薬剤性過敏症症候群(DIHS)の皮疹部においてCD3陽性T細胞数に対するFoxP3陽性制御性T細胞数の割合は増加している

博士（医学）・甲第604号・平成25年11月27日© 2014 British Association of Dermatologists / The definitive version is available at http://onlinelibrary.wiley.com

A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma

Detection of Nε-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells

Nε-(Hexanoyl)lysine, formed by the reaction of lysine with n-6 lipid hydroperoxide, is a lipid peroxidation marker during the initial stage of oxidative stress. The aim of the present study is to indentify Nε-(hexanoyl)lysine-modified proteins in neoplastic transformed gastric mucosal cells by N-methyl-N'-nitro-N-nitrosoguanidine, and to compare the levels of these proteins between gastric mucosal cells and normal gastric cells. Much greater fluorescence of 2-[6-(4'-hydroxy)phenoxyl-3H-xanthen-3-on-9-yl]benzoic acid, an index of the intracellular levels of reactive oxygen species, was observed for gastric mucosal cells compared to normal gastric cells. Nε-(Hexanoyl)lysine-modified proteins were detected by SDS-PAGE or two-dimensional electrophoresis and Western blotting using anti-Nε-(hexanoyl)lysine polyclonal antibody, and a protein band of between 30–40 kDa was clearly increased in gastric mucosal cells compared to normal gastric cells. Two Nε-(hexanoyl)lysine-modified protein spots in gastric mucosal cells were identified as the tropomyosin 1 protein by mass spectrometry using a MASCOT search. The existence of Nε-(hexanoyl)lysine modification in tropomyosin 1 was confirmed by Western blotting of SDS-PAGE-separated or two-dimensional electrophoresis-separated proteins as well as by the immunoprecipitation with anti-tropomyosin 1 antibody. These data indicate that Nε-(hexanoyl)lysine modification of tropomyosin 1 may be related to neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine in gastric epithelial cells

Successful Endoscopic Injection Sclerotherapy of High-Risk Gastroesophageal Varices in a Cirrhotic Patient with Hemophilia A

A 68-year-old man with hemophilia A and liver cirrhosis caused by hepatitis C virus was referred to our hospital to receive prophylactic endoscopic treatment for gastroesophageal varices (GOV). He had large, tense, and winding esophageal varices (EV) with cherry red spots extending down to lesser curve, predicting the likelihood of bleeding. Esophageal endoscopic injection sclerotherapy (EIS) was performed with a total 15 mL of 5% ethanolamine oleate with iopamidol (EOI). Radiographic imaging during EIS demonstrated that 5% EOI reached the afferent vein of the varices. He was administered sufficient factor VIII concentrate before and after EIS to prevent massive bleeding from the varices. Seven days after EIS, upper gastrointestinal endoscopy (UGIE) showed that the varices were eradicated almost completely. Eighteen months after EIS, the varices continued to diminish. We report a successful case of safe and effective EIS for GOV in a high-risk cirrhotic patient with hemophilia A

血清TARC/CCL17値は薬剤性過敏症症候群(DIHS) の早期診断および病勢の指標となりうる。

BACKGROUND:Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. OBJECTIVE:We investigated the pathogenic role of TARC in patients with DIHS. METHODS:Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. RESULTS:Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION:Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.博士（医学）・甲第597号・平成25年3月15日Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved

地域中核病院から病理解剖を依頼したALS

An 82-year-old man, who developed dysphagia several months ago, presented Tokushima University Hospital and was diagnosed of ALS in December 2019. The patient got gradually worse and became bedridden in May 2020. He was admitted into Tokushima University Hospital suffering an aspiration pneumonia in June 2020. The pneumonia rapidly improved with a treatment ; however, the patient failed to be treated at home against his wish and was transferred to Kaminaka Hospital. We accepted his wish for refusing mechanical ventilation or tube feeding. Later, we requested autopsy consent from the patient. He did not refuse our proposal ; therefore, we presearched transporters capable to deceased bodies and contacted the division of pathology in Tokushima University. 60 days later, the patient died due to a suddenly developed putamen hemorrhage. After getting the family's consent, as previously arranged, we transferred the deceased body to Tokushima University and accomplished an autopsy. Although the number of autopsies is declining, we suggest that hospital collaboration may help perform autopsies

Characteristics of the stone monuments in Saijo, Higashi-Hiroshima City, southwest Japan, and their significance for teaching materials of social studies.

本稿の目的は，広島県東広島市旧西条町に分布する石碑の特徴を明らかにすると共に，小学校や中学校社会科の地域学習における石碑の教材的意義を検討することである。調査の結果，202基の石碑が確認され，寺社や公共施設，溜池などに石碑の立地が多くみられた。石碑の建立年との関連を検討すると，第二次世界大戦の終戦を境に，石碑の主な建立目的が地域社会に貢献した人物や行為の顕彰から，寺社への寄附に関連したものへと変化していったことが明らかになった。社会科教材としての意義については，1）学習指導要領への適合と2）石碑の情報量という観点から検討を行い，石碑のもつ教材的意義を3つに分類した。各分類において，具体的な活用方法を考察し想定される学習の展開を提示した。本稿は，「地域学習」の不振の要因のひとつである，地域に即した資料の不足の改善の一助になると期待される。An objective of this study is to clarify the characteristics and distribution of the stone monuments in Saijo, Higashi-Hiroshima City, Hiroshima Prefecture, and discuss their significance for elementary and junior high school social studies teaching materials. Two hundred two monuments were recognized in this area. They were mostly located in temples, shrines, public institutions, roadsides, and irrigation ponds. The purpose of erecting monuments has changed over 150 years from the Meiji era to the present day, which reflects the transition of the history of the local community or local people’s consciousness about their community. All monuments were classified into three levels considering their significance for elementary and junior high school social studies teaching materials: i.e., A. Useful and sufficient information; B. Useful but insufficient information; and C. Others. As a result, we defined 6 monuments as level A, 71 as level B, and 125 as level C. We propose an example of a social studies teaching plan including information about the monuments according to each level. The monuments directly provided information about the history of the local community and the location of historical events; therefore, the teaching plan using information about the monuments has possibility to improve for social studies

Dynamic Interaction between Dislocation and Irradiation-Induced Defects in Stainless Steels during Tensile Deformation

A series of in-situ transmission electron microscopy (TEM) observations during tensile deformation were conducted on the ion-irradiated stainless steel. The jerky motion of dislocations appeared, and dislocations were pinned and depinned at the defects through the in-situ TEM observation. The jump distance traveled by dislocation was measured and discussed as the mean interval of defects interacting with the dislocation motion. Microstructural information of irradiation defects such as obstacle interval was obtained by TEM and atom probe tomography (APT), and the type of pinning site was identified. It was found that Frank loops and black dots were irradiation defects that strongly interacted with dislocations. It was suggested that solute atom clusters act as weak obstacles for dislocations in the dynamic interaction behavior with dislocation motion