•The cultured glial cell was observed by high-frequency ultrasound.•Reflection was interpreted into characteristic acoustic impedance along the beam.•Three-dimensional acoustic impedance profile was ...acquired.•Non-invasive observation of intra-cellar structure was realized.
The acoustic microscope is a powerful tool for the observation of biological matters. Non-invasive in-situ observation can be performed without any staining process. Acoustic microscopy is contrasted by elastic parameters like sound speed and acoustic impedance. We have proposed an acoustic microscope that can acquire three-dimensional acoustic impedance profile. The technique was applied to cell-size observation. Glial cells were cultured on a 70 μm-thick polypropylene film substrate. A highly focused ultrasound beam was transmitted from the rear side of the substrate, and the reflection was received by the same transducer. An acoustic pulse, its spectrum spreading briefly 100 through 450 MHz, was transmitted. By analyzing the internal reflections in the cell, the distribution of characteristic acoustic impedance along the beam direction was determined. Three-dimensional acoustic impedance mapping was realized by scanning the transducer, exhibiting the intra-cellular structure including nucleus and cytoskeleton.
•We investigated valproic acid (VPA) neurodevelopmental toxicity in rats.•Excitability was assessed in postnatal synaptogenic-stage hippocampal slices.•Neural responses were first suppressed by GABA ...and then enhanced after eye opening.•VPA-exposed rats showed loss of early GABA inhibition of excitability.•VPA exposure promoted developmental excitability in the synaptogenic period.
Prenatal valproic acid (VPA) exposure is a well-known animal model of autism spectrum disorder (ASD) that produces alterations in embryonic and adult neurogenesis as well as adolescent/adulthood neurobehavioral phenotypes. However, the effects of prenatal VPA exposure on neural network excitability, especially during the synaptogenic period around eye opening, are not fully understood. In this study, we orally administered VPA (300 mg/kg) to pregnant Wistar rats on gestation day 15 and subsequently performed field potential recording in the CA1 area of hippocampal slices obtained from control (saline-exposed) and VPA-exposed rat pups between postnatal day (PND) 13 and PND18. In control slices, we observed an abrupt enhancement of stimulation-dependent responses including population spike (PS) amplitudes and field excitatory postsynaptic potential (fEPSP) slopes at PND16, which coincided with the average day of eye opening. In contrast, VPA-exposed pups exhibited delayed eye opening (PND17) and gradual rather than abrupt increases in PS amplitudes and fEPSP slopes over the duration of the synaptogenic period. We next investigated the involvement of ambient GABA (γ-aminobutyric acid) in PS generation using bicuculline methiodide (BMI), a GABA type A (GABAA) receptor antagonist. In control slices, BMI enhanced PS amplitudes during PND14–15 (before eye opening) and had little effect thereafter during PND16–17; a subsequent regression model analysis of BMI ratios (the ratio of PS amplitudes in the presence and absence of BMI) indicated a possible developmental change between these periods. In contrast, almost identical regression models were obtained for BMI ratios during PND14–15 and PND16–17 in the VPA-exposed group, indicating the absence of a developmental change. Our results suggest that prenatal VPA exposure accelerates the development of hippocampal excitability before eye opening. Moreover, our experimental model can be used as a novel approach for the evaluation of developmental neurotoxicity.
Background
Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer without intervention. We aim to examine the prognostic outcomes and risk ...factors for recurrence after laser vaporization for CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years.
Methods
Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors, and prognostic outcomes.
Results
The mean patient age was 34 years (range 18–64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN 2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was 18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard ratio HR, 1.028; 95% CI 1.005–1.051;
P
= 0.0167), body mass index (HR, 1.052; 95% CI 1.008–1.098;
P
= 0.0191), and glandular involvement (HR, 1.962; 95% CI 1.353–2.846;
P
= 0.0004).
Conclusions
Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However, patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence.
Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and ...safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively, especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.
FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c‐Myc, cyclin E, Notch and c‐Jun. FBXW7 is a known tumor‐suppressor gene, and mutations in FBXW7 have been reported ...in various human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes. We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBXW7 expression was negatively correlated with the malignant potential of ovarian tumors. That is to say, FBXW7 expression levels in ovarian cancer samples were significantly lower than those in borderline and benign tumors (P < 0.01). FBXW7 expression levels in serous carcinoma samples were the lowest among four major histological subtypes. In addition, p53‐mutated ovarian cancer samples showed significantly lower levels of FBXW7 expression compared with p53 wild‐type cancer samples (P < 0.001). DNA methylation arrays and bisulfite PCR sequencing experiments revealed that 5′‐upstream regions of FBXW7 gene in p53‐mutated samples were significantly higher methylated compared with those in p53 wild‐type samples (P < 0.01). This data indicates that p53 mutations might suppress FBXW7 expression through DNA hypermethylation of FBXW7 5′‐upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers, and was associated with p53 mutations and the DNA methylation status of the 5′‐upstream regions of FBXW7.
FBXW7 is a known tumor‐suppressor gene, and mutations in FBXW7 have been reported in various human malignancies. In this study, we found that the expression level of FBXW7 was correlated with the malignant potential of epithelial ovarian tumor other than mutational status of FBXW7. This is the first report that FBXW7 expression was downregulated in ovarian cancer and that p53 mutational status had an impact on the DNA methylation status of the 5′‐upstream regions of FBXW7.
•Singular value decomposition filter extracted the desired signals.•Reflected signals from substrate were suppressed using the proposed method.•The proposed method with tilt compensation was superior ...to without one.
