Evaluation of the Electronic and Local Structure of Mn in Proton-Conducting Oxide, Ca(Zr,Mn)O3-δ, To Elucidate a Direct Hydrogen-Dissolution Reaction

The protonation mechanism in Mn-doped CaZrO3 (CZM), which involves a direct hydrogen dissolution from the surrounding H2 gas, was investigated by thermogravimetry (TG) and X-ray absorption spectroscopy (XAS). The TG results implied the formation of oxygen vacancies in a H2 atmosphere. The Mn K-edge XAS spectra indicated a reduction of the Mn ions and local structure variations around the Mn ion, but the Zr K-edge spectra were independent of the surrounding atmosphere. The amount of oxygen vacancies was smaller with respect to the reduction of the Mn ions, suggesting direct dissolution of hydrogen. Unlike many typical perovskite-type proton conductors, protonation by direct dissolution of hydrogen and not hydration was the predominant reaction in Mn-doped CaZrO3. Our experimental results demonstrated that the hydration reaction was suppressed because the oxygen vacancy was stable in the distorted ZrO6 symmetry in the CaZrO3 crystal host, whereas protonation proceeded by the direct dissolution of hydrogen stabilizing near the Mn ions in the interstitial sites at the distorted MnO6 octahedron symmetry. The experimental results showed that the structural configurations around dopants play important roles in the stabilization of protons in perovskite-type CZM materials. We demonstrated a new group of proton conductors that can overcome issues with conventional proton conductors by utilizing the direct hydrogen dissolution reaction

長崎国際大学における学生相談活動の現状と課題―カウンセラーと教職員との連携・協働に向けて―

本稿において、学生相談担当カウンセラー（以下、Co）は、学生相談体制の充実化に向けて、長崎国際大学（以下、本学）の学生相談活動を概観した。まず、2018年度の学生相談体制やその利用状況を報告し、2017年度との比較検討を行った。次に、「NIUランチアワー」や「心の健康調査」といった学生相談活動の現状と課題についても検討した。そして、2018年度より、本学に初めて専任化されたCoを活かす視点から、Coと教職員との有効な連携や協働について考察した。その結果、Coは本学の学生の悩みの特徴に応じて、定期的な個別カウンセリングを継続的に提供している可能性がうかがえた。また、心の健康調査の回収率は高く、学生全体への予防的支援の充実化が推察された。一方、学生にとって有益な居場所支援を行ううえでは、場所や人材の確保が課題であると思われた。さらに、Coと教職員の連携や協働では、専任Coがコーディネーターをはじめとする教職員と日頃から情報を共有し学生支援の方針や方法を協議する学生相談体制作りが必要であると考えられた

HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype

ObjectiveAutoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.MethodsHLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.ResultsThe predisposing association of DRB1*04:01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62–5.43), DRB1*04:05 (P = 1.89×10−21, Pc = 5.86×10−20, OR 3.41, 95% CI 2.65–4.38), and DQB1*04:01 (P = 4.66×10−18, Pc = 6.99×10−17, OR 3.89, 95% CI 2.84–5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32–0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10−9, OR 3.52, 95% CI 2.34–5.29). Susceptible diplotypes were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45–424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10−6, OR 10.64, 95% CI 3.19–35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04:05 than without.ConclusionsThe important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQα-β heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes

Differences in Trocar Positioning within the Vertebral Body Using Two Different Positioning Methods: Effect on Trainee Performance

Purpose. To evaluate the educational effect of the Japanese Society of Interventional Radiology 7th Academic Summer Seminar from a technical perspective. Materials and Methods. Nineteen trainees participated in the seminar. The seminar consisted of vertebroplasty trainings using swine with the single-plane landmark method and with the ISOcenter Puncture (ISOP) method. All trainees were advised by an instructor as they operated the instruments and punctured the vertebra. For each trainee, the accuracy in the final position of the needle tip of the initial puncture in each swine training was evaluated. Results. Error in the final position of the needle tip of ≥5 mm from the target puncture site occurred in the lateral direction in 42% (8/19) of trainees with the landmark method and 5% (1/19) with the ISOP method. No error ≥5 mm occurred in the vertical or anteroposterior directions. In terms of puncture accuracy, error in the lateral direction was significantly lower with the ISOP method than with the landmark method (2.2 ± 1.5 mm versus 5.6 ± 3.2 mm). Conclusion. This seminar was effective training for trocar placement for beginners. The puncture was more accurate with the ISOP method than with the landmark method

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011

Use of Cap Analysis Gene Expression to detect human papillomavirus promoter activity patterns at different disease stages

Transcription of human papillomavirus (HPV) genes proceeds unidirectionally from multiple promoters. Direct profiling of transcription start sites (TSSs) by Cap Analysis Gene Expression (CAGE) is a powerful strategy for examining individual HPV promoter activity. The objective of this study was to evaluate alterations of viral promoter activity during infection using CAGE technology. We used CAGE-based sequencing of 46 primary cervical samples, and quantitatively evaluated TSS patterns in the HPV transcriptome at a single-nucleotide resolution. TSS patterns were classified into two types: early promoter-dominant type (Type A) and late promoter-dominant type (Type B). The Type B pattern was more frequently found in CIN1 and CIN2 lesions than in CIN3 and cancer samples. We detected transcriptomes from multiple HPV types in five samples. Interestingly, in each sample, the TSS patterns of both HPV types were the same. The viral gene expression pattern was determined by the differentiation status of the epithelial cells, regardless of HPV type. We performed unbiased analyses of TSSs across the HPV genome in clinical samples. Visualising TSS pattern dynamics, including TSS shifts, provides new insights into how HPV infection status relates to disease state

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed