過剰適応の生起メカニズムの解明 : 評価懸念とストレス認知に着目して

内容の要約広島大学(Hiroshima University)博士(心理学)Doctor of Philosophy in Psychologydoctora

Polypharmacy at admission prolongs length of hospitalization in gastrointestinal surgery patients

博士（医学）福島県立医科大

Peptide ligand screening of α-synuclein aggregation modulators by in silico panning

<p>Abstract</p> <p>Background</p> <p>α-Synuclein is a Parkinson's-disease-related protein. It forms aggregates <it>in vivo</it>, and these aggregates cause cell cytotoxicity. Aggregation inhibitors are expected to reduce α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines.</p> <p>Results</p> <p>We screened peptide ligands against α-synuclein by <it>in silico </it>panning, a method which we have proposed previously. In this study, we selected as the target a very hydrophobic region known as the amyloid-core-forming region. Since this region cannot be dissolved in water, it is difficult to carry out the <it>in vitro </it>screening of its peptide ligand. We carried out 6 rounds of <it>in silico </it>panning using a genetic algorithm and a docking simulation. After the <it>in silico </it>panning, we evaluated the top peptides screened <it>in silico </it>by <it>in vitro </it>assay. These peptides were capable of binding to α-synuclein.</p> <p>Conclusion</p> <p>We demonstrated that it is possible to screen α-synuclein-binding peptides by <it>in silico </it>panning. The screened peptides bind to α-synuclein, thus affecting the aggregation of α-synuclein.</p

The repeating dislodgement of an ASO device

Transcatheter closure with an Amplatzer Septal Occluder (ASO) has become the standard treatment for secundum atrial septal defect (ASD). However, this procedure is associated with complications, such as device dislodgement. A 52-year-old woman was admitted with exertional dyspnea. Transesophageal echocardiography showed an ASD involving a 29 mm defect. Calculated Qp/Qs was 5.6 and all the rims were > 5 mm, with the exception of the posterior rim, which was 3 mm. Transcatheter ASD closure with an ASO was performed under general anesthesia. During emergence from anesthesia, tachycardia developed and the ASO device became dislodged. Hemodynamic changes associated with the end of anesthetic administration were believed to have led to device dislodgement. In a second transcatheter ASD closure, a low dose of propofol and remifentanil was maintained during emergence from anesthesia to reduce hemodynamic changes. However, device dislodgement occurred with nonsustained ventricular tachycardia. Finally, surgical ASD closure was performed. The large defect size, high Qp/Qs, and rim deficiency may have predisposed to device dislodgement after transcatheter ASD closure with ASO. The risk of device dislodgement should be considered in advance of surgery and, in high-risk cases, the patient's cardiovascular status should be closely monitored

Electrochemical Impedance Spectroscopy on the Performance Degradation of LiFePO4/Graphite Lithium-Ion Battery Due to Charge-Discharge Cycling under Different C-Rates

Lithium-ion batteries (LIBs) using a LiFePO4 cathode and graphite anode were assembled in　coin cell form and subjected to 1000 charge-discharge cycles at 1, 2, and 5 C at 25 C. The performance　degradation of the LIB cells under di erent C-rates was analyzed by electrochemical impedance　spectroscopy (EIS) and scanning electron microscopy. The most severe degradation occurred at 2 C　while degradation was mitigated at the highest C-rate of 5 C. EIS data of the equivalent circuit model　provided information on the changes in the internal resistance. The charge-transfer resistance within　all the cells increased after the cycle test, with the cell cycled at 2 C presenting the greatest increment　in the charge-transfer resistance. Agglomerates were observed on the graphite anodes of the cells　cycled at 2 and 5 C; these were more abundantly produced in the former cell. The lower degradation　of the cell cycled at 5 C was attributed to the lowered capacity utilization of the anode. The larger cell　voltage drop caused by the increased C-rate reduced the electrode potential variation allocated to the　net electrochemical reactions, contributing to the charge-discharge specific capacity of the cells

WIDGET: System Performance and GRB Prompt Optical Observations

The WIDeField telescope for Gamma-ray burst Early Timing (WIDGET) is used for a fully automated, ultra-wide-field survey aimed at detecting the prompt optical emission associated with Gamma-ray Bursts (GRBs). WIDGET surveys the HETE-2 and Swift/BAT pointing directions covering a total field of view of 62 degree x 62 degree every 10 secounds using an unfiltered system. This monitoring survey allows exploration of the optical emission before the gamma-ray trigger. The unfiltered magnitude is well converted to the SDSS r' system at a 0.1 mag level. Since 2004, WIDGET has made a total of ten simultaneous and one pre-trigger GRB observations. The efficiency of synchronized observation with HETE-2 is four times better than that of Swift. There has been no bright optical emission similar to that from GRB 080319B. The statistical analysis implies that GRB080319B is a rare event. This paper summarizes the design and operation of the WIDGET system and the simultaneous GRB observations obtained with this instrument.Comment: 19 pages, 11 figures, Accepted to appear in PAS

