24 results on '"O'Brien, Rebecca"'
Search Results
2. X-ray diffraction stress analysis of interrupted titanium nitride films: Combining the sin2ψ and crystallite group methods
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Sinkovits, Theo, Zhao, Yue, O'Brien, Rebecca, and Dowey, Steve
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- 2014
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3. Mouse γδ T cells are capable of expressing MHC class II molecules, and of functioning as antigen-presenting cells
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Cheng, Lan, Cui, Yan, Shao, Hui, Han, Gencheng, Zhu, Ling, Huang, Yafei, O'Brien, Rebecca L., Born, Willi K., Kaplan, Henry J., and Sun, Deming
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- 2008
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4. The Notch-1 receptor in prostate tumorigenesis.
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O'Brien, Rebecca, Marignol, Laure, and O'Brien, Rebecca
- Abstract
The Notch signalling pathway plays a fundamental role in tissue development due to its involvement in cell fate determination and postnatal tissue differentiation. Its capacity to regulate cell growth and development has been linked to the occurrence of several cancers including that of the prostate. The transmembrane receptor Notch-1 of this pathway has been linked to the oncogenic role of Notch signalling in prostate adenocarcinoma. Other studies have suggested a tumour suppressive function for Notch-1. This review focuses on the role of Notch-1 in prostate cancer development and maintenance and relates this to the fundamental role of Notch in normal prostate development. The current understanding of the aberrant Notch signalling characteristic of prostate cancer is discussed, and recent therapeutic advances in this field are presented. [ABSTRACT FROM AUTHOR]
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- 2017
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5. Bariatric surgery results: reporting clinical characteristics and adverse outcomes from an integrated healthcare delivery system.
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Li, Robert A., Fisher, David P., Dutta, Sanjoy, O’Brien, Rebecca M., Ackerson, Lynn M., Sorel, Michael E., and Sidney, Stephen
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Background Limited data have been reported on bariatric surgery within a large, high-volume regional multicenter integrated healthcare delivery system. Objectives Review clinical characteristics and short- and intermediate-term outcomes and adverse events from a bariatric surgery program within an integrated healthcare delivery system. Setting Single high-volume, multicenter regional integrated healthcare delivery system. Methods Adult patients who underwent primary bariatric surgery during 2010–2011 were reviewed. Clinical characteristics, outcomes, and weight loss results were extracted from the electronic medical record. Results A total of 2399 patients were identified within the study period. The 30-day rates of clinical outcomes for Roux-en-Y gastric bypass (RYGB; n = 1313) and sleeve gastrectomy (SG; n = 1018) were 2.9% for readmission, 3.0% for major complications, .8% for reoperation, and 0% for mortality. One-year and 2-year weight loss results were as follows: percent weight loss (%WL) was 31.4 (±SD 8.5) and 34.2±12.0% for SG and 34.1±9.3 and 39.1±11.9 for RYGB; percent excess weight loss (%EBWL) was 64.2±18.0 and 69.8±23.7 for SG and 68.0±19.3 and 77.8±23.7 for RYGB; percent excess body mass index loss (%EBMIL) was 72.9±21.0 and 77.7±22.4 for SG and 76.6±22.1% and 85.6±21.6 for RYGB. Follow-up for each procedure at 1 year was 76% for SG (n = 778) and 80% for RYGB (n = 1052) and at 2 years was 65% for SG (n = 659) and 67% for RYGB (n = 875). Conclusions A large regional high-volume multicenter bariatric program within an integrated healthcare delivery system can produce excellent short-term results with low rates of short- and intermediate-term adverse outcomes. [ABSTRACT FROM AUTHOR]
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- 2015
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6. γδ T cells and Th17 cytokines in hypersensitivity pneumonitis and lung fibrosis.
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Simonian, Philip L., Roark, Christina L., Born, Willi K., O'Brien, Rebecca L., and Fontenot, Andrew P.
