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11.
Eyad Elkord Deborah J. Burt Anette Sundstedt ?rjan Nordle Gunnar Hedlund Robert E. Hawkins 《Oncotarget》2015,6(6):4428-4439
Naptumomab estafenatox/ABR-217620/ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients'' peripheral blood. Levels of both Nap-specific CD4+ and CD8+ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects. 相似文献
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Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3− T cells expressing Helios (FoxP3−Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/−Helios+). We show that CD4+GARP+/−LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios− Tregs upon TCR stimulation. Unlike FoxP3+Helios− Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios− Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction. 相似文献
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Eyad Alsaeed 《Saudi Journal Of Gastroenterology》2009,15(4):268-270
Systemic lupus erythematosus (SLE) is associated with major gastrointestinal complications due to radiotherapy. A patient with active SLE and grade 4 nephropathy presented with inoperable advanced cancer of the cervix which proved to be contraindicated for chemotherapy. The patient was treated with intensity-modulated radiotherapy technique (IMRT). The patient, however, did not experience severe radiotherapy-related complications as expected with conventional techniques of radiotherapy. The tolerance of SLE patients to radiotherapy can thus be achieved by proper delivery of radiation and the sparing of normal tissues by IMRT although further confirmatory studies are required. 相似文献
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Eyad Almallouhi Sami Al Kasab Jillian B. Harvey Christopher Reardon Ali Alawieh Tarun Girotra Patricia Aysse Raymond D. Turner Christine A. Holmstedt 《Journal of stroke and cerebrovascular diseases》2019,28(1):185-190
Objective
To assess the long-term functional outcome of stroke in patients treated with mechanical thrombectomy (MT) performed during work hours (on-hours) versus after-hours, weekends, and official holidays (off-hours).Methods
Data on all patients receiving MT at a comprehensive stroke center was collected between December 2014-December 2016. Our primary outcomes were the discharge and 90-day modified Rankin Scale (mRS). We developed propensity scores for off-hours treatment and used inverse probability of treatment weights to address confounding. We estimated logistic regression to assess the relationship between off-hours treatment and favorable patient outcomes. Independent variables include receiving thrombectomy during the off-hours, admission National Institute of Health Stroke Scale (NIHSS), door to groin time in minutes, age, and race.Results
During the study period, 80 (41%) patients underwent thrombectomy during on-hours and 116 (59%) during off-hours. Mean age was 69.1 years for the on-hours group and 64.1 years for the off-hours group (P?=?.02). There were no statistically significant differences in median admission NIHSS, rate of alteplase administration, mean time from last known well to thrombectomy, rate of revascularization, and rate of hemorrhagic transformation between the 2 groups. Logistic regression analysis showed the probability of a favorable outcome at discharge (mRS ≤ 2) is 12.6 % lower for off-hours patients (P?=?.038, [95%CI ?.25 to ?.01]). For patients with a 90-day mRS (n?=?117), the probability of a favorable outcome was 18.7% lower for those treated during the off-hours (P?=?.029, [95%CI ?.36 to ?.02]).Conclusions
There is a higher probability of a good functional outcome in acute ischemic stroke patients who receive MT when performed during regular work hours. 相似文献16.
Mario Ricciardi Delia Franchini Carmela Valastro Stefano Ciccarelli Francesco Caprio Abu Eyad Assad Antonio Di Bello 《Anatomical record (Hoboken, N.J. : 2007)》2019,302(9):1658-1665
Multidetector computed tomographic (CT) anatomy was used to evaluate the lungs of 10 loggerhead sea turtle (Caretta caretta) without pulmonary disease, in order to provide a baseline of turtle lung anatomy by CT imaging. In all patients, in this retrospective anatomic study, the CT datasets were carefully evaluated for assessment of the bronchial tree morphology and branching pattern, of the arborization pattern of pulmonary arteries and veins and of the bronchoarterial–bronchovenous diameter ratios. Imaging anatomy was compared with previous published data based on dissection and microscopic anatomy. With the increasing availability of advanced imaging tools for wildlife animal patients, a detailed CT anatomy background is required to decipher correctly the pathologic respiratory conditions of sea turtles. Anat Rec, 302:1658–1665, 2019. © 2018 American Association for Anatomy 相似文献
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Eyad M Mallah Mohammad F Hamad Mays A ElManaseer Nidal A Qinna Nasir M Idkaidek Tawfiq A Arafat Khalid Z Matalka 《BMC clinical pathology》2011,11(1):1-6
Background
Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults.Methods
Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.Results
Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems.Conclusions
These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress. 相似文献19.
Khan S Burt DJ Ralph C Thistlethwaite FC Hawkins RE Elkord E 《Clinical immunology (Orlando, Fla.)》2011,138(1):85-96
Cytotoxic T Lymphocyte Antigen 4 (CTLA4) blockade has shown antitumor activity against common cancers. However, the exact mechanism of immune mediation by anti-CTLA4 remains to be elucidated. Further understanding of how CTLA4 blockade with tremelimumab mediates immune responses may allow a more effective selection of responsive patients. Our results show that tremelimumab enhanced the proliferative response of T effector cells (Teff) upon TCR stimulation, and abrogated Treg suppressive ability. In the presence of tremelimumab, frequencies of IL-2-secreting CD4(+) T cells and IFN-γ-secreting CD4(+) and CD8(+) T cells were increased in response to polyclonal activation and tumor antigens. Importantly, Treg frequency was not reduced in the presence of tremelimumab, and expanded Tregs in cancer patients treated with tremelimumab expressed FoxP3 with no IL-2 release, confirming them as bona fide Tregs. Taken together, this data indicates that tremelimumab induces immune responses mainly by direct activation of Teff rather than by affecting Tregs. 相似文献
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Eyad A.L. Thenayan MD Martin Savard Michael D. SharpeLoretta Norton BSc Bryan Young 《Journal of critical care》2010