Novel 3D Liquid Cell Culture Method for Anchorage-independent Cell Growth, Cell Imaging and Automated Drug Screening

Abstract Cells grown in three-dimensional (3D) cultures are more likely to have native cell-cell and cell-matrix interactions than in 2D cultures that impose mechanical constraints to cells. However, most 3D cultures utilise gel matrix which, while serving as a scaffold, limits application due to its solid and opaque nature and inconsistency in cell exposure to exogenous signals. In 3D culture without gel matrix, cells tend to adhere to each other and form clumps with necrotic zone at the centre, making them unsuitable for analyses. Here we report that addition of low-molecular-weight agar named LA717 to culture media allows cells to grow as dispersed clonal spheroids in 3D. LA717 maintains cells dispersed and settled to the bottom of the medium while keeping the medium clear with little additional viscosity, making it suitable for microscopic observation. Importantly, cancer spheroids formed in LA717-containing medium show higher sensitivity to anti-cancer drugs such as Trametinib and MK-2206 that are not as effective in 2D. Because of the small and consistent size of spheroids, cell viability and drug toxicity are readily detectable in automated imaging analysis. These results demonstrate that LA717 offers a novel 3D culture system with great in vivo reflection and practicality

Site-specific differences in T lymphocyte composition of the gastric mucosa after Helicobacter pylori eradication

In our earlier work, we revealed that inflammation of the lesser curvature of the gastric body and antrum could constitute independent risk factors for gastric cancer development, while inflammation of the greater curvature was not. The aims of this study were as follows: first, to reveal the differences between T lymphocyte populations of the gastric antrum and the greater and lesser curvatures of the gastric body in patients after Helicobacter pylori eradication; second, to analyze the correlation between the composition of the stomach-resident T lymphocytes and time from H. pylori eradication; and third, to evaluate the sex differences in T lymphocyte subsets after H. pylori eradication. To investigate site-specific differences in stomach-resident T lymphocytes after H. pylori eradication, we performed flow cytometry analysis on samples taken from the gastric antrum, greater curvature of the gastric body, and lesser curvature of the gastric body of 20 patients. We also analyzed the correlation between the composition of the stomach-resident T lymphocytes and the time from H. pylori eradication. The lymphocyte subsets of the antrum and lesser curvature of the body were similar. In contrast, compared to those in the greater curvature of the gastric body, CD4(+)/CD3(+) lymphocyte subsets (43.8 +/- 19.4% vs 31.7 +/- 14.6%) were elevated in the lesser curvature of the body, whereas CD8(+)/CD3(+) (67.1 +/- 21.3% vs 80.4 +/- 12.0%), CD7(+)/CD3(+) (91.2 +/- 4.6% vs 93.7 +/- 3.8%), CCR4(+)/CD3(+) (7.7 +/- 8.1% vs 10.4 +/- 7.0%), CD45RA(+)/CD3(+)CD4(+) (27.2 +/- 24.8% vs 39.5 +/- 20.8%), and CD45RA(+)/CD3(+)CD4(-) (14.2 +/- 11.1% vs 18.7 +/- 11.5) were lower. Linear regression analysis showed a negative correlation between the time after H. pylori eradication and CD4(+)/CD3(+) (P < .05, R-2 = 0.198). There were no significant differences between men and women with respect to the lymphocyte populations. These results indicate that there are site-specific differences in lymphocyte composition in the stomach after H. pylori eradication

A multi band study of the optically dark GRB 051028

Observations were made of the optical afterglow of GRB 051028 with the Lulin observatory's 1.0 m telescope and the WIDGET robotic telescope system. R band photometric data points were obtained on 2005 October 28 (UT), or 0.095-0.180 days after the burst. There is a possible plateau in the optical light curve around 0.1 days after the burst; the light curve resembles optically bright afterglows (e.g. GRB 041006, GRB 050319, GRB060605) in shape of the light curve but not in brightness. The brightness of the GRB 051028 afterglow is 3 magnitudes fainter than that of one of the dark events, GRB 020124. Optically dark GRBs have been attributed to dust extinction within the host galaxy or high redshift. However, the spectrum analysis of the X-rays implies that there is no significant absorption by the host galaxy. Furthermore, according to the model theoretical calculation of the Ly$\alpha$ absorption to find the limit of GRB 051028's redshift, the expected $R$ band absorption is not high enough to explain the darkness of the afterglow. While the present results disfavor either the high-redshift hypothesis or the high extinction scenario for optically dark bursts, they are consistent with the possibility that the brightness of the optical afterglow, intrinsically dark.Comment: 5page, 5 figures, 1 table, accepted for publication in PASJ Letter. PASJ styl