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Hypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by the repeated inhalation of aerosolized antigens. With chronic exposure to an inhaled antigen, patients are at risk of developing irreversible pulmonary fibrosis as well as an increased morbidity and mortality. Although αβ T cells have been shown to be important in the pathogenesis of HP, γδ T cells also accumulate in the bronchoalveolar lavage of patients with HP. γδ T cells represent a distinct lymphocyte subset, whose primary function is not well understood. In contrast to αβ T cells, γδ T cells recognize unprocessed antigens, such as those upregulated on injured or stressed epithelial cells. In a murine model of HP induced by exposure to the ubiquitous microorganism Bacillus subtilis, γδ T cells expressing the canonical Vγ6/Vδ1 T cell receptor were dramatically expanded in the lung. The predominant cytokines expressed by this γδ T-cell subset were T-helper 17 (Th17) cytokines that were critical for bacterial clearance and the resolution of lung inflammation. Th17-expressing γδ T cells are also expanded in other murine models of lung infection and inflammation, which suggests that these cells play a sentinel role in mucosal immunity. Thus, an increased understanding of γδ T cells that express Th17 cytokines in HP and other inflammatory lung diseases may lead to the development of novel therapeutic and clinical strategies that prevent the development of fibrotic lung disease. [Copyright &y& Elsevier]
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- 2009
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7. Gammadelta T cells and Th17 cytokines in hypersensitivity pneumonitis and lung fibrosis.
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Simonian PL, Roark CL, Born WK, O'Brien RL, Fontenot AP, Simonian, Philip L, Roark, Christina L, Born, Willi K, O'Brien, Rebecca L, and Fontenot, Andrew P
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Hypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by the repeated inhalation of aerosolized antigens. With chronic exposure to an inhaled antigen, patients are at risk of developing irreversible pulmonary fibrosis as well as an increased morbidity and mortality. Although alphabeta T cells have been shown to be important in the pathogenesis of HP, gammadelta T cells also accumulate in the bronchoalveolar lavage of patients with HP. gammadelta T cells represent a distinct lymphocyte subset, whose primary function is not well understood. In contrast to alphabeta T cells, gammadelta T cells recognize unprocessed antigens, such as those upregulated on injured or stressed epithelial cells. In a murine model of HP induced by exposure to the ubiquitous microorganism Bacillus subtilis, gammadelta T cells expressing the canonical Vgamma6/Vdelta1 T cell receptor were dramatically expanded in the lung. The predominant cytokines expressed by this gammadelta T-cell subset were T-helper 17 (Th17) cytokines that were critical for bacterial clearance and the resolution of lung inflammation. Th17-expressing gammadelta T cells are also expanded in other murine models of lung infection and inflammation, which suggests that these cells play a sentinel role in mucosal immunity. Thus, an increased understanding of gammadelta T cells that express Th17 cytokines in HP and other inflammatory lung diseases may lead to the development of novel therapeutic and clinical strategies that prevent the development of fibrotic lung disease. [ABSTRACT FROM AUTHOR]
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- 2009
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8. Oral Administration of Active Hexose Correlated Compound Enhances Host Resistance to West Nile Encephalitis in Mice.
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Wang, Shuhui, Welte, Thomas, Fang, Hao, Chang, Gwong-Jen J., Born, Willi K., O'Brien, Rebecca L., Sun, Buxiang, Fujii, Hajime, Kosuna, Ken-Ichi, and Wang, Tian
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WEST Nile fever ,WEST Nile virus ,HEXOSE phosphates ,ENCEPHALITIS ,IMMUNE response ,IMMUNOTHERAPY ,MICE - Abstract
West Nile virus (WNV) poses a serious threat to public health, especially to the elderly and the immuno-compromised. Neither vaccines nor treatments are available for humans. Active hexose correlated compound (AHCC) is an extract of Lentinula edodes of the Basidiomycete family of fungi rich in α-glucans. In this study, we evaluated the effect of AHCC on host susceptibility in the murine model of WNV infection. Mice orally administered with AHCC (600 mg/kg) every other day for 1 wk before and at d 1 and 3 postinfection were assessed using viremia levels, survival rate, and protective immunity. AHCC administration in young (6- to 8-wk-old) mice attenuated viremia and mortality following lethal WNV infection. WNV- specific gM and lgG production and γδ T cell expansion were also enhanced in these mice. Aged (21- to 22-mo-old) mice were more susceptible to WNV infection than young mice, partially due to the dysfunction of γδ T cell subsets. AHCC administration in aged mice enhanced the protective Vγ1
+ T cell response as well as WNV-specific lgG but not IgM antibodies production. AHCC administration in aged mice attenuated viremia levels but led to no difference in mortality rate. Overall, our data suggests that AHCC enhances protective host immune responses against WNV infection in young and aged mice. Dietary supplementation with AHCC may be potentially immunotherapeutic for WNV-susceptible populations. [ABSTRACT FROM AUTHOR]- Published
- 2009
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9. Avoiding repair, maintaining face: Responding to hard-to-interpret talk from people living with dementia in the acute hospital.
