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81.
The epitopes for some antiphospholipid antibodies are adducts of oxidized phospholipid and β2 glycoprotein 1 (and other proteins) 下载免费PDF全文
Sohvi Hrkk Elizabeth Miller D. Ware Branch Wulf Palinski Joseph L. Witztum 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(19):10356-10361
Circulating autoantibodies to phospholipids (aPLs), such as cardiolipin (CL), are found in patients with antiphospholipid antibody syndrome (APS). We recently demonstrated that many aPLs bound to CL only after it had been oxidized (OxCL), but not to a reduced CL analogue that could not undergo oxidation. We now show that the neoepitopes recognized by some aPLs consist of adducts formed between breakdown products of oxidized phospholipid and associated proteins, such as β2 glycoprotein 1 (β2GP1). Addition of human β2GP1, polylysine, native low-density lipoprotein, or apolipoprotein AI to OxCL-coated wells increased the anticardiolipin antibody (aCL) binding from APS sera that first had been diluted so that no aCL binding to OxCL could be detected. No increase in aCL binding was observed when these proteins were added to wells coated with reduced CL. The ability of β2GP1, polylysine, or low-density lipoprotein to be a “cofactor” for aCL binding to OxCL was greatly reduced when the proteins were methylated. Incubation of β2GP1 with oxidized 1-palmitoyl-2-linoleyl-[1-14C]-phosphatidylcholine (PC), but not with dipalmitoyl-[1-14C]-PC, led to formation of covalent adducts with β2GP1 recognized by APS sera. These data suggest that the reactive groups of OxCL, such as aldehydes generated during the decomposition of oxidized polyunsaturated fatty acids, form covalent adducts with β2GP1 (and other proteins) and that these are epitopes for aCLs. Knowledge that the epitopes recognized by many aPLs are adducts of oxidized phospholipid and associated proteins, including β2GP1, may give new insights into the pathogenic events underlying the clinical manifestations of APS. 相似文献
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Rashid Khan Ashwani K Singal Bhupinderjit S Anand 《World journal of gastroenterology : WJG》2014,20(34):11935-11938
Alcohol abuse and chronic hepatitis C virus(HCV)infection are two major causes of chronic liver disease in the United States.About 10%-15%of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection.Data on outcomes on graft and patient survival,HCV recurrence,and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature.Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis.However,some other studies do not support these observations.However,most studies are limited to a retrospective design or small sample size.Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers. 相似文献
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Julie C. Sung Ciara Bosh Brooke Wyatt Mark Miller Alyson Harty David Del Bello Sterling Knight Douglas T. Dieterich Ponni V. Perumalswami Andrea D. Branch 《Journal of viral hepatitis》2020,27(4):350-359
Patient‐reported outcomes (PROs) are important measures of quality of life. Direct‐acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA‐based HCV cure on PROs and liver‐related outcomes in real‐world patients at a large urban medical center. The short form (SF)‐36 and three additional validated instruments were used. F3‐4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2‐3 steatosis was defined as > 270 dB/m by TE‐controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF‐36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0‐2 fibrosis and those with F3‐F4 fibrosis both improved in 22 domains. Patients with baseline S0‐S1 steatosis improved in more domains (23) than patients with S2‐S3 steatosis (19). At baseline, patients with F3‐F4 fibrosis and patients with S2‐3 steatosis had worse scores in certain PRO domains than patients with F0‐2 fibrosis or S0‐S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment. 相似文献
85.
Matthew S. L. Lee Bharat Ramakrishna Alan C. Moss Howard S. Gold Westyn Branch‐Elliman 《Transplant infectious disease》2020,22(1)
We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high‐risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life‐saving cure. The patient had subsequent clinical improvement, however, developed multidrug‐resistant Pseudomonas aeruginosa bacteremia 2 days post‐procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk. 相似文献
86.
