Nara Medical University Hospital
Global Institutional repository of Nara Medical UniversityNot a member yet
3071 research outputs found
Sort by
C9orf72リピート異常伸長より生じる毒性ペプチドは相分離制御因子の機能を阻害する
Get PDFNuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration.博士（医学）・甲第826号・令和4年3月15日© The Author(s) 2021. Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/
超音波加温による動脈塞栓後の肝腫瘍内部のリピオドール集積検出能に関する生体内での検討
Get PDFComputed tomography (CT) is the standard method to evaluate Lipiodol deposition after transarterial embolization (TAE) for a long period. However, iodine but not Lipiodol can be observed on CT. A minimally invasive other method to detect Lipiodol has been needed to evaluate accurate evaluation after procedure. The purpose of this study was to evaluate the efficacy of using the rate of change in sound velocity caused by ultrasonic heating to reflect Lipiodol accumulation after TAE in a rat liver tumor model. We analyzed the association of this developed technique with CT images and histological findings. Eight rats bearing N1S1 cells were prepared. After confirmation of tumor development in a rat liver, Lipiodol was injected via the hepatic artery. Seven days after TAE, CT scan and sound velocity changes caused by ultrasonic heating were measured, and then the rats were sacrificed. An ultrasonic pulse-echo method was used to measure the sound velocity. The temperature coefficient of the sound velocity in each treated tumor was evaluated and compared with the mean CT value and the histological Lipiodol accumulation ratio. Pearson's correlation coefficients were calculated to assess the correlation between the measured values. The correlation coefficient (r) of the mean CT value and histological Lipiodol accumulation ratio was 0.835 (p = 0.010), which was considered statistically significant. Also, those of the temperature coefficient of the sound velocity and the histological Lipiodol accumulation ratio were statistically significant (r = 0.804; p = 0.016). To our knowledge, this is the first study that reported the efficacy of ultrasonic heating to detect Lipiodol accumulation in rat liver tumors after TAE. Our results suggest that the rate of change in sound velocity caused by ultrasonic heating can be used to evaluate Lipiodol accumulation in liver tumors after TAE, and thus could represent an alternative to CT in this application. This new innovative technique is easy to treat and less invasive in terms of avoiding radiation compared with CT.博士（医学）・甲第836号・令和4年3月15日© 2021 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 (https://creativecommons.org/licenses/by/4.0/)
早期関節リウマチ患者において関節エコーで検出される前足部滑膜炎は、手部滑膜炎とは異なり、28関節評価での疾患活動性スコアと正の相関を示さない
Get PDFObjective : This study aimed to clarify the relationship between the ultrasound (US)-detected forefoot synovitis and systemic disease activity and functional disability in patients with early rheumatoid arthritis (ERA). Methods : Thirty-eight ERA patients (6 men, 32 women) prior to initiation of tight-control treatment were included. Semiquantitative US assessment for bilateral finger, wrist, and forefoot joints was conducted using gray-scale (GS) and power Doppler (PD), and each summation was defined as hand, foot, and total scores. The accuracy of US based on the physical examination for the metatarsophalangeal (MTP) joints was determined. The relationshio between each US score and composite measures using 28-joint counts, serum biomarkers, and patient-reported functional impairment scores was analyzed. Results : Based on MTP joint swelling and tenderness, for GS and PD scores ≥ 1, the positive predictive value was low (GS: 16.0%, 12.5%; PD: 38.5%, 17.5%). Hand US scores, especially in hand PD scores, showed a significant moderate positive correlation with disease activity scores and biomarkers; however, foot US scores showed no positive correlation with any factor. The results were robust in multivariate analyses that incorporated each score and were adjusted for age. Conclusions : US-detected forefoot synovitis may not be reflected in the composite disease activity scores not including direct forefoot assessment in ERA patients.博士（医学）・乙第1521号・令和4年3月15
地域の一般耳鼻咽喉科医よって外来経過観察された原因不明のめまい患者の内訳
Get PDFObjectives: The purpose of this study was to access the contribution of vertigo/dizziness-related patients' interview and examinations during short-term hospitalization in determining the accurate final diagnosis of vertigo/dizziness of unknown origin. Methods: We reviewed 1905 successive vertigo/dizziness patients at the Vertigo/Dizziness Center of Nara Medical University, who were introduced from general otolaryngologists at outpatient town clinic from May 2014 to April 2020. However, 244 patients were diagnosed with vertigo/dizziness of unknown origin (244/1905; 12.8%). Of these patients, 240 were hospitalized and underwent various examinations, including caloric test (C-test), video head impulse test (vHIT), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV), inner ear magnetic resonance imaging (ieMRI), Schellong test (S-test), and self-rating questionnaires of depression score (SDS). Results: According to the examination data, together with interviewed vertigo/dizziness characteristics and daily changeable nystagmus findings, the final diagnoses were as follows: benign paroxysmal positional vertigo (BPPV: 107/240; 44.6%), orthostatic dysregulation (OD: 56/240; 23.3%), vestibular peripheral disease (VPD: 25/240; 10.4%), vestibular migraine (VM: 14/240; 5.8%), Meniere's disease (MD: 12/240; 5.0%), gravity perception disturbance (GPD: 10/240; 4.2%), psychogenic vertigo (Psycho: 10/240; 4.2%), and unknown (Unknown: 6/240; 2.5%). Supporting factors of final diagnosis was seen in gender, evoked dizziness, and positional nystagmus as BPPV; in evoked dizziness, S-test, and hypertension as OD; in evoked dizziness, head shaking after nystagmus, C-test, and vHIT as VPD; in gender, headache, and S-test as VM; in ear fullness and ieMRI as MD; in gender, evoked dizziness, and SVV as GPD; and in SDS as Psycho. To sum up, the ratios of Unknown were significantly reduced by this short-term hospitalization (244/1905→6/240). Conclusions: The answer lists for vertigo/dizziness of unknown origin obtained in the present study may be helpful for future general otolaryngologists at outpatient town clinic to better attain an accurate final iagnosis.博士（医学）・乙第1523号・令和4年3月15日© 2020 Oto-Rhino-Laryngological Society of Japan Inc. Published by Elsevier B.V. All rights reserved
起立性めまいにおける起立時の椎骨動脈血流動態と血圧の影響
Get PDFObjectives: Orthostatic dizziness/vertigo (ODV) is a common symptom and is believed to occur due to the cerebral hypoperfusion caused by orthostatic hypotension (OH). However, the detailed mechanism underlying ODV onset is poorly understood. The vertebral artery (VA) mainly supplies blood to the central vestibular system; therefore, the orthostatic decrease of VA blood flow could possibly lead to ODV. This study investigated the orthostatic blood pressure and VA hemodynamics in ODV patients to elucidate the hemodynamic mechanism underlying ODV onset. Furthermore, the influence of orthostatic hypotension (OH) on VA hemodynamics was examined because OH is probably the most common cause of ODV. Methods: This study included 181 patients with ODV and 73 control patients without ODV. All subjects underwent an active standing test to measure the extracranial Doppler (ECD) sonography spectrum of the VA and blood pressure (BP). VA blood flow velocity and BP were simultaneously measured for each patient in the supine static position and then in the upright standing positions following 3 min of standing. We investigated the orthostatic change in the average of flow velocity in bilateral VAs (VAFV) and BP for ODV patients compared with the control patients. Result: VAFV in ODV patients was significantly reduced when standing up compared with the control patients. In the ODV patients, there was no difference in orthostatic decrease in VAFV between patients those with OH and without OH. However, the VAFV in the standing position was significantly lower in patients with OH than without OH. In cases with OH, the ODV patients exhibited a greater decrease in VAFV compared with the control patients, but this was not statistically significant. In the absence of OH, a significantly greater orthostatic decrease in VAFV was observed in ODV patients compared with the controls. Conclusion: Our findings suggest that the orthostatic decrease of VA blood flow is deeply involved in the hemodynamic mechanism underlying ODV onset and is possibly associated with OH and other etiologies.博士（医学）・乙第1524号・令和4年3月15日© 2021 Oto-Rhino-Laryngological Society of Japan Inc. Published by Elsevier B.V. All rights reserved
[Review] Mucous phenotype in prostate glands and prostate cancer
No full textMucus production in prostatic glands and prostate cancers is a relatively rare phenotype that is confirmed by goblet cell metaplasia and mucus staining. Mouse carcinogenesis models suggest that the mucin phenotype is in the noncanonical pathway and possesses a higher potential for malignancy.We found 16 mucin-positive cases in 98 human prostate cancers.There was no difference in Gleason score，vascular invasion，or perineural invasion among them. In contrast，the mucin-positive cases showed more pronounced tumor extension and higher nuclear atypia than the negative cases. In addition，pre-cancerous PIN lesions were observed in the mucin-negative cases but not in any of the positive cases. The goblet cell metaplasia in nonneoplastic prostatic glands is noteworthy as a possible precancerous status in a noncanonical carcinogenic pathway
急性心不全における退院時の尿素窒素分画排泄率の予後判定への有用性
Get PDFBackground Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group (P<0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P=0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m2, interaction P=0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.博士（医学）・甲第814号・令和4年3月15日Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made