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Pilnick, Alison, O'Brien, Rebecca, Beeke, Suzanne, Goldberg, Sarah, and Harwood, Rowan
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HEALTH facilities , *CONVERSATION , *DEMENTIA patients , *COMMUNICATION , *CRITICAL care medicine , *PATIENT-professional relations - Abstract
People living with dementia (PLWD) are almost always admitted to the acute hospital for reasons unrelated to their dementia, finding themselves in the unfamiliar environment of a Health Care of Older Persons acute ward. The effect of this environment creates a challenge not just for a PLWD themselves, but also for the staff who care for them. Concerns have been raised by both policy makers and staff about the quality of communication between hospital staff and PLWD. Using conversation analysis, we examined 41 video recordings of healthcare professional (HCP)/PLWD interactions collected across three acute inpatient wards in a large teaching hospital in the UK. In this paper, we focus our analysis on hard-to-interpret talk (talk where there are problems in hearing, speaking and/or understanding), and the ways in which healthcare professionals respond to this. Repair of hard- to- interpret talk is common in ordinary interaction, but we find that HCPs in this setting use a range of approaches to avoid direct repair. These approaches are: the use of non-committal responses and continuers such as 'yeah' or nods; the use of repetitions or partial repetitions; responding to the emotional tone displayed in the PLWD's utterance; closing the current topic and shifting to the next; and treating the PLWD's talk as related to the task at hand. We suggest that the use of these approaches may be one way in which HCPs manage respecting the personhood of the PLWD, by preserving face and enabling a continuation of an interaction in which the PLWD can take an active part. Our paper provides an empirical demonstration of the high level of interactional skill involved in dementia care work. It also illustrates how these skills can be described and specified, and hence incorporated into the recommendations and tips that are produced for communication with PLWD. • Communication between people living with dementia and hospital staff can be challenging. • We focus on hard-to-interpret talk and how healthcare professionals respond to this. • Repair is common in ordinary interaction but appears to be avoided here. • Avoiding repair may help acknowledge the personhood of people living with dementia. • Skills demonstrated here can be described and specified, and are therefore trainable. [ABSTRACT FROM AUTHOR]
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- 2021
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10. When people living with dementia say 'no': Negotiating refusal in the acute hospital setting.
