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61.
Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function 总被引:23,自引:0,他引:23 下载免费PDF全文
Zeng R Spolski R Finkelstein SE Oh S Kovanen PE Hinrichs CS Pise-Masison CA Radonovich MF Brady JN Restifo NP Berzofsky JA Leonard WJ 《The Journal of experimental medicine》2005,201(1):139-148
Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor gamma chain (gamma(c)), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-gamma production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R-/- mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15. 相似文献
62.
Willem W. Overwijk Allan Tsung Kari R. Irvine Maria R. Parkhurst Theresa J. Goletz Kangla Tsung Miles W. Carroll Chunlei Liu Bernard Moss Steven A. Rosenberg Nicholas P. Restifo 《The Journal of experimental medicine》1998,188(2):277-286
Many tumor-associated antigens are nonmutated, poorly immunogenic tissue differentiation antigens. Their weak immunogenicity may be due to “self”-tolerance. To induce autoreactive T cells, we studied immune responses to gp100/pmel 17, an antigen naturally expressed by both normal melanocytes and melanoma cells. Although a recombinant vaccinia virus (rVV) encoding the mouse homologue of gp100 was nonimmunogenic, immunization of normal C57BL/6 mice with the rVV encoding the human gp100 elicited a specific CD8+ T cell response. These lymphocytes were cross-reactive with mgp100 in vitro and treated established B16 melanoma upon adoptive transfer. To understand the mechanism of the greater immunogenicity of the human version of gp100, we characterized a 9-amino acid (AA) epitope, restricted by H-2Db, that was recognized by the T cells. The ability to induce specific T cells with human but not mouse gp100 resulted from differences within the major histocompatibility complex (MHC) class I–restricted epitope and not from differences elsewhere in the molecule, as was evidenced by experiments in which mice were immunized with rVV containing minigenes encoding these epitopes. Although the human (hgp10025–33) and mouse (mgp10025–33) epitopes were homologous, differences in the three NH2-terminal AAs resulted in a 2-log increase in the ability of the human peptide to stabilize “empty” Db on RMA-S cells and a 3-log increase in its ability to trigger interferon γ release by T cells. Thus, the fortuitous existence of a peptide homologue with significantly greater avidity for MHC class I resulted in the generation of self-reactive T cells. High-affinity, altered peptide ligands might be useful in the rational design of recombinant and synthetic vaccines that target tissue differentiation antigens expressed by tumors. 相似文献
63.
Chalmers RM; Howard RS; Wiles CM; Hirsch NP; Miller DH; Williams A; Spencer GT 《QJM : monthly journal of the Association of Physicians》1996,89(6):469-476
Twenty-nine patients with a neuronopathic or neuropathic disorder were
referred for assessment of respiratory insufficiency between 1978 and 1994.
Diagnoses included spinal muscular atrophy (6), chronic idiopathic
demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary
motor and sensory neuropathy (3) and a miscellaneous group (5). We also
describe seven patients with Guillain-Barre syndrome (GBS) who required
long-term ventilatory support for over 6 months to 7 years after the
initial illness. Respiratory insufficiency occurred as a consequence of
respiratory muscle weakness, impaired bulbar function and restrictive lung
defects. In some groups presentation was with progressive nocturnal
hypoventilation culminating in acute respiratory failure. Five patients
with GBS or chronic idiopathic demyelinating neuropathy were weaned from
ventilatory support up to 18 months after the initial illness. The
remaining 24 patients required continuous or nocturnal ventilatory support
using intermittent positive-pressure ventilation (13), negative pressure
ventilation (4), nasal-mask-delivered intermittent positive-pressure
ventilation (4), nasal-mask-delivered continuous positive-pressure
ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed
(1). None have been weaned from support after a period of ventilation
ranging from one month to 10 years. Eight patients have subsequently died.
相似文献
64.
Alyssa Izquierdo BS Franziska Plessow PhD Kendra R. Becker PhD Christopher J. Mancuso BS Meghan Slattery NP Helen B. Murray BA Andrea S. Hartmann PhD Madhusmita Misra MD MPH Elizabeth A. Lawson MD Kamryn T. Eddy PhD Jennifer J. Thomas PhD 《The International journal of eating disorders》2019,52(4):419-427
65.
Elissa M. Ozanne PhD rea Loberg Sherwood Hughes Christine Lawrence Brian Drohan MS Alan Semine MD Michael Jellinek MD Claire Cronin MD Frederick Milham MD MBA Dana Dowd RN NP Caroline Block MD Deborah Lockhart John Sharko MS Georges Grinstein PhD Kevin S. Hughes MD 《The breast journal》2009,15(2):155-162
Abstract: Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective. 相似文献
66.
Rai NP 《中国医药工业杂志》2009,40(4)
醇或酚与2当量叔丁基溴在0.1当量碳酸铅催化下,35~45℃搅拌1~2.25h,得相应的叔丁基醚,14例收率75%~96%。 相似文献
67.
Yang S Cohen CJ Peng PD Zhao Y Cassard L Yu Z Zheng Z Jones S Restifo NP Rosenberg SA Morgan RA 《Gene therapy》2008,15(21):1411-1423
In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike gamma-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20-30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust anti-melanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy. 相似文献
68.
JK Gass SK Chan E Rytina DC Greenberg NP Burrows 《Journal of the European Academy of Dermatology and Venereology》2010,24(5):601-603
Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients. 相似文献
69.
Esther Abels Liron Pantanowitz Famke Aeffner Mark D Zarella Jeroen van der Laak Marilyn M Bui Venkata NP Vemuri Anil V Parwani Jeff Gibbs Emmanuel Agosto-Arroyo Andrew H Beck Cleopatra Kozlowski 《The Journal of pathology》2019,249(3):286-294
In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. 相似文献
70.
Jeff S. Healey MD Richard Merchant MD Chris Simpson MD Timothy Tang MD Marianne Beardsall MN/NP Stanley Tung MD Jennifer A. Fraser RN Laurene Long RN Janet M. van Vlymen MD Pirjo Manninen MD Fiona Ralley MBBCh Lashmi Venkatraghavan MD Raymond Yee MD Bruce Prasloski MD Shubhayan Sanatani MD Fran?ois Philippon MD 《Journal canadien d'anesthésie》2012,59(4):394-407