胸腺ネガティブ選択においてTCRシグナルをアポトーシスに導くエンハンサーの同定と解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 内丸 薫, 東京大学教授 黒田 真也, 東京大学教授 鈴木 穣, 東京大学准教授 程 久美子, 東北大学准教授 山下 理宇University of Tokyo(東京大学

Simultaneous in-situ multi-element analysis of minerals on thin section using LA-ICP-MS

Department of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityIn-situ trace-element analyses on minerals are especially useful for characterization of geological materials. We explored optimistic conditions of a inductively coupled plasma mass spectroscopy with laser-ablation sample introduction method (LA-ICP-MS) for in-situ quantitative trace-element analysis of geological materials on thin section. The sampling with an excimer laser with energy density of 8 J/cm^2 is appropriate for in-situ analysis of minerals on thin section based on ablation hole morphology. The rate of material removal is estimated from deep holes on a glass after 500 shots with energy on sample surface of 8 J/cm^2 to be approximately 0.2ƒﾊm/pulse. 150-200 shots might be available for a sample prepared as normal thin section (30ƒﾊm in thickness). All data were obtained by ablating in He gas prior to combination with the dominant Ar carrier flow because ablation in He minimized post-ablation surface condensation, resulting in high sensitivity. We examined the relationship between the size of laser-ablation hole and sensitivity of analysis in conducting in-situ simultaneous quantitative LA-ICP-MS analysis of 37 elements including rare earth elements (REEs). The diameter of laser beam can be as small as 30ƒﾊm to obtain sufficiently good dataset for trace-element concentrations of minerals from thin section

A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach

AbstractWe isolated a cDNA clone encoding a water channel protein, aquaporin (AQP), from human stomach. The encoded protein consisted of 323 amino acid residues, containing six putative transmembrane domains. The protein was designated human aquaporin 4 (hAQP4) because of its 94% sequence similarity to rat brain AQP4. Expression of hAQP4 cRNA in Xenopus oocytes resulted in a significant increase in osmotic water permeability, indicating that this protein functions as a water channel. Northern blot analysis demonstrated a strong signal of hAQP4 mRNA in brain, lung, and skeletal muscle as well as in stomach. Immunohistochemical experiments with human stomach tissues showed that hAQP4 as a protein is expressed mainly in cells located in the glandular portion of the fundic mucosa. These include chief cells which secrete pepsinogen and parietal cells which secrete hydrochloric acid. These results strongly indicate that hAQP4 is a principal factor involved in the osmotic regulation of pepsinogen and acid secretion in the stomach

T-cell counts in peripheral blood at leukapheresis predict responses to subsequent CAR-T cell therapy

CAR-T細胞の「原料の質」が治療効果と相関 --細胞採取時のリンパ球数がCAR-T細胞の体内での増殖と治療効果を予測する--. 京都大学プレスリリース. 2022-11-22.Prediction of responses to chimeric antigen receptor (CAR)-T cell therapies is essential to maximize their therapeutic efficacy for diffuse large B-cell lymphoma (DLBCL). While several tumor-intrinsic risk factors of resistance and/or early relapse have been identified, clinically useful markers that determine potential activity of CAR-T cells have not been fully investigated. T-cell property at the time of leukapheresis may serve as such a marker. Therefore, we evaluated the clinical impact of CD3⁺ cell count in peripheral blood at leukapheresis on clinical outcomes of CAR-T cell therapy. In total, 44 patients with relapsed or refractory (r/r) DLBCL who received tisagenlecleucel at Kyoto University Hospital were included. According to CD3⁺ cell counts, patients were categorized into CD3[LOW] and CD3[HIGH] groups with a threshold of 553/μL, based on receiver operating characteristic curve analysis. 1-year progression-free survival was significantly higher in the CD3[HIGH] group than the CD3[LOW] group (68.3% vs. 17.3%; adjusted hazard ratio [aHR], 0.37; p = 0.042). Overall survival was also superior in the CD3[HIGH] group (aHR, 0.24; p = 0.043). Moreover, higher CD3⁺ cell counts at leukapheresis were associated with significantly higher lymphocyte counts in peripheral blood at day 7 after CAR-T cell infusion (median 860 vs. 420/μL, P = 0.021), suggesting more extensive expansion of infused CAR-T cells in vivo. In conclusion, we demonstrated that the CD3⁺ cell count at leukapheresis predicts both expansion of CAR-T cells after infusion and outcomes of CAR-T cell therapy, and are useful for building comprehensive therapeutic strategies at the time of leukapheresis

The solution introduction ICP-MS technique to trace element analysis of rocks

Department of Earth Sciences, Faculty of Science, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa UniversityThe solution introduction ICP-MS technique for trace element analysis of rock samples was constructed at Kanazawa University. Trace element concentrations of geological standards (JB-2, JP-1, JA-1, and JGB-2) and Avacha peridotite xenoliths, Russia, which are strongly depleted in major elements and the hardest matter for analysis, were determined by the ICP-MS equipment. The values of concentration of middle to heavy masses (Rb-U) in geological standards coincide with those reported by other studies with ICP-MS techniques. The reproducibility is within 5% of differences of values of Rb to Hf in JB-2 in response to the changes in dates, dilutions and calibration methods. In the case of peridotites (low trace elements concentrations in the order of ppb to sub-ppb), relative standard deviations and relative differences among the runs under the various conditions are larger than in basalt with trace element concentrations in the order of ppm. Especially, large relative standard deviations (>10s%) for alkaline elements (Li, Rb, Cs), HFSE (Zr, Nb, Ta), Pb and Bi are shown in the refractory Avacha peridotite xenoliths with trace element concentrations in the order of sub-ppb. The solution introduction ICP-MS technique is a powerful tool for a precise insight into trace element characteristics of rocks of wide chemical compositions