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O'Brien, Rebecca, Beeke, Suzanne, Pilnick, Alison, Goldberg, Sarah E, and Harwood, Rowan H
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COMMUNICATION , *COMMUNICATIVE competence , *CONVERSATION , *DEMENTIA patients , *HEALTH facility employees , *JOB satisfaction , *PSYCHOLOGICAL stress , *VIDEO recording , *PSYCHOSOCIAL factors , *PATIENT-centered care , *PATIENT autonomy - Abstract
A quarter of UK acute hospital beds are occupied by people living with dementia (PLWD). Concerns have been raised by both policy makers and carers about the quality of communication between hospital staff and PLWD. PLWD may experience communication impairments such as word finding difficulties, limited ability to construct coherent narratives and difficulties understanding others. Since much healthcare delivery occurs through talk, healthcare professionals (HCPs) and PLWD are likely to experience increased communication barriers. Consistent with this, HCPs report stress and reduced job satisfaction associated with difficulty communicating with PLWD. HCPs face these challenges whilst striving to deliver person-centred care, respecting the autonomy and wishes of the patient before them. However, best practice recommendations in the field tend not to be based on actual interactional evidence. This paper investigates recurring interactional difficulties around HCP requests to carry out health and social care tasks and subsequent reluctance or refusal on the part of PLWD. Using conversation analysis, we examined 41 video recordings of HCP/PLWD interactions collected across three acute inpatient wards. We identify both the nature of the refusals, and any mitigation offered, and explore the requests preceding them in terms of entitlement and contingency. We also explore the nature of HCP requests which precede PLWD agreement with a course of action. We conclude that several features of requests can be seen to precede acceptance, principally the use of higher entitlement requests, and the lowering of contingencies. Our findings underline the importance of examining the contextual interactional detail involved in the negotiation of healthcare, which here leads to an understanding of how design of HCP requests can impact on an important healthcare activity being carried out. They also emphasise the power of conversation analytic methods to identify areas of frequent interactional trouble in dementia care which have not previously been articulated. • Acute hospital staff need to make requests of their patients living with dementia (83). • Hospital patients living with dementia may refuse important requests in direct ways (85). • This creates a dilemma for staff wishing to deliver respectful and effective care (83). • Some forms of requesting made direct refusal more interactionally relevant (77). • High entitlement requests with lowered contingencies supported request acceptance (83). [ABSTRACT FROM AUTHOR]
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- 2020
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11. Should I stay or should I go? How healthcare professionals close encounters with people with dementia in the acute hospital setting.
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Allwood, Rebecca, Pilnick, Alison, O'Brien, Rebecca, Goldberg, Sarah, Harwood, Rowan H., and Beeke, Suzanne
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TREATMENT of dementia , *COMMUNICATION , *CONVERSATION , *CRITICAL care medicine , *HOSPITAL patients , *MEDICAL care , *MEDICAL personnel , *PATIENT-professional relations , *MEDICAL protocols , *PATIENTS , *VIDEO recording , *PATIENT-centered care - Abstract
Around a quarter of hospital beds in the UK are occupied by patients living with dementia (PWD), and communication impairments are common across all types of dementia, often exacerbated by the hospital environment. Unsurprisingly, healthcare professionals (HCPs) report particular challenges in caring for this patient group, whilst trying to recognise and value their personhood as per the underpinning ethos of person-centred care. However, whilst there is a growing body of research that underlines the importance of communication in dementia care, there is far less that actually examines this communication in real time interaction. Suggestions and pointers for good communication do exist, but these do not tend to be empirically derived, and sometimes conflict with empirical findings. This paper focuses on a specific area of interaction which has previously received very little attention: the way in which healthcare encounters are ended or closed. There is potentially a conflict between a pressure to manage a patient as efficiently as possible, and endeavouring to ensure person-centred care and deal with communication difficulties arising from dementia. Using conversation analysis, we examined forty-one video recordings of HCP/PWD interactions collected from an acute inpatient ward. We identify three phenomena around which there were recurring troubles in our dataset: ‘open-ended pre-closings’, ‘mixed messages’ and ‘non specifics and indeterminate terms’. We conclude that moves towards closing an encounter that appear intuitive to HCPs as competent interactants, and that may represent best practice in other healthcare settings, may in fact serve to confuse a PWD and create difficulties with closings. Our findings underline the importance of examining best practice guidance as it is actually talked into being, using approaches which can unpack the interactional detail involved. They also emphasise the importance of context in the analysis of healthcare delivery, to avoid a ‘one size fits all’ approach. [ABSTRACT FROM AUTHOR]
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- 2017
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12. X-ray diffraction stress analysis of interrupted titanium nitride films: Combining the sin2ψ and crystallite group methods.
