Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification

<p>Abstract</p> <p>Background</p> <p>Chondrogenesis and subsequent endochondral ossification are processes tightly regulated by the transcription factor Sox9 (SRY-related high mobility group-Box gene 9), but molecular mechanisms underlying this activity remain unclear. Here we report that coactivator-associated arginine methyltransferase 1 (CARM1) regulates chondrocyte proliferation via arginine methylation of Sox9.</p> <p>Results</p> <p>CARM1-null mice display delayed endochondral ossification and decreased chondrocyte proliferation. Conversely, cartilage development of CARM1 transgenic mice was accelerated. CARM1 specifically methylates Sox9 at its HMG domain <it>in vivo </it>and <it>in vitro</it>. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating <it>Cyclin D1 </it>expression and cell cycle progression of chondrocytes.</p> <p>Conclusion</p> <p>These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.</p

Cultivable Anaerobic Microbiota of Infected Root Canals

Objective. Periapical periodontitis is an infectious and inflammatory disease of the periapical tissues caused by oral bacteria invading the root canal. In the present study, profiling of the microbiota in infected root canals was performed using anaerobic culture and molecular biological techniques for bacterial identification. Methods. Informed consent was obtained from all subjects (age ranges, 34–71 years). Nine infected root canals with periapical lesions from 7 subjects were included. Samples from infected root canals were collected, followed by anaerobic culture on CDC blood agar plates. After 7 days, colony forming units (CFU) were counted and isolated bacteria were identified by 16S rRNA gene sequencing. Results. The mean bacterial count (CFU) in root canals was (0.5 ± 1.1) × 106 (range 8.0 × 101–3.1 × 106), and anaerobic bacteria were predominant (89.8%). The predominant isolates were Olsenella (25.4%), Mogibacterium (17.7%), Pseudoramibacter (17.7%), Propionibacterium (11.9%) and Parvimonas (5.9%). Conclusion. The combination of anaerobic culture and molecular biological techniques makes it possible to analyze rapidly the microbiota in infected root canals. The overwhelming majority of the isolates from infected root canals were found to be anaerobic bacteria, suggesting that the environment in root canals is anaerobic and therefore support the growth of anaerobes

頸動脈狭窄に対する自己拡張型ステント留置後フォローアップ時のステント径と内腔の検討

Purpose: We examined postoperative stent and lumen expansions after carotid artery stenting (CAS) in patients with carotid artery stenosis. Furthermore, we investigated factors influencing the stent and lumen expansions in a follow-up period. Subjects: 134 cases (128 patients) who underwent CAS and performed follow-up cerebral angiography 12 months after CAS were enrolled into this study. The stenosis rate based on the stent and lumen diameters on follow-up angiography as a percentage of that immediately after CAS was evaluated. Results: Both the stent and lumen diameters were significantly dilated 12 months after CAS (p <0.001). There were no significant stent-type-related differences in the stent expansion rate. In the symptomatic stenosis group, this expansion rate was significantly higher than in the asymptomatic stenosis group (p = 0.02). With respect to the presence or absence of a high signal intensity on time of flight (TOF) magnetic resonance (MR) images, the stent expansion rate was significantly higher in the high signal intensity group (p = 0.006). In patients with a plaque/sternocleidomastoid muscle signal intensity ratio of ≥1.50 on plaque images, it was significantly higher than in those with a value of <1.50 (p = 0.006). However, there were no significant differences in the lumen expansion rate among the groups. Conclusion: Both the stent and vascular lumen were dilated 12 months after CAS. Plaque fragility influenced the stent expansion rate; however, there were no significant factor-related differences in the vascular lumen expansion rate.博士（医学）・乙第1414号・平成30年3月15日©2017 The Editorial Committee of Journal of Neuroendovascular Therapy. All rights reserved. This is an open access article distributed under the terms of Creative Commons Attribution License(CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/

Rapid Quantification of Bacteria in Infected Root Canals Using Fluorescence Reagents and a Membrane Filter: A Pilot Study on Its Clinical Application to the Evaluation of the Outcomes of Endodontic Treatment

Objective. The bacterial examination has been performed during the course of the root canal treatment. In the present pilot study, the new developed method, using fluorescence reagents and a membrane filter, was applied to the detection and quantification of bacteria in infected root canals, in order to evaluate the outcomes of the treatment. Methods. Six infected root canals with periapical lesions from 5 subjects were included. Informed consent was obtained from all subjects (age ranges, 23–79 years). Samples from infected root canals were collected at the beginning of the treatment (termed #25 First), the end of the first day of treatment (termed #55 First), and the next appointment day (termed #55 Second). Then, the bacterial count (CFU) was measured using fluorescence reagents (4′,6′-diamidino-2-phenylindole and propidium iodide) and the polycarbonate membrane filter by Bioplorer. Results. The mean ± SD of CFU in the sample of “#25 First” was (1.0 ± 1.4) × 105. As the root canal treatment progressed, the CFU decreased as 7.9 × 103 (#55 First) and 4.3 × 102 (#55 Second). Conclusion. In the present pilot study, rapid detection and quantification of bacteria in infected root canals were found to be successfully performed using fluorescence reagents and a membrane filter (Bioplorer analysis)

High Levels of Copper, Zinc, Iron and Magnesium, but not Calcium, in the Cerebrospinal Fluid of Patients with Fahr's Disease

Patients with marked calcification of the basal ganglia and cerebellum have traditionally been referred to as having Fahr's disease, but the nomenclature has been criticized for including heterogeneous etiology. We describe 3 patients with idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The former 2 patients showed severe calcification of the basal ganglia and cerebellum, and the latter patient showed severe calcification of the cerebellum. We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the involvement of metabolism of several metals and/or metal-binding proteins during the progression of IBSPDC. More numerous patients with IBSPDC should be examined in other races to clarify the common mechanism of the disease and to investigate the specific treatment

ゾレドロン酸を全身投与した卵巣摘出ラットにおける矯正的歯の移動と歯根吸収

長崎大学学位論文 [学位記番号]博（医歯薬）甲第612号 [学位授与年月日]平成25年9月19

Serum N

Background. The aim of this study is to evaluate the usefulness of serum N-glycan profiling for prognosis in hemodialysis patients. Methods. Serum N-glycan analysis was performed in 100 hemodialysis patients in June 2008 using the glycoblotting method, which allows high-throughput, comprehensive, and quantitative N-glycan analysis. All patients were longitudinally followed up for 5 years. To evaluate the independent predictors for prognosis, patients' background, blood biochemistry, and N-glycans intensity were analyzed using Cox regression multivariate analysis. Selected N-glycans and independent factors were evaluated using the log-rank test with the Kaplan-Meier method to identify the predictive indicators for prognosis. Each patient was categorized according to the number of risk factors to evaluate the predictive potential of the risk criteria for prognosis. Results. In total, 56 N-glycan types were identified in the hemodialysis patients. Cox regression multivariate analysis showed cardiovascular events, body mass index, maximum intima media thickness, and the serum N-glycan intensity of peak number 49 were predictive indicators for overall survival. Risk classification according to the number of independent risk factors revealed significantly poor survival by increasing the number of risk factors. Conclusions. Serum N-glycan profiling may have a potential to predict prognosis in patients undergoing hemodialysis

再灌流後急性心筋梗塞患者におけるリバースリモデリングと非造影T1低信号梗塞コア

Background: Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it. Methods and Results: We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month followup (hazard ratio: 0.087, 95% confidence interval: 0.017–0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. Conclusions: ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.博士（医学）・乙第1529号・令和5年3月15

A small number of abnormal brain connections predicts adult autism spectrum disorder

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum