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Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis
( Ashwin D. Dhanda ),( Euan Yates ),( Lauren P. Schewitz-bowers ),( Philippa J. Lait ),( Richard W. J. Lee ),( Matthew E. Cramp ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2020 Gut and Liver Vol.14 No.2
Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve short-term survival but nonresponders have the worst outcomes. There is a clinical need to identify these high-risk individuals at the time of presentation. T cells are implicated in AH and steroid responsiveness. We measured ex vivo T cell cytokine expression as a candidate biomarker of outcomes in patients with AH. Consecutive patients (bilirubin >80 μmol/L and ratio of aspartate aminotransferase to alanine aminotransferase >1.5 who were heavy alcohol consumers with discriminant function [DF] ≥32), were recruited from University Hospitals Plymouth NHS Trust. T cells were obtained and stimulated ex vivo. Cytokine expression levels were determined by flow cytometry and protein multiplex analysis. Twenty-three patients were recruited (10 male; median age 51 years; baseline DF 67; 30% 90-day mortality). Compared to T cells from nonsurvivors at day 90, T cells from survivors had higher baseline baseline intracellular interleukin (IL)-10:IL-17A ratio (0.43 vs 1.20, p=0.02). Multiplex protein analysis identified interferon γ (IFNγ) and tumor necrosis factor-α (TNF-α) as independent predictors of 90-day mortality (p=0.04, p=0.01, respectively). The ratio of IFNγ to TNF-α was predictive of 90-day mortality (1.4 vs 0.2, p=0.03). These data demonstrate the potential utility of T cell cytokine release assays performed on pretreatment blood samples as biomarkers of survival in patients with severe AH. Our key findings were that intracellular IL-10:IL-17A and IFNγ:TNF-α in culture supernatants were predictors of 90-day mortality. This offers the promise of developing T cell-based diagnostic tools for risk stratification. (Gut Liver 2020;14:265-268)
Miller, E. K.,Chung, K. Y.,Hutcheson, J. P.,Yates, D. A.,Smith, S. B.,Johnson, B. J. Oxford University Press 2012 Journal of animal science Vol.90 No.4
<P>We predicted that zilpaterol hydrochloride (ZH), a β-adrenergic receptor (AR) agonist, would depress mRNA and protein abundance of β-AR in bovine satellite cells. We also predicted that ZH would decrease total lipid synthesis in bovine adipose tissue. Bovine satellite cells isolated from the semimembranosus muscle were plated on tissue culture plates coated with reduced growth factor matrigel or collagen. Real-time quantitative PCR was used to measure specific gene expression after 48 h of ZH exposure in proliferating satellite cells and fused myoblasts. There was no effect of ZH dose on [(3)H]thymidine incorporation into DNA in proliferating myoblasts. Zilpaterol hydrochloride at 1 ?M decreased (P < 0.05) β1-AR mRNA, and 0.01 and 1 ?M ZH decreased (P < 0.05) β2-AR and β3-AR mRNA in myoblasts. The expression of IGF-I mRNA tended to increase (P = 0.07) with 1 ?M ZH. There was no effect (P > 0.10) of ZH on the β-AR or IGF-I gene expression in fused myotube cultures at 192 h or on fusion percentage. The β2-AR antagonist ICI-118, 551 at 0.1 ?M attenuated (P < 0.05) the effect of 0.1 ?M ZH to reduce expression of β1- and β2-AR mRNA. The combination of 0.01 ?M ZH and 0.1 ?M ICI-118, 551 caused an increase (P < 0.05) in β1-AR gene expression. There was no effect (P > 0.10) of ICI-118, 551 or ZH on β3-AR or IGF-I. Western blot analysis revealed that the protein content of β2-AR in ZH-treated myotube cultures decreased (P < 0.05) relative to control. Total lipid synthesis from acetate was increased by ZH in bovine subcutaneous adipose tissue explants in the absence of theophylline but was decreased by ZH when theophylline was included in the incubation medium. These data indicate that ZH alters mRNA and protein concentrations of β-AR in satellite cell cultures, which in turn could affect responsiveness of cells to prolonged ZH exposure in vivo. Similar to other β-adrenergic agonists, ZH had only modest effects on lipid metabolism in adipose tissue explants.</P>
Degradation of thin carbon-backed lithium fluoride targets bombarded by 68 MeV 17O beams
김용현,Davids B.,Williams M.,Hudson K.H.,Upadhyayula S.,Alcorta M.,Machule P.,Esker N.E.,Griffin C.J.,Williams J.,Yates D.,Lennarz A.,Angus C.,Hackman G.,김동건,J. Son,Park J.,Pak K.,김용균 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.3
To analyze the cause of the destruction of thin, carbon-backed lithium fluoride targets during a measurement of the fusion of 7Li and 17O, we estimate theoretically the lifetimes of carbon and LiF films due to sputtering, thermal evaporation, and lattice damage and compare them with the lifetime observed in the experiment. Sputtering yields and thermal evaporation rates in carbon and LiF films are too low to play significant roles in the destruction of the targets.We estimate the lifetime of the target due to lattice damage of the carbon backing and the LiF film using a previously reported model. In the experiment, elastically scattered target and beam ions were detected by surface silicon barrier (SSB) detectors so that the product of the beam flux and the target density could be monitored during the experiment. The areas of the targets exposed to different beam intensities and fluences were degraded and then perforated, forming holes with a diameter around the beam spot size. Overall, the target thickness tends to decrease linearly as a function of the beam fluence. However, the thickness also exhibits an increasing interval after SSB counts per beam ion decreases linearly, extending the target lifetime. The lifetime of thin LiF film as determined by lattice damage is calculated for the first time using a lattice damage model, and the calculated lifetime agrees well with the observed target lifetime during the experiment. In experiments using a thin LiF target to induce nuclear reactions, this study suggests methods to predict the lifetime of the LiF film and arrange the experimental plan for maximum efficiency