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Sinkovits, Theo, Zhao, Yue, O'Brien, Rebecca, and Dowey, Steve
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TITANIUM nitride films , *X-ray diffraction , *STRAINS & stresses (Mechanics) , *METAL microstructure , *PHYSICAL vapor deposition , *CRYSTAL growth , *THICKNESS measurement - Abstract
Abstract: Interruptions during film growth have been discussed by researchers to assist in understanding the evolution of stress in physical vapour deposition films. A change in intrinsic stress is directly related to microstructure, hence careful analysis of stress in films can provide valuable structure–stress correlated information. In this study we discuss the use of combining two X-ray diffraction (XRD) stress analysis methods to elucidate the effect of interruptions during growth on the residual stress of TiN films. The sin2ψ and crystallite group method (CGM), scanning the (220) peaks from all grains in the film and only (111) oriented crystallites respectively, were used to analyse residual stress in standard and interrupted cathodic arc TiN films 1.5, 3.5 and 6.5μm thick, grown on high-speed steel substrates. The sin2ψ method does not reveal any changes in stress with interruptions, however, measurements using the CGM show increased compressive stress and increased a0 in the resultant TiN films. A comparison of results from both XRD methods indicates that an increased compressive stress from interruptions could be due to an increased number of defects in (111) oriented grains during the interruptions which would also affect a0 as evident. In both methods, compressive stresses are found to decrease with increased thickness of films. [Copyright &y& Elsevier]
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- 2014
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13. A Unique Vγ5-T-cell population in the murine mammary gland
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Reardon, Christopher, Born, Willi K., and O’Brien, Rebecca L.
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T cells , *CELL membranes , *CELL receptors , *MONOCLONAL antibodies - Abstract
Abstract: Mammary epithelia and the epidermis share a common embryologic origin. Like resident epidermal T cells (ETC), a significant number of murine mammary gland T cells (MTC) express Vγ5-T-cell receptors (TCR). MTC were assessed to see if they express the same invariant Vγ5/Vδ1-TCRs as those of ETC. MTC-derived hybridomas, positive for Vγ5-TCRs, expressed Vδ5 instead of Vδ1. Additionally, they showed non-germline additions in the γ-TCR and δ-TCR junctions, sharing among them an identical 19-nucleotide N-region in the δ-TCR junctions. Vγ5-TCR and Vδ5-TCR gene sequences from fresh peripartum MTC also contained variable N-regions, including a 7-nucleotide N-region similar to one found in the hybridomas. Thus, Vγ5-TCR+ MTC are distinct from Vγ5-TCR+ ETC by expressing variable non-canonical TCRs, predicting differences in the two T-cell populations in ligand specificity and in function. [Copyright &y& Elsevier]
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- 2006
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14. The function of γδ T cells in innate immunity
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Born, Willi K, Reardon, Christopher L, and O’Brien, Rebecca L
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T cells , *NATURAL immunity , *IMMUNE system , *T cell receptors - Abstract
Many researchers believe that γδ T lymphocytes belong somewhere ‘in-between’ the innate and adaptive immune systems. Recent studies strongly emphasize the innate features and functions of these cells, including the use of germline elements of the T cell receptor for ligand recognition, segregation into functionally specialized cell populations in correlation with T cell receptor variable gene or protein expression, interactions with cells of the innate system at many levels and, the latest addition, the ability to present antigen. Thus, at present, much evidence suggests that γδ T cells function in an innate manner, although they are arguably the most complex and advanced cellular representatives of the innate immune system. [Copyright &y& Elsevier]
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- 2006
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15. Dual functions of murine γδ cells in inflammation and autoimmunity in coxsackievirus B3-induced myocarditis: role of Vγ1+ and Vγ4+ cells
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Huber, S.A., Born, Willi, and O’Brien, Rebecca
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COXSACKIEVIRUSES , *CARDIOMYOPATHIES , *APOPTOSIS , *DEFENSE reaction (Physiology) - Abstract
Abstract: Coxsackieviruses are a cause of clinical myocarditis. Both virus replication and host defense mechanisms, including virus-induced autoimmunity, mediate heart injury and cardiac dysfunction. Vγ4+ cells kill infected cardiocytes and virus-specific CD4+ Th2 cells through Fas-dependent apoptosis and CD1d. The CD4+ Th1 response is necessary for activation of the autoimmune CD8+ T cells, which kill uninfected cardiocytes through perforin-dependent mechanisms. [Copyright &y& Elsevier]
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- 2005
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16. γδ T cells recognize the insulin B:9–23 peptide antigen when it is dimerized through thiol oxidation.
