Time Variability of Nonthermal X-ray Stripes in Tycho's Supernova Remnant with Chandra

Analyzing Chandra data of Tycho's supernova remnant (SNR) taken in 2000, 2003, 2007, 2009, and 2015, we search for time variable features of synchrotron X-rays in the southwestern part of the SNR, where stripe structures of hard X-ray emission were previous found. By comparing X-ray images obtained at each epoch, we discover a knot-like structure in the northernmost part of the stripe region became brighter particularly in 2015. We also find a bright filamentary structure gradually became fainter and narrower as it moved outward. Our spectral analysis reveal that not only the nonthermal X-ray flux but also the photon indices of the knot-like structure change from year to year. During the period from 2000 to 2015, the small knot shows brightening of $\sim 70\%$ and hardening of $\Delta \Gamma \sim 0.45$. The time variability can be explained if the magnetic field is amplified to $\sim 100~\mathrm{\mu G}$ and/or if magnetic turbulence significantly changes with time.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in Ap

Raman spectroscopic detection of the T-HgII-T base pair and the ionic characteristics of mercury

Developing applications for metal-mediated base pairs (metallo-base-pair) has recently become a high-priority area in nucleic acid research, and physicochemical analyses are important for designing and fine-tuning molecular devices using metallo-base-pairs. In this study, we characterized the HgII-mediated T-T (T-HgII-T) base pair by Raman spectroscopy, which revealed the unique physical and chemical properties of HgII. A characteristic Raman marker band at 1586 cm−1 was observed and assigned to the C4=O4 stretching mode. We confirmed the assignment by the isotopic shift (18O-labeling at O4) and density functional theory (DFT) calculations. The unusually low wavenumber of the C4=O4 stretching suggested that the bond order of the C4=O4 bond reduced from its canonical value. This reduction of the bond order can be explained if the enolate-like structure (N3=C4-O4−) is involved as a resonance contributor in the thymine ring of the T-HgII-T pair. This resonance includes the N-HgII-bonded state (HgII-N3-C4=O4) and the N-HgII-dissociated state (HgII+ N3=C4-O4−), and the latter contributor reduced the bond order of N-HgII. Consequently, the HgII nucleus in the T-HgII-T pair exhibited a cationic character. Natural bond orbital (NBO) analysis supports the interpretations of the Raman experiments

HTLV-1 bZIP Factor Induces T-Cell Lymphoma and Systemic Inflammation In Vivo

Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL), and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (Treg). Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for Treg cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ), which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ Treg cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased Treg cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ Treg cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of Treg cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases

Amantadine can Ameliorate Lower Urinary Tract Dysfunction and Nocturnal Polyuria in Patients with Parkinson Disease and Vascular Parkinsonism

Background:Amantadine is a drug used for patients with Parkinson\u27s disease (PD) and vascular parkinsonism (VP). These patients often have lower urinary tract symptoms (LUTS) and nocturnal polyuria (NP). Thus, we investigated the effect of amantadine on these in parkinsonian patients.Methods:Twenty-two patients with LUTS, including 13 with PD and nine with VP, were recruited. We performed a urinary questionnaire, frequency-volume chart, and residual urine (RU) measurement before and after daily administration of 150 mg and 300 mg amantadine.Results:Before amantadine administration, mean daytime urinary frequency was 9.07(standard error [SE], 0.64), nighttime urinary frequency 2.89 (0.24), urinary urgency per week 24.2 (6.69), urge incontinence per month 15.1( 9.94), urine volume per void 145.6( 12.6) mL, and residual urine volume 12.5( 6.30) mL. After daily 150 mg amantadine administration, mean daytime and nighttime urinary frequency, urinary urgency, and urge incontinence decreased to 6.9( 0.42), 1.97( 0.21), 13.0( 3.58), and 14.2( 10.2), respectively, and urine volume per void increased to 174.1( 11.3) mL. NP( N=8) was ameliorated in six patients. No patient had side effects. After daily 300 mg amantadine administration( N=8), mean daytime and nighttimeurinary frequency, urinary urgency, and urge incontinence decreased to 6.90 (0.33), 1.69 (0.10), 5.88 (1.61), and 2.31 (0.61), respectively, and urine volume per void increased to180.2 (15.0) mL. NP (N=4) was ameliorated in two patients. One patient developed hallucination, and two patients developed flashing sensation.Conclusion:Amantadine has beneficial effects on LUTS and NP in patients with VP and PD

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

局所進行性膀胱癌に対するAngiotensin-II併用動脈内注入化学療法:単独施設における症例集積研究

臨床病期T2-T4NxM0の膀胱癌を有する患者に, cisplatin, pirarubicin, angiotensin-II(AT-II)を腫瘍栄養動脈より注入し, その治療効果を評価した.その結果, 1)臨床病期T2症例における5年および8年腫瘍特異的生存率は100%, 33%であり, T3-4症例ではそれぞれ63%, 63%であった.両群間に推計学的に有意差は認められなかった(P=0.445). 2)単変量および多変量解析では, 腫瘍数, 増殖型, 腫瘍の大きさが腫瘍特異的生存率と独立して相関傾向があったが, 推計学的有意差は認めなかった.以上, これらのことからも, AT-II併用動脈内注入化学療法は, 重篤な副反応や合併症を伴わず, 比較的良好な治療効果を有し, 局所進行性膀胱癌患者に対する有用な治療法と考えられたPatients with locally advanced bladder cancer are at significant risk for metastases. We aimed to evaluate the usefulness of intra-arterial chemotherapy (IAC) combined with angiotensin-II (AT-II) in such patients. The possibility of bladder preservation is also discussed. Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4NxM0). Cisplatin, pirarubicin, and AT-II were infused through the tumor-feeding arteries. Cause-specific survival was the end point. We enrolled 37 patients who were treated with neoadjuvant IAC and 5 patients with adjuvant IAC. There were 7 patients (16.7%) with pathological complete remission. Overall 5-year and 10-year survival rates of the patients were 61.3% and 47.7%, respectively. The 5-year cause-specific survival rate was 100% for the clinical T2 group and 63% for the T3-4 group, and the 8-year survival rate was 33% and 63%, respectively. There was no statistically significant difference between these two groups (P=0.445). Multivariable analysis using tumor number, pattern of growth, and tumor size seemed to independently correlate with cause-specific survival, but there were no significant differences. Our results suggest that intra-arterial chemotherapy combined with AT-II is a useful treatment for patients with locally advanced bladder cancer, since this modality achieves a favorable response rate without severe toxicity or mortality