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非乳頭部十二指腸癌における至適リンパ節郭清範囲とリンパ節転移個数に基づく領域リンパ節転移分類の妥当性の検討
Get PDF新潟大学Niigata University博士（医学）新大院博（医）第1170
男性における経カテーテル的大動脈弁留置術の全死亡予測因子について : LAPLACETAVIレジストリーより
Get PDF新潟大学Niigata University博士（医学）Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36–3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13–2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06–1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36–2.98),1.37 (95% CI: 0.75–2.48), and 1.13 (95% CI: 0.75–2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were indepen-dently associated with all-cause mortality following TAVR in men.IJC Heart & Vasculature
IJC Heart & Vasculature
International journal of cardiology. Heart & vasculature. 2023, 48, 101257新大院博（医）第1179
ポリメリルメタクリレート膜を用いた後希釈オンライン血液透析濾過によるα1-ミクログロブリンの除去 : 非盲検単群試験
Get PDF新潟大学Niigata University博士（医学）Introduction: The removal of low- and medium-molecular-weight proteins has been improved with online hemo-diafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treat-ment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and β2-micro-globulin (β2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in compar-ison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. Methods: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, β2-m, small mole-cules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. Results: Clearance rates of α1-m at 60 min were −2.8 ± 5.2 mL/min with Pre-PS, −0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. Conclusion: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effec-tively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.Shiori Yoshida, Suguru Yamamoto, Daisuke Miyauchi, Ryohei Terashima, Atsushi Hashimoto, Haruna Miyazawa, Takahiro Tanaka, Masahiro Ishizawa, Mototsugu Tanaka, Yoshihiko Tomita, Ikuo Aoike, Shin Goto, Ichiei Narita; Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study. Blood Purif 1 February 2024; 53 (2): 123–129. https://doi.org/10.1159/000534459新大博（医）第1199
マウス臼歯の根尖側セメント質の最表層には無細胞外部線維性セメント質が常に存在する
Get PDF新潟大学Niigata University博士（歯学）The cementum is a highly mineralized tissue that covers the tooth root. The regional differences among the types of cementum, especially in the extrinsic fibers that contribute to tooth support, remain controversial. Therefore, this study used second-harmonic generation imaging in conjunction with automated collagen extraction and image analysis algorithms to facilitate the quantitative examination of the fiber characteristics and the changes occurring in these fibers over time. Acellular extrinsic fiber cementum (AEFC) was invariably observed in the superficial layer of the apical cementum in mouse molars, indicating that this region of the cementum plays a crucial role in supporting the tooth. The apical AEFC exhibited continuity and fiber characteristics comparable with the cervical AEFC, suggesting a common cellular origin for their formation. The cellular intrinsic fiber cementum present in the inner layer of the apical cementum showed consistent growth in the apical direction without layering. This study highlights the dynamic nature of the cementum in mouse molars and underscores the requirement for re-examining its structure and roles. The findings of the present study elucidate the morphophysiological features of cementum and have broader implications for the maintenance of periodontal tissue health.Iwama H, Kaku M, Thant L, et al. Acellular Extrinsic Fiber Cementum Is Invariably Present in the Superficial Layer of Apical Cementum in Mouse Molar. Journal of Histochemistry & Cytochemistry. 2024;72(2):109-120. doi:10.1369/00221554241229130This is the submitted version of the article, accepted for publication in the Journal of Histochemistry & Cytochemistry.新大院博(歯)第558
Fibulin-4は肝硬変患者における細胞外小胞由来の線維化マーカーとなり得るステナブルなダイヤモンド電極を用いた,安価な血漿中薬物濃度測定法の創出
No full text新潟大学Niigata University博士（医学）Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor progno-sis, highlighting the importance of non-invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin-4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child–Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child–Pugh class B–C (39 without HCC, 26 with HCC)], fibulin-4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin-4/CD9 ratio was significantly higher in patients with varices. Immu-nostaining also revealed strong fibulin-4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin-4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis.Kumagai, M., Tsuchiya, A., Yang, Y., Takeda, N., Natsui, K., Natusi, Y., Tomiyoshi, K., Yamazaki, F., Koseki, Y., Shinchi, H., Imawaka, N., Ukekawa, R., Nishibu, T., Abe, H., Sasaki, T., Ueda, K. and Terai, S. (2024), Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis. FEBS Open Bio, 14: 1264-1276. https://doi.org/10.1002/2211-5463.13842新大院博（医）第1206