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Kemal Aydintug, M., Zhang, Li, Wang, Chao, Liang, Dongchun, Wands, J.M., Michels, Aaron W., Hirsch, Brooke, Day, Brian J., Zhang, Gongyi, Sun, Deming, Eisenbarth, George S., O’Brien, Rebecca L., and Born, Willi K.
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T cells , *INSULIN , *PEPTIDES , *ANTIGENS , *SULFHYDRYL group , *DIMERIZATION , *TYPE 1 diabetes - Abstract
Highlights: [•] Gamma delta T cells specifically respond to the insulin peptide B:9–23. [•] The response requires dimerization of the peptide via thiol oxidation. [•] The oxidized dimeric peptide adopts a distinct secondary structure. [•] This secondary structure appears to be required for the gamma delta response. [Copyright &y& Elsevier]
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- 2014
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17. Vγ1+ γδ T cells reduce IL-10-producing CD4+CD25+ T cells in the lung of ovalbumin-sensitized and challenged mice
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Hahn, Youn-Soo, Ji, Xu Yin, Woo, Sung-Il, Choi, Young-Ki, Song, Min-Seok, Shin, Kyung-Seop, Jin, Niyun, O’Brien, Rebecca L., and Born, Willi K.
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INTERLEUKIN-10 , *T cells , *LABORATORY mice , *CD4 antigen , *CELL differentiation , *LUNGS , *CYTOKINES - Abstract
Abstract: In OVA-sensitized and challenged mice, γδ T cells expressing Vγ1 enhance airway hyperresponsiveness (AHR) but the underlying mechanism is unclear. These cells also reduce IL-10 levels in the airways, suggesting that they might function by inhibiting CD4+CD25+ regulatory T cells (Treg) or other CD4+ T cells capable of producing IL-10 and suppressing AHR. Indeed, sensitization and challenge with OVA combined with inactivation of Vγ1+ cells increased CD4+CD25+ cells in the lung, and markedly those capable of producing IL-10. The cellular change was associated with increased IL-10 and TGF-β levels in the airways, and a decrease of IL-13. Treg include naturally occurring Foxp3+ Treg, inducible Foxp3− Treg, and antigen-specific Treg many of which express folate receptor 4 (FR4). Although Foxp3 gene expression in the lung was also increased pulmonary CD4+ T cells, expressing Foxp3-protein or FR4 remained stable. Therefore, the inhibition by Vγ1+ γδ T cells might not be targeting Foxp3+ Treg but rather CD4+ T cells destined to produce IL-10. [Copyright &y& Elsevier]
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- 2008
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18. γδ T cells: an important source of IL-17
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Roark, Christina L, Simonian, Philip L, Fontenot, Andrew P, Born, Willi K, and O’Brien, Rebecca L
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T cells , *INTERLEUKINS , *CYTOKINES , *BACTERIAL diseases - Abstract
IL-17 is a cytokine that plays an important role in orchestrating innate immune function. In addition, IL-17 has been shown to exacerbate autoimmune diseases. CD4+ αβ T cells, γδ T cells, and NK cells all produce IL-17. Th17 cells are a newly defined αβ+ T cell lineage characterized by IL-17 production. However, γδ T cells are often the major source of this cytokine. Their response can be very rapid during bacterial infections and has been shown to be protective, but IL-17-producing γδ T cells have also been found to exacerbate collagen-induced arthritis. Interestingly, some γδ T cells produce IL-17 in response to IL-23 alone, even in naïve animals, suggesting they are already differentiated and may develop differently than CD4+ αβ Th17 cells. [Copyright &y& Elsevier]
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- 2008
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19. Macrophages express multiple ligands for γδ TCRs
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Aydintug, M. Kemal, Roark, Christina L., Chain, Jennifer L., Born, Willi K., and O’Brien, Rebecca L.