Recently, a method for estimating three-dimensional acoustic impedance profiles in cultured cells and human dermal organs was proposed by interpreting the reflected ultrasonic signal based on a 1-D transmission line model for acoustic impedance microscopy (AIM). However, AIM has a disadvantage that reflected signals from cells overlap with that from a reference substrate. Additionally, the amplitudes of the reflected signals from the specimens are significantly weaker than that from the substrate. In this paper, we proposed a new method for separation of those signals based on a concept of clutter filter, which had been developed for a color Doppler method in medical ultrasonic imaging. The proposed filter using singular value decomposition (SVD) could separate original signals into desired signals such as those from the substrate and cells. Additionally, an effect from a tilt of the substrate was investigated in this study. Separability of the proposed filter was evaluated by two investigations. First one was to evaluate the separability by estimating a correlation coefficient between the filtered signal and signal reflected from a position only with the substrate. Second one was to compare a slope of the substrate estimated from the original signal with that estimated from the filtered signals from the substrate. The experimental results showed that the proposed filter could separate signals from the substrate, and the compensation of the tilt of the substrate could improve the performance of the proposed filter.
Weekly satellite sea surface height (SSH) anomaly data are used to clarify the mesoscale eddy characteristics in the lee of the island of Hawaii, the largest island in the Hawaiian Island chain. The ...lee eddy variability can be separated into two geographical regions. In the immediate lee southwest of Hawaii (Region E), eddy signals have a predominant 60 day period and a short life‐span, whereas in the region along 19°N west of ∼160°W (Region W), the eddy variability is dominated by 100 day signals and extends over a broad region. By applying a linear Ekman pumping model forced by the weekly QuikSCAT wind data, we find that the observed 60 day eddy signals originate in the southwest corner of Hawaii and are induced by the local 60 day wind stress curl variability associated with the blocking of the trade wind by the island of Hawaii. The relationship between the wind forcing and the observed SSH signals demonstrates the role of the ocean as an integrator that responds more effectively to the low‐frequency synoptic atmospheric forcing (∼60 days) than to the higher‐frequency forcing (∼30 days). Since the large‐amplitude 60 day SSH anomalies take 1–2 weeks to fully develop, it is possible that real‐time observed wind stress data can be used for the prediction of these anomalies. In contrast to the wind‐induced 60 day eddy signals in the lee of the island of Hawaii, the 100 day eddy signals in Region W are likely generated by the instability of the sheared North Equatorial Current and Hawaii Lee Countercurrent.
Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells ...(CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.
A 66-year-old man, who had undergone plasma exchange 30 years previously in Egypt for the treatment of falciparum malaria, was referred to our hospital for treatment of chronic hepatitis C (HCV). An ...analysis of the 655-nucleotide 5′-untranslated region-core region sequence revealed infection with HCV subtype 1g. A phylogenetic analysis of the full-length HCV genome confirmed that the patient's HCV was subtype 1g, which was the first case identified in Japan. Although his HCV possessed several naturally occurring resistance-associated substitutions in the nonstructural (NS) 3 and NS5A regions, he was successfully treated by combination therapy with glecaprevir/pibrentasvir.
We present the results of a multi-platform investigation that utilizes tracer information provided by the 2011 release of radioisotopes from the Fukushima Dai-ichi Nuclear Power Plant to better ...understand the pathways, mixing and transport of mode waters formed in the North Pacific Ocean. The focus is on transition region mode waters and radiocesium (137Cs and 134Cs) observations obtained from the May–June 2015 GO-SHIP occupation of the 152°W line in the Northeast Pacific. Samples include profiles from the surface to 1000 m and surface/subsurface pairs that provide an average 1° of latitude spacing along 152°W. We find a clear Fukushima (134Cs) signal from the surface to 400 m. The core signal (134Cs ∼10 Bq m-3, 137Cs ∼12 Bq m-3) at 41°-43°N lies at 30–220 m where mode waters formed through deep winter mixing in 2011 outcropped in the western North Pacific. The strongest 2015 152°W Fukushima-source radiocesium signal is associated with Dense-Central Mode Waters consistent with the densest variety of these mode waters being formed off the coast of Japan 4 years earlier. The radionuclide signal transited the basin along subsurface mode water isopycnals mainly on the northern side of the subtropical gyre before outcropping at and to the east of the 152°W line. In 2015, the densest 152°W waters with 134Cs lie at ∼435 m in the bottom range of Dense-Central Mode Water at 40°N. There is a weak, but detectable, signal in the boundary current off both Kodiak and Sitka. The deepest detectable 137Cs (weapon's testing background) are found at and to the north of 45°N at 900–1000 m. With the exception of a single subsurface sample near Hawaii, as of spring 2015, the southernmost 134Cs was found above 200 m at 30°N. A total date-corrected 134Cs inventory of 11–16 PBq is estimated. Qualitative comparison to model output suggests good consistency in terms of general location, latitudinal breadth, and predicted depth of penetration, allowing discussion of the bigger picture. However, the model's 2015 152°W radiocesium signal is quantitatively weaker and the core is offset in latitude, potentially due to the lack of consideration of atmospheric deposition.
•Northeast Pacific cesium observations highlight subsurface core of mode waters.•At 152°W, Fukushima cesium lies predominantly in Dense Central Model Waters.•Four-year old mode waters reach 400 m and Alaskan coast, but remain north of 30°N.•Northeast Pacific Fukushima cesium suggests total inventory of 11–16 PBq.•The Northeast Pacific fifty-year old weapon's testing signal reaches 1000 m.
PDF
