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Overexpression of microRNA-542-3p attenuates the differentiating capacity of endometriotic stromal cells.
Get PDF埼玉医科大学博士（医学）平成29年度Endometriosis is defined as the presence of endometrial glandular and stromal cells outside of the uterine cavity. A previous study reported that microRNA (miR)-542-3p plays a critical role in eutopic endometrial decidualization. This study aims to clarify the potential role of miR-542-3p and the target gene,(insulin-like growth factor-binding protein 1), in the impairment of the decidualizing capacity of human ectopic endometrial stromal cells (HEcESCs).In vitro analysis of primary undifferentiated and decidualizing human eutopic endometrial stromal cells (HEuESCs) and HEcESCs was conducted. The primary HEuESCs or HEcESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate (8-bromo-cAMP) and medroxyprogesterone acetate (MPA).The morphological and biological differentiating capacities of the HEcESCs were markedly impaired. In contrast to the HEuESCs, the HEcESCs that were treated with the decidual stimulus retained the mesenchymal phenotype and capacity for migration. The down-regulation of miR-542-3p in the HEcESCs treatment with 8-bromo-cAMP and MPA was much weaker than that of the HEuESCs. High expression of miR-542-3p led to a significant decrease in the expression of IGFBP1 in the HEcESCs.Impairment of the differentiating capacity by the overexpression of miR-542-3p could influence the capacity for migration and invasion of endometriotic cells in an ectopic environment
The dose of direct oral anticoagulants and outcomes of intracerebral hemorrhage: Preliminary findings.
Get PDF埼玉医科大学博士（医学）平成30年度The effect of a direct-acting oral anticoagulant (DOAC) dose on intracerebral hemorrhage (ICH) severity and outcome remains unclear. The aim of this study is to clarify the frequency of off-label dosing of DOAC treatments in ICH patients and compare clinical characteristics.We studied 43 patients with ICH who were treated with DOAC for nonvalvular atrial fibrillation before the onset of ICH. DOAC treatments were categorized into three groups based on the following doses: optimal dose, under-dose, and overdose.Overall, 31 patients were optimally dosed, 10 were under-dosed, and 2 were overdosed. CHADSand CHADS-VASc scores were the highest in the overdose group (median, 4, 6, respectively) and the lowest in the optimal dose group (median, 2, 4, respectively) (p = 0.006, p = 0.005, respectively). ICH severity measured using the National Institutes of Health Stroke Scale scores was the highest in the overdose group (median, 26.5) and the lowest in the under-dose group (median, 6.5) (p = 0.244). Larger initial hematoma volume was observed in the overdose group. The ratio of good outcome (modified Rankin Scale score ≤ 2) was higher in the under-dose group (40%) than the other groups, but this difference was not significant.Our study shows only a few patients received overdosing of a DOAC before the onset of ICH, and they were associated with poorer functional outcomes. Conversely, under-dosing was associated with better functional outcomes than the other groups
Dynamic knee valgus alignment influences impact attenuation in the lower extremity during the deceleration phase of a single-leg landing.
Get PDF埼玉医科大学博士(医学)平成29年度Dynamic knee valgus during landings is associated with an increased risk of non-contact anterior cruciate ligament (ACL) injury. In addition, the impact on the body during landings must be attenuated in the lower extremity joints. The purpose of this study was to investigate landing biomechanics during landing with dynamic knee valgus by measuring the vertical ground reaction force (vGRF) and angular impulses in the lower extremity during a single-leg landing. The study included 34 female college students, who performed the single-leg drop vertical jump. Lower extremity kinetic and kinematic data were obtained from a 3D motion analysis system. Participants were divided into valgus (N = 19) and varus (N = 15) groups according to the knee angular displacement during landings. The vGRF and angular impulses of the hip, knee, and ankle were calculated by integrating the vGRF-time curve and each joint's moment-time curve. vGRF impulses did not differ between two groups. Hip angular impulse in the valgus group was significantly smaller than that in the varus group (0.019 ± 0.033 vs. 0.067 ± 0.029 Nms/kgm, p<0.01), whereas knee angular impulse was significantly greater (0.093 ± 0.032 vs. 0.045 ± 0.040 Nms/kgm, p<0.01). There was no difference in ankle angular impulse between the groups. Our results indicate that dynamic knee valgus increases the impact the knee joint needs to attenuate during landing; conversely, the knee varus participants were able to absorb more of the landing impact with the hip joint
A novel detection procedure for mutations in the 23S rRNA gene of Mycoplasma pneumoniae with peptide nucleic acid-mediated loop-mediated isothermal amplification assay.
