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CD109 on dendritic cells regulates airway hyperreactivity and eosinophilic airway inflammation
Get PDF浜松医科大学博士（医学）dotoral医学系研究科Asthma is a chronic airway inflammatory disease characterized by airway hyperreactivity (AHR) and eosinophilic airway inflammation. Dendritic cells (DCs) are essential for the development of asthma via presenting allergens, causing Th2 skewing and eosinophil inflammation. Recent studies have revealed that CD109, a glycosylphosphatidylinositolanchored glycoprotein, is involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis and psoriasis. However, no study has addressed the role of CD109 in asthma. This study sought to address the role of CD109 on DCs in the development of AHR and allergic inflammation. CD109 deficient mice (CD109−/− mice) were sensitized with house dust mite (HDM) or ovalbumin and compared to wild-type (WT) mice for induction of AHR and allergic inflammation. CD109-deficient mice had reduced AHR and eosinophilic inflammation together with lower Th2 cytokine expression compared to WT mice. Interestingly, CD109 expression was induced in lung conventional DC2s (cDC2s), but not lung cDC1s, upon allergic challenge. Lung cDC2s from CD109−/− mice had a poor ability to induce cytokine production in ex vivo DC-T cell cocultures with high expression of RUNX3, resulting in suppression of Th2 differentiation. Adoptive transfer of bone-marrow-derived CD109−/− DCs loaded with HDM failed to develop AHR and eosinophilic inflammation. Finally, administration of monoclonal anti-CD109 antibody reduced airway eosinophils and significantly decreased AHR. Our results suggest the involvement of CD109 in asthma pathogenesis. CD109 is a novel therapeutic target for asthma.doctoral thesi
UBL3 interacts with alpha-synuclein in cells and the interaction is downregulated by the EGFR pathway inhibitor osimertinib
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as α-synucleinopathies. Alpha-synuclein (α-syn) has been widely studied for its involvement in α-synucleinopathies. However, it is still unknown whether UBL3 interacts with α-syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and α-syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with α-syn by the Gaussia princeps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with α-syn in cells and is significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for α-synucleinopathies in the future.doctoral thesi
Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Preoperative four-dimensional flow-sensitive magnetic resonance imaging assessment of aortic side branches as a method to predict risk for type II endoleak resulting in sac enlargement after EVAR
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Stereoselective interaction of tolvaptan with amiodarone under racemic metabolic impact by CYP3A5 genotypes in heart failure patients
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients
Get PDFPurpose: Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia status and clinical responses in head and neck cancer patients.
Methods: Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Plasma concentrations of total and free aprepitant and ND-AP were determined at 24 hours after a 3-day aprepitant treatment. The clinical responses to aprepitant and degrees of cachexia status were assessed using a questionnaire and Glasgow Prognostic Score (GPS).
Results: Serum albumin level was negatively correlated with the plasma concentrations of total and free aprepitant but not ND-AP. The serum albumin level had a negative correlation with the metabolic ratio of aprepitant. The patients with GPS 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant.
Conclusion: Cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant
Umbilical granuloma: current understanding of its pathophysiology, clinical presentation, and management
Get PDF臍肉芽腫は，臍部にみられる肉芽組織からなる赤色結節で，臍帯脱落後の上皮形成過程の遅れによって臍帯断端が残存し肉芽として増殖したものである．
発生頻度は，臍帯の処理や衛生状況によって様々であり1～13%と報告されている．原因としては，感染・炎症説のほか異物説，臍動静脈血流遺残説がある．ほとんどは臍分泌物と肉芽組織の肉眼的所見により容易に診断できるが，時に外科的介入が必要な臍ポリープ，臍腸瘻，尿膜管遺残との鑑別を要する．
治療は，硝酸銀焼灼が一般的に行われているが，ステロイド外用療法の有用性も示されており，海外では食塩散布や硫酸銅焼灼，抗菌薬局所投与も行われている．難治性の臍肉芽腫では，液体窒素凍結や電気焼灼，外科的切除も考慮される．臍肉芽腫の予防に，臍帯結紮（クランプ）時には低位クランプ，臍帯断端のケアでは局所の消毒よりも dry code care が有用な可能性があり，臍帯の乾燥・収斂を目的とする粉末の散布は現在では推奨されていない.journal articl