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LYMPHOCYTES , *LEUCOCYTES , *B cells , *CELL-mediated lympholysis - Abstract
Abstract: As only a handful of ligands have been identified, the general nature of the ligands recognized by γδ T cells remains unresolved. In this study, soluble multimerized γδ T cell receptors (smTCRs) representing the TCRs of two γδ T cell subsets common in the mouse were used to detect and track their own ligands. Ligands for both subsets were found on resident peritoneal macrophages taken from untreated mice, and the expression of both was further induced by Listeria monocytogenes infection. Nevertheless, the two types of ligand differ from one another in abundance, in the kinetics of their induction following Listeria infection, and in their ability to be induced by in vitro culture with lipopolysaccharide (LPS). Surprisingly, because both are detectable on normal macrophages, these host-derived ligands are likely expressed constitutively, but are induced to higher levels of expression by stress or inflammation. In contrast to T22 and other known cell surface ligands for γδ T cells in mice and humans, expression of these smTCR-defined ligands does not depend on β2-microglobulin, suggesting that they are not MHC class I or class I-like molecules. [Copyright &y& Elsevier]
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- 2008
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20. Accumulation of gamma/delta T cells in the lungs and their roles in neutrophil-mediated host defense against pneumococcal infection
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Nakasone, Chikara, Yamamoto, Natsuo, Nakamatsu, Masashi, Kinjo, Takeshi, Miyagi, Kazuya, Uezu, Kaori, Nakamura, Kiwamu, Higa, Futoshi, Ishikawa, Hiromichi, O'Brien, Rebecca L., Ikuta, Koichi, Kaku, Mitsuo, Fujita, Jiro, and Kawakami, Kazuyoshi
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PNEUMOCOCCAL pneumonia , *CELLS , *LUNGS , *NEUTROPHILS - Abstract
Abstract: The present study was designed to elucidate the role of Vγ4+ γδ T cells, a major subset of pulmonary γδ T cells, in host defense against infection with Streptococcus pneumoniae. The proportion and number of whole γδ T cells, identified as CD3+ and TCR-δ+ cells, and Vγ4+ γδ T cells, identified as CD3+ and TCR-Vγ4+ cells, increased in the lungs at 3, 6 and 12h post-infection. Survival of infected mice and lung bacterial clearance were severely impaired in TCR-Vγ4−/− mice compared with control wild-type (WT) mice. The impaired host protection in TCR-Vγ4−/− mice correlated well with attenuated recruitment of neutrophils in lungs. MIP-2 and TNF-α synthesis in the infected tissues was significantly reduced in TCR-Vγ4−/− mice compared with WT mice. Similar results were noted in the synthesis of TNF-α, but not clearly of MIP-2, by lung leukocytes stimulated with live bacteria. Our results demonstrate that Vγ4+ γδ T cells play an important role in the neutrophil-mediated host defense against S. pneumoniae infection by promoting the synthesis of TNF-α and possibly of MIP-2 in the lungs. [Copyright &y& Elsevier]
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- 2007
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21. A new mechanism for generating TCR diversity: A TCR Jα-like gene that inserts partial nucleotide sequences in a D-gene manner
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Reardon, Christopher L., Hu, Ling-jia, Yin, Xiang, Born, Willi K., Arden, Bernhard, and O’Brien, Rebecca
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GENETICS , *GENES , *HEREDITY , *LYMPHOCYTES - Abstract
Abstract: δ-TCR genes of two γδ-T cell hybridomas were found to contain an identical 19-nt sequence in their non-germline N-regions. To determine if this sequence represented a third murine TCR Dδ gene, genomic PCR was performed by using it as a primer together with primers for interspersed repetitive elements (IRE). Sequencing revealed that the 19-nt segment is part of a 61-nt gene with flanking 5′ and 3′ recombination signaling sequences (RSS). Southern blot analysis confirmed the presence of this 61-nt gene in the genome of several mouse strains. The gene is unusual in that the distal 24 nucleotides of its 3′ RSS region are contributed by the 5′ portion of a B2 IRE sequence that includes an apparently non-functional RNA splice site within the 3′ nonamer sequence. It has sequence similarities with the Dδ1 gene (81%) at its 5′ end and with Jα genes (73%) overall. Tyramide-FISH analysis identified the gene to exist within or adjacent to the TCR α/δ locus on chromosome 14. Surveys of available TCR sequences reveal possible partial insertions of the 61-nt gene in other δ-TCR and in α-TCR gene sequences. Thus, the unique 61-nt gene is Jα gene-like in structure but D gene-like in function. [Copyright &y& Elsevier]
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- 2007
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22. Activation of Murine Epidermal Vγ5/Vδ1-TCR[sup +] T Cell Lines by Glu-Tyr Polypeptides.
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Seo, Seong Jun, Lahn, Michael, Cady, Carol, Vollmer, Michaelann, O'Brien, Rebecca L., Born, Willi K., and Reardon, Christopher L.
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T cell receptors , *ANTIGENS , *AMINO acids , *INTERLEUKIN-2 - Abstract
The physiologic role of gamma delta-T-cell-receptor-bearing cells and the T cell receptor ligands that they recognize is still poorly understood. Previous studies have suggested that one possible antigen for gamma delta-TCR[sup +] cells is the random copolymer poly-glutamic acid-tyrosine (poly-Glu-Tyr), because poly-Glu-Tyr-reactive gamma delta-TCR[sup +] hybridoma cells were produced from polyGlu-Tyr-immunized mice. We have found, however, that clonal Vgamma5/Vdelta1-TCR[sup +] epidermal T cell lines from nonimmune mice also respond to poly-GluTyr by producing cytokines. Other amino acid homopolymers, copolymers, and tripolymers were not stimulatory for the Vgamma5/Vdelta1-TCR[sup +] epidermal T cells, except for poly-glutamic acid-alanine-tyrosine (poly-Glu-Ala-Tyr). Of the poly-Glu-Tyr and polyGlu-Ala-Tyr polymers, only those that contained Glu and Tyr in an equimolar ratio were stimulatory. The cytokine interleukin-2 was strictly required for the responses to poly-Glu-Ala-Tyr, whereas the responses to poly-Glu-Tyr were merely enhanced with interleukin-2. The response to poly-Glu-Tyr was also enhanced by crosslinking CD28 molecules with plate-bound anti-CD28 crosslinking antibody. This finding suggests that the poly-Glu-Tyr response has a partial dependence on CD28-mediated costimulation, a characteristic of TCR-dependent responses. Consistent with this observation, Vgamma3/ Vdelta1-TCR-loss variants of the epidermal T cell line could no longer respond to poly-Glu-Tyr. The unpredicted responses of epidermal gamma delta-TCR[sup +] T cells to poly-Glu-Tyr and poly-Glu-Ala-Tyr demonstrate that the functions of these cells potentially can be triggered by peptidic ligands, probably through a TCR-mediated process. Key words: amino acids/IL-2/ mouse/ skin/ T lymphocytes. J Invest Dermatol 116:880885, 2001 [ABSTRACT FROM AUTHOR]
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- 2001
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23. Murine Epidermal Vγ5/Vδ1-T-Cell Receptor+ T Cells Respond to B-Cell Lines and Lipopolysaccharides.
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Reardon, Christopher L., Heyborne, Kent, Tsuji, Moriya, Zavala, Fidel, Tigelaar, Robert E., O'Brien, Rebecca L., and Born, Willi K.
- Subjects
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T cell receptors , *INTERLEUKIN-3 , *TUMOR necrosis factors , *LYMPHOCYTES , *CYTOKINES , *CELL receptors , *COLONY-stimulating factors (Physiology) - Abstract
The Vγ5/Vδ1+ -T-cell receptor (TCR)-bearing T-cell clone, 2CBET-3, was generated from C57BL/6 mice. Upon stimulation, 2CBET-3 cells produce interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-α, but not IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, macrophage colony-stimulating factor, or interferon-γ. These cells were evaluated for their ability to be stimulated by a variety of murine cell lines, including fibroblasts, trophoblasts, melanoma cells, embryonic carcinomas, B-cell lymphomas, mastocytoma cells, and keratinocytes. The human B-lymphoma cell and line, Daudi, also was included in these studies. We found that 2CBET-3 cells produced cytokines up to several hundredfold above the control levels in response to the B-cell line, Daudi, and A20/2J, but not to the B-cell line 439.4.2. After fixation with glutaraldehyde, Daudi and A20/2J continued to stimulate this γδ T-cell line. 2CBET-3 