Get PDF埼玉医科大学博士(医学)平成29年度Rapid and easy detection of a single nucleotide point mutation of bacterial genes, which is directly linked to drug susceptibility, is essential for the proper use of antimicrobial agents. Here, we established a detection method using a peptide nucleic acid mediated loop-mediated amplification (LAMP) assay for macrolide (ML)-susceptible Mycoplasma pneumoniae. This assay specifically detected the absence of missense mutations encoding the central loop of domain V in the gene encoding 23S rRNA, which can reduce the affinity for MLs and subsequently generate ML-resistant strains of M. pneumoniae. Reactions were performed at 62°C for 60min and targeted gene amplifications were detected by real-time turbidity with a turbidimeter and naked-eye inspection of a color change. The assay had an equivalent detection limit of 100.0fg of DNA with the turbidimeter and showed specificity against 54 types of pathogens, whereas amplification was completely blocked, even at 100.0pg of DNA per reaction, in the presence of point mutations at 2063A and 2064A. The expected LAMP products were confirmed through identical melting curves in real-time LAMP procedures. This method would be a simple and rapid protocol for single nucleotide polymorphism genotyping as point-of-care testing technology without amplification of the sequences carrying the point mutations 2063A and 2064A in ML-resistant M. pneumoniae strains
Effects of Memantine on Nitric Oxide Production and Hydroxyl Radical Metabolism during Cerebral Ischemia and Reperfusion in Mice.
Get PDF埼玉医科大学博士（医学）平成30年度BACKGROUND:
The purpose of this study was to investigate the effects of memantine on brain ischemia. Because we can measure nitric oxide (NO) production and hydroxyl radical metabolism continuously, we investigated the effect of memantine on NO production and hydroxyl radical metabolism in cerebral ischemia and reperfusion.
METHODS:
Memantine (25 µmol/kg) was administered intraperitoneally to 6 C57BL/6 mice 30 minutes before ischemia. Seven additional mice received no injection (controls). NO production and hydroxyl radical metabolism were continuously monitored using bilateral striatal microdialysis in vivo. Hydroxyl radical formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by occluding the common carotid artery bilaterally for 10 minutes. Levels of the NO metabolites nitrite (NO2-) and nitrate (NO3-) were determined using the Griess reaction. Survival rates of hippocampal CA1 neurons were calculated and 8-hydroxydeoxyguanosine (8-OHdG)-immunopositive cells were counted to evaluate the oxidative stress in hippocampal CA1 neurons 72 hours after the start of reperfusion.
RESULTS:
The regional cerebral blood flow was significantly higher in the memantine group than in the control group after reperfusion. Furthermore, the level of 2,3-dihydroxybenzoic acid was significantly lower in the memantine group than in the control group during ischemia and reperfusion. Levels of NO2- and NO3- did not differ significantly between the 2 groups. Although survival rates in the CA1 did not differ significantly, there were fewer 8-OHdG-immunopositive cells in animals that had received memantine than in control animals.
CONCLUSIONS:
These data suggest that memantine exerts partially neuroprotective effects against cerebral ischemic injury.
Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved
Communication Disparity Between the Bereaved and Others: What Hurts Them and What Is Unhelpful? A Nationwide Study of the Cancer Bereaved.
Get PDF埼玉医科大学博士（医学）平成30年度The importance of communication between the cancer bereaved and others has been emphasized, but little is known about the more problematic aspects of this communication such as "unhelpful communication."The aim of this study was to establish which types of communication are perceived by the bereaved to be unhelpful.We conducted a cross-sectional, anonymous, nationwide survey at 103 certified hospice facilities/palliative care units in Japan.A total of 630 (63%) bereaved responded. Over 60% of the bereaved experiencing such communication considered it to be unhelpful, with the most unhelpful communication being "They emphasized the positive aspects of death." Thirteen items related to communication were separated into two factors ("advice for recovery" and "comments on cancer") by factor analysis. "Comments on cancer" were more unhelpful to them and were more often provided by those around them. With regard to "advice for recovery," losing a spouse was a stronger predictor with a higher odds ratio for communication distress than losing a parent (odds ratio, 5.34; 95% CI, 1.63-17.57).A number of the bereaved have experienced unhelpful communication regarding advice on dealing with bereavement and cancer. To prevent putting an unnecessary burden on the bereaved with such unhelpful communication, it is essential to understand problematic aspects. Even when people have no intention of hurting the bereaved, some communication may do so. Communication with the bereaved is also a core clinical skill required by health professionals, and further efforts are required to support the grieving process
Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression.
Get PDF埼玉医科大学博士（医学）平成29年度Krebs von den Lungen-6 (KL-6), a mucinous sialylated sugar chain on human mucin-1 glycoprotein (MUC1), is a diagnostic marker for interstitial lung diseases. Furthermore, elevated serum KL-6 levels have been observed in certain malignant tumor types of epithelial origin. The expression of MUC1 has been observed in patients with epithelial ovarian cancer (EOC) and is considered a potential therapeutic target. In the present study, KL-6 serum levels were investigated in patients clinically suspected of having malignant ovarian tumors. A total of 219 patients were enrolled in the study, which analyzed their serum KL-6 levels in addition to tumor expression of MUC1 using immunohistochemistry. High serum KL-6 levels were predominantly observed in patients with EOC, and did not occur in patients with benign or borderline tumors. The level of serum KL-6 was highly correlated with tumor stage, grade and histological type, and demonstrated superior sensitivity for the detection of ovarian cancer compared with that of serum cancer antigen 125. High serum KL-6 was significantly associated with shorter progression-free survival. In addition, tumor MUC1 expression status was significantly correlated with serum KL-6 levels. These data suggest that serum KL-6 may be a useful, non-invasive biomarker surrogate for tumor MUC1 expression in future clinical trials of MUC1-targeted therapy