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間欺的低酸素被曝は、脂肪細胞においてmicro RNA-452の発現低下を介してCCL2、Resistin、TNFαの発現上昇を引き起こす
Sleep apnea syndrome (SAS), characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), is a risk factor for insulin resistance. Recently, IH is considered to independently cause adipose tissue inflammation/dysfunction, leading to worsening insulin resistance; however, the detailed mechanism remains unknown. We exposed mouse 3T3-L1 and human SW872 adipocytes to experimental IH or normoxia for 24 h, and analyzed mRNA expression of several adipokines. We found that the mRNA levels of RETN, TNFα, and CCL2 in SW872 and 3T3-L1 adipocytes were significantly increased by IH, whereas the promoter activities of these genes were not increased. A target mRNA search of microRNA (miR)s revealed that all human mRNAs have a potential target sequence for miR-452. The miR-452 level of IH-treated cells was significantly decreased compared to normoxia-treated cells. MiR-452 mimic and non-specific control RNA (miR-452 mimic NC) were introduced into SW872 cells, and the IH-induced up-regulation of the genes was abolished by introduction of the miR-452 mimic but not by the miR-452 mimic NC. These results indicate that IH stress down-regulates the miR-452 in adipocytes, resulting in increased levels of RETN, TNFα, and CCL2 mRNAs, leading to insulin resistance in SAS patients.博士(医学)・甲第729号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/)
ミスマッチ修復遺伝子発現欠損を伴う子宮体癌のMRI所見と臨床像
Purpose: The purpose of this study was to identify the magnetic resonance imaging (MRI) features of uterine endometrial carcinoma (EC) with DNA mismatch repair (MMR) deficiency. Materials and methods: This was a retrospective study approved by our institutional review board. The study included 118 patients pathologically diagnosed as having EC in our institution from April 2014 to December 2016. Of 118 patients, 8 were excluded because of insufficient data. Immunohistochemical analysis of MMR was performed retrospectively to observe the expressions of MLH1, MSH2, MSH6, and PMS2. A tumor with MMR deficiency was detected in 17 of 110 cases (15%). Clinical background characteristics and MRI findings were reviewed. These findings were compared between MMR deficiency group and the other group as a control group. Statistical significance was determined using the Fisher's exact test and the Mann-Whitney U test, as appropriate. Results: The clinical background characteristics of patients with EC with MMR deficiency were not significantly different from those of other patients. On MRI, the tumor was significantly more often located in the lower uterine site (MMR(-) vs. MMR(+): 29.4 vs. 8.9% [p = 0.0366]). Conclusion: EC with MMR deficiency tends to be located lower in the uterus, though most other findings were not significantly different from those of EC without MMR deficiency.博士(医学)・甲第749号・令和2年6月30日© Japan Radiological Society 2018© 2018 Springer Nature Switzerland AG. Part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in Japanese journal of radiology. The final authenticated version is available online at: http://doi.org/10.1007/s11604-018-0741-4
線形二次曲線モデルの寡分割照射への適用性
Background: The linear-quadratic (LQ) model is used for evaluating fractionation schedules in radiation oncology. It has been suggested that the biologically effective dose based on the LQ model cannot be applied to hypofractionated radiotherapy. Methods: Glioblastoma cells were transplanted into nude mice. Four equivalent dose fractionation schedules (12 Gy/1 fraction (fr). 15.06 Gy/2 fr, 18.16 Gy/4 fr, and 20.96 Gy/8 fr) were calculated based on the LQ model. The tumor size was measured to evaluate the number of days required for the relative tumor volume to double and become five t imes the initial value (TGD₂ and TGD₅, respectively). A histopathological study was performed after the evaluation of growth delay. Result: The mean TGD₂ of the unirradiated control group and 12 Gy/1 fr, 15.06 Gy/2 fr. 18.16/4 fr, and 20.96 Gy/8 fr groups was 5.69, 22.64, 37.26. 36.81, and 28.96 days, respectively. The mean TGD₅ was 17.83, 48.03. 60.30, 60.40, and 64.94 days, respectively. All TGDs of the irradiated groups were longer than those of the control group. However, no significant differences were observed among the four irradiated groups. Histologically, irregular giant cells were found, but there were no significant differences among the four groups. There was no significant difference in the Ki-67 labeling index and the CD133 and CD44 expression among the groups. Conclusion: The four dose fractionation schedules equivalent to 12 Gy/1 fr yielded comparable responses, suggesting that the LQ model may be applicable to hypofractionated radiotherapy, with a high dose per fraction of up to 12 Gy.博士(医学)・甲第756号・令和2年9月30
難聴患者における耳鳴り治療のための補聴器の副次的効果の遡及的評価
Objective: Acoustic therapies including hearing aids and tinnitus control instruments are widely used in Japan but without high levels of evidence. The outpatient hearing aid clinic at our institution fits patients with hearing aids and instructs patients on how to use them to control tinnitus if present. In this study, we examined the effects of this approach on tinnitus. Methods: One hundred and eleven of 138 patients who visited our hearing aid clinic from April 2016 to September 2018 purchased hearing aids after fitting. Sixty-six of these patients (31 men, 35 women; mean age 78.0 ± 8.0 years) had both hearing loss and tinnitus and were enrolled. The tinnitus was bilateral in 41 patients and unilateral in 25 (poor hearing ear, n = 16, good hearing ear, n = 9). Hearing aids were worn bilaterally by 23 patients and unilaterally by 43 (89 devices). Seventeen of the 23 patients wearing bilateral hearing aids had bilateral tinnitus and 6 had unilateral tinnitus, i.e., in 40 ears, the tinnitus side matched the hearing aid side (40 devices) and in 6 ears did not (6 devices). Twenty-four of 43 patients wearing unilateral hearing aids had bilateral tinnitus, meaning that in 24 ears the tinnitus side matched the hearing aid side (24 devices). In six of the remaining 19 cases with unilateral tinnitus, the hearing aid and tinnitus were on the same side (6 devices) and in 13 were on opposite sides (13 devices). Changes in the Tinnitus Handicap Inventory (THI), visual analog scale (VAS, for tinnitus discomfort, severity, and persistence), and Hospital Anxiety and Depression Scale scores were measured immediately before using a hearing aid and 12 months later. Results: Significant effects of hearing aids on tinnitus were observed in all subjects (THI, p = 0.0000030), VAS (severity, p = 0.000000066; discomfort, p = 0.0000013). Significant effects were observed with bilateral hearing aids (THI, p = 0.0012; VAS for severity, p = 0.00069; VAS for discomfort, p = 0.00052) and with unilateral hearing aids (THI, p = 0.00055; VAS for severity, p = 0.000034; VAS for discomfort, p = 0.00007). Spearman's rank correlation coefficient showed a significant positive correlation between the THI and VAS scores (p = 0.0033). In cases of bilateral tinnitus, significant differences were observed with bilateral hearing aids (THI, p = 0.011; VAS for severity, p = 0.0019; VAS for discomfort; p = 0.020) and with unilateral hearing aids (THI, p = 0.00069; VAS for severity, p = 0.00071; VAS for discomfort, p = 0.000093). Conclusion: Acoustic therapy using hearing aids was effective for tinnitus. Even when bilateral, a unilateral hearing aid is able to improve tinnitus. When unilateral, the ipsilateral hearing aid is able to improve tinnitus.博士(医学)・甲第755号・令和2年9月30日© 2020 Oto-Rhino-Laryngological Society of Japan Inc. Published by Elsevier B.V. All rights reserved
下顎再建後の三次元画像計測による顔面対称性の評価:主観的評価との比較
Introduction: The assessment of facial symmetry, after mandibular reconstruction, currently relies on subjective esthetic assessment by an evaluator. The present study aimed to compare conventional subjective assessment with quantitative evaluation by three-dimensional (3D) stereophotogrammetry of facial cosmetic symmetry. Methods: This retrospective study enrolled 20 patients who underwent mandibular reconstruction with free fibula flap after segmental resection between 2014 and 2018. Subjective assessments were performed by seven clinicians at 6-12 months after surgery. Simultaneously, lower face symmetry was measured by 3D stereophotogrammetry with the VECTRA H1 system and recorded as the root mean square deviation (RMSD). Data from the subjective and quantitative evaluations were compared using Spearman's rank correlation coefficient. Results: The results showed that subjective assessments were strongly and negatively correlated with RMSD (P=0.00000128). This confirmed that RMSD, obtained by 3D stereophotogrammetry, reflected the subjective assessment of symmetry in our cohort. Conclusions: Three-dimensional stereophotogrammetry of facial cosmetic symmetry will be an available quantitative method for patients with head and neck cancer after mandibular reconstruction.博士(医学)・乙第1475号・令和2年9月30日© 2020 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
For the purpose of situation judgment capacity building in fundamental nursing practice and challenges of class development.
高ずり応力下において、エミシズマブは血友病A 患者の全血の血栓形成を増加させる
Background: Emicizumab is a bispecific antibody to factor (F) IXa and FX that mimics the FVIIIa cofactor function. Emicizumab prophylaxis markedly decreases bleeding episodes in patients with hemophilia A (PwHAs), irrespective of the presence of FVIII inhibitors. However, thrombotic microangiopathy (TMA) was reported when repeated high doses of activated prothrombin complex concentrates (aPCC) were concomitantly used with emicizumab. Although bypassing agents (BPAs) are vital in the hemostatic treatment for PwHAs with inhibitors, the mechanism of emicizumab-related TMA remains unclear. Aim: To assess the risk of excessive thrombus formation associated with BPAs and emicizumab under high shear conditions. Methods: Perfusion flow-chamber experiments under high shear conditions were performed using whole blood from PwHAs in the presence of emicizumab without or together with FVIII or BPAs ex vivo. Results: Emicizumab (100 μg/mL) added ex vivo to whole blood from PwHAs improved defective thrombus formation in a similar manner to that observed with the addition of recombinant FVIII at the early phase, while FVIII continued to be important at the later stages. aPCC (1.2 U/mL equivalent to 100 U/kg) or recombinant FVIIa (1.1 µg/mL; equivalent to 90 µg/kg) together with emicizumab further promoted platelet interactions and fibrin formation ex vivo but did not induce excessive thrombus formation. Conclusion: Emicizumab enhanced thrombin generation at local sites and improved defective hemostasis in whole blood from PwHAs under high shear conditions. Simple concomitant use of BPAs with emicizumab did not mediate excessive thrombus formation and remains an option for hemostatic management of emicizumab-treated PwHAs with inhibitors.博士(医学)・乙第1487号・令和2年12月24日© 2020. Thieme. All rights reserved.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1055/s-0040-1716542