脊柱结核并发HIV感染/AIDS患者因免疫功能低下,治疗的难度成倍增加。为规范脊柱结核并发HIV感染/AIDS患者的诊疗流程,使更多同行了解此类疾病治疗细节,并在治疗时有可靠依据,中国防痨协会骨关节结核专业分会、中国西部骨结核联盟、中国华北骨结核联盟、《中国防痨杂志》编辑委员会共同制定了《脊柱结核并发HIV感染/AIDS患者诊断及治疗专家共识》。本共识从脊柱结核并发HIV感染/AIDS患者的流行病学背景开始论述,对其常见临床表现、实验室检查、诊断标准、药物及手术治疗方法、手术治疗过程中的职业暴露和注意事项,以及研究方向等方面做了深入的阐述与讨论。 相似文献
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We tested human participants on a modified peak procedure in order to investigate the relation between interval timing and reward processing, and examine the interaction of this relation with three different dopamine-related gene polymorphisms. These gene polymorphisms affected the expression of catechol-o-methyltransferase, which catabolizes synaptic dopamine primarily in the prefrontal cortex (COMT Val158Met polymorphism), D2 dopamine receptors primarily in the striatum (DRD2/ANKK1-Taq1a polymorphism), and dopamine transporters, which clear synaptic dopamine in the striatum (DAT 3′ VNTR variant). The inclusion of these polymorphisms allowed us to investigate dissociable aspects of the dopamine system and their interaction with reward magnitude manipulations in shaping timed behavior. These genes were chosen for their roles in reward processing and cortico-striatal information processing that have been implicated for interval timing. Consistent with recent animal studies, human participants initiated their timed anticipatory responding earlier when expecting a larger reward in the absence of any changes in the timing of response termination or perceived time. This effect however was specific to two out of four evaluated COMT and DRD2 polymorphism combinations that lead to high prefrontal dopamine coupled with high D2 density and low prefrontal dopamine coupled with low D2 density. Larger rewards also decreased timing precision indices, some of which interacted with the COMT polymorphism. Furthermore, the COMT polymorphism that leads to higher prefrontal dopamine resulted in weaker manifestation of memory variability (relative to threshold variability) in timed behavior. There was no effect of DAT polymorphisms on any of the core behavioral measures. These results suggest that the reward modulates decision thresholds rather than clock speed, and that these effects are specific to COMT and DRD2 epistasis effects that presumably constitute a balanced prefrontal and striatal dopamine transmission. 相似文献
89.
Indran Davagnanam MB BCh BAO BMedSci FRCR Graeme Holland Raj S. Dattani Alexander Tamm Shashivadan P. Hirani MSc PhD CPsychol Nicky Kolfschoten MD Lisa Strycharczuk Cathy Green John S. Thornton PhD Alex Wright MB FRCP Mark Edsell FRCA Neil D. Kitchen MD FRCS David J. Sharp PhD Timothy E. Ham PhD Andrew Murray DPhil Cameron J. Holloway FRACP D.Phil Kieran Clarke PhD Mike P.W. Grocott BSc MBBS MD FRCA FRCP FFICM Birmingham Medical Research Expeditionary Society Caudwell Xtreme Everest Research Group 《Annals of neurology》2013,73(3):381-389
90.
Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach 下载免费PDF全文
Mark D. Wilkie MRCS DO‐HNS Navdeep S. Upile MRCS DO‐HNS Andrew S. Lau MRCS DO‐HNS Stephen P. Williams MRCS Jon Sheard FRCPath Tim R. Helliwell FRCPath Max Robinson FRCPath Jennifer Rodrigues FRCA Krishna Beemireddy FRCA Huw Lewis–Jones FRCR Rebecca Hanlon FRCR David Husband FRCR Aditya Shenoy FRCR Nicholas J. Roland FRCS Shaun R. Jackson FRCS Fazilet Bekiroglu FRCS Sankalap Tandon FRCS Jeffrey Lancaster FRCS Terence M. Jones FRCS 《Head & neck》2016,38(8):1263-1270