Development of a quantitative prediction model for peripheral blood stem cell collection yield in the plerixafor era

BACKGROUND AIMS: Predicting autologous peripheral blood stem cell (PBSC) collection yield before leukapheresis is important for optimizing PBSC mobilization and autologous stem cell transplantation (ASCT) for treating hematological malignancies. Although guidelines for plerixafor usage based on peripheral blood CD34+ (PB-CD34+) cell count are available, their predictive performance in the real world remains unclear. METHODS: This study retrospectively analyzed 55 mobilization procedures for patients with non-Hodgkin lymphoma or multiple myeloma and developed a novel quantitative prediction model for CD34+ cell collection yield that incorporated four clinical parameters available the day before leukapheresis; namely, PB-CD34+ cell count the day before apheresis (day -1 PB-CD34+), number of prior chemotherapy regimens, disease status at apheresis and mobilization protocol. RESULTS: The effects of PB-CD34+ cell counts on CD34+ cell collection yield varied widely per patient characteristics, and plerixafor usage was recommended in patients with poorly controlled disease or those with a history of heavy pre-treatments even with abundant day -1 PB-CD34+ cell count. This model suggested a more proactive use of plerixafor than that recommended by the guidelines for patients with poor pre-collection condition or those with a higher target number of CD34+ cells. Further, the authors analyzed the clinical outcomes of ASCT and found that plerixafor use for stem cell mobilization did not affect short- or long-term outcomes after ASCT. CONCLUSIONS: Although external validations are necessary, the results can be beneficial for establishing more effective and safer mobilization strategies

The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study

Showing the effects of OP3-4 on the proliferation and differentiation of cartilage cell line ATDC5. A Results of proliferation assay on day 1 with the noninduction medium. B Alcian blue-positive area ratio in the cartilage induction medium on day 10. **p <0.01 vs. vehicle control, #p <0.05 vs. 100 ÎźM OP3-4. (JPEG 384 kb

Validation of the Burden Index of Caregivers (BIC), a multidimensional short care burden scale from Japan

BACKGROUND: We constructed a concise multidimensional care burden scale that reflects circumstances unique to Japan, with a focus on intractable neurological diseases. We surveyed 646 family caregivers of patients with intractable neurological diseases or stroke using 28 preliminary care burden scale items obtained from qualitative research. The results were used to finalize the feeling of care burden scale (BIC: burden index of caregivers), and verify its reliability and validity. METHODS: The survey was conducted among caregivers providing home health care to patients with intractable neurological diseases (PD [Parkinson's disease], SCD [spinocerebellar degeneration], MSA [multiple system atrophy], and ALS [amyotrophic lateral sclerosis]) or CVA (cerebrovascular accident) using a mailed, self-administered questionnaire between November, 2003 and May, 2004. RESULTS: Response rates for neurological and CVA caregivers were 50% and 67%, respectively, or 646 in total (PD, 279; SCD, 78; MSA, 39; ALS, 30; and CVA, 220). Item and exploratory factor analyses led to a reduction to 11 items, comprising 10 items from the 5 domains of time-dependent burden, emotional burden, existential burden, physical burden, and service-related burden; and 1 item on total burden. Examination of validity showed a moderate correlation between each domain of the BIC and the SF-8 (Health related quality of life scale, Short Form-8), while the correlation coefficient of the overall BIC and CES-D was 0.62. Correlation between the BIC and ZBI, a preexisting care burden scale, was high (r = 0.84), while that with the time spent on providing care was 0.47. The ICC (Intraclass correlation coefficient) by test-retest reliability was 0.83, and 0.68 to 0.80 by individual domain. CONCLUSION: These results show that the BIC, a new care burden scale comprising 11 items, is highly reliable and valid

The Effects of Natural Variability and Climate Change on the Record Low Sunshine over Japan during August 2017

EXPLAINING EXTREME EVENTS OF 2017 FROM A CLIMATE PERSPECTIVE (Supecial Supplement to the Bulletin of the American Meteorological Society, Vol.100, No.1, January 2019

On-line microdevice for stress proteomics

The handing of the cells or tissues is essential for proteomics research or drug screening, where labor is not avoidable. The steps of cell wash, protein extraction, protein denaturing are complicated procedures in conventional method using centrifugation and pipetting in the laboratory. This is the bottle-neck for proteome research. To solve these problems, we propose to utilize the nanotechnology, which will improve the proteomics methodology. Utilizing the nanotechnology, we developed a novel microseparation system, where centrifugation and pipetting are needless. This system has a nanostructured microdevice, by which the cell handling, protein extraction, and antibody assay can be performed. Since cell transfer is needless, all cells are corrected without any loss during the cell-pretreatment procedures, which allowed high reproducibility and enabled the detection of low amount of protein expression. Utilizing the microdevice, we analyzed the stress induced proteins. We further succeeded the screening of food that was useful for immunity and found that an extraction from seaweed promoted the apoptosis of T-lymphoblastic cells. Here, we present an on-line microdevice for stress proteomics