−</SUP>CD34<SUP>int</SUP>β7<SUP>hi</SUP> cells predominantly expressed the transcripts for mast cell proteases and differentiated almost entirely into mast cells after 1 wk in culture medium supplemented with a cytokine mixture, whereas the IL-7Rα<SUP>−</SUP>CD34<SUP>−</SUP>β7<SUP>int</SUP> cells highly expressed α-defensins and showed no differentiation. Taken together, these findings indicate that the IL-7Rα<SUP>−</SUP>CD34<SUP>+</SUP>β7<SUP>int</SUP> and IL-7Rα<SUP>−</SUP>CD34<SUP>int</SUP>β7<SUP>hi</SUP> populations are mast cell progenitors, and the IL-7Rα<SUP>+</SUP>CD34<SUP>−</SUP>β7<SUP>int</SUP> (CD4<SUP>−</SUP> LTi-like cells) and IL-7Rα<SUP>−</SUP>CD34<SUP>-</SUP>β7<SUP>int</SUP> populations within Lin<SUP>−</SUP>c-Kit<SUP>+</SUP>NKp46<SUP>−</SUP>CD4<SUP>−</SUP> cells may control intestinal homeostasis and provide intestinal protection by producing high levels of IL-22 and α-defensins, respectively.</P>
Accurate Determination of Childhood Food Allergy Prevalence and Correction of Unnecessary Avoidance
Yuki Okada,Takumi Yamashita,Hideki Kumagai,Yoshihiko Morikawa,Akira Akasawa 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.4
Purpose: Because the true prevalence of food allergy (FA), as based on the results of an oral food challenge test (OFC), is unknown, it is likely that children with suspected FA unnecessarily eliminate potentially causative foods. This study aimed to identify the prevalence of FA and to determine the proportion of children who unnecessarily eliminate food. Methods: To identify children with FA, a primary survey was conducted via a questionnaire with all children aged 0-18 years in Niijima village (remote islands of Japan). In the secondary survey, a detailed medical interview was conducted by doctors with children who currently did not eat some foods. The third survey involved serum food-specific immunoglobulin E (IgE) tests and an OFC for children with suspected FA. Results: Of 376 enrolled children, 374 (99.5%) completed the questionnaire. Some foods were eliminated by 18.6% and 13.0% of all children and those ≥6 years old, respectively. The target population for the secondary survey included 69 children who all completed the medical interview. The target population for the third survey consisted of 35 children, of whom 26 (74.3%) underwent the blood test. An OFC was performed 35 times with 20 children. As a result, the prevalence of FA was 4.9% in children of all ages and 4.7% in those ≥6 years old. Moreover, 55.0% children were able to cease eliminating food intake. Conclusions: It is possible that a considerable number of children unnecessarily eliminate food because of suspected FA.
Tonna Ryutaro,Sasaki Takayuki,Kodama Yuji,Kobayashi Taishi,Akiyama Daisuke,Kirishima Akira,Sato Nobuaki,Kumagai Yuta,Kusaka Ryoji,Watanabe Masayuki 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.4
Simulated debris was synthesized using UO2, Zr, and stainless steel and a heat treatment method under inert or oxidizing conditions. The primary U solid phase of the debris synthesized at 1473 K under inert conditions was UO2, whereas a (U, Zr)O2 solid solution formed at 1873 K. Under oxidizing conditions, a mixture of U3O8 and (Fe, Cr)UO4 phases formed at 1473 K, whereas a (U, Zr)O2+x solid solution formed at 1873 K. The leaching behavior of the fission products from the simulated debris was evaluated using two methods: the irradiation method, for which fission products were produced via neutron irradiation, and the doping method, for which trace amounts of non-radioactive elements were doped into the debris. The dissolution behavior of U depended on the properties of the debris and aqueous solution for immersion. Cs, Sr, and Ba leached out regardless of the primary solid phases. The leaching of high-valence Eu and Ru ions was suppressed, possibly owing to their solid-solution reaction with or incorporation into the uranium compounds of the simulated debris.