GPATCH4は核小体の形態に寄与しその機能障害は細胞生存に関与する
Get PDF新潟大学Niigata University博士（医学）The nucleolus serves a multifaceted role encompassing not only rRNA transcription and ribosome synthesis, but also the intricate orchestration of cell cycle regulation and the modulation of cellular senescence. G-patch domain containing 4 (GPATCH4) stands as one among the nucleolar proteins; however, its functional significances remain still unclear. In order to elucidate the functions of GPATCH4, we examined the effects of its dysfunction on cellular proliferation, alterations in nucleolar architecture, apoptotic events, and cellular senescence. Through experimentation conducted on cultured neuroblastoma SH-SY5Y cells, the reduction of GPATCH4 caused inhibition of cellular proliferation, concurrently fostering escalated apoptotic susceptibilities upon exposure to high-dose etoposide. In the realm of nucleolar morphology comparisons, a discernible decline was noted in the count of nucleoli per nucleus, concomitant with a significant expansion in the area occupied by individual nucleoli. Upon induction of senescence prompted by low-dose etoposide, GPATCH4 knockdown resulted in decreased cell viability and increased expression of senescence-associated markers, namely senescence-associated β-galactosidase (SA-β-GAL) and p16. Furthermore, GPATCH4 dysfunction elicited alterations in the gene expression profile of the ribosomal system. In sum, our findings showed that GPATCH4 is a pivotal nucleolar protein that regulates nucleolar morphology and is correlated with cell viability.Kazuki Kodera, Ryuichi Hishida, Akiko Sakai, Hiromi Nyuzuki, Noriko Matsui, Tomoyuki Yamanaka, Akihiko Saitoh, Hideaki Matsui,
GPATCH4 contributes to nucleolus morphology and its dysfunction impairs cell viability,
Biochemical and Biophysical Research Communications,
Volume 693,
2024,
149384,
ISSN 0006-291X,
https://doi.org/10.1016/j.bbrc.2023.149384.
(https://www.sciencedirect.com/science/article/pii/S0006291X2301478X)新大院博（医）第1218
黄斑円孔と健常僚眼における無血管領域の面積比と長期視機能との関連
Get PDF新潟大学Niigata University博士（医学）Purpose This study is to investigate the relationship between long-term changes in the foveal avascular zone (FAZ) and visual function of eyes with macular hole (MH) and compare the relationship between the FAZ of MH eyes and fellow eyes. Methods This study included 31 patients with unilateral MH who underwent vitrectomy and their fellow eyes. Best-corrected visual acuity (BCVA) and metamorphopsia were measured preoperatively and at 1, 3, 6, and 12 months postoperatively. We evaluated retinal parameters using optical coherence tomography (OCT) and the superficial FAZ using OCT angiography. The FAZ ratio was defined as follows: (preoperative FAZ area of the MH eye)/(FAZ area of the fellow eye). Results The preoperative FAZ area of MH eyes was 0.42±0.08 mm2, which decreased to 0.24±0.07 mm2 1 month post-operatively(p＜0.001) and slightly increased to 0.25±0.06 mm2 12 months postoperatively(p＝1.000). The FAZ area did not differ significantly from that of fellow eyes (0.39±0.06 mm2, p=0.281). The FAZ area of MH eyes was not associated with visual function at any time point. The FAZ ratio showed a correlation with the preoperative, 6-month, and 12-month BCVA (r=0.604,p<0.001; r=0.510,p=0.003; and r=0.475,p=0.007, respectively). Conclusions A larger FAZ in the MH eye than that in the fellow eye is associated with poorer long-term visual acuity. The preoperative comparison of the FAZ of the MH eye with that of the fellow eye may be a biomarker for predicting long-term visual acuity.Ando, T., Terashima, H., Yoshida, H. et al. Relationship between long-term visual function and the ratio of foveal avascular zone area in eyes with macular hole and healthy fellow eyes. Graefes Arch Clin Exp Ophthalmol 262, 2403–2410 (2024). https://doi.org/10.1007/s00417-024-06433-wThis version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00417-024-06433-w新大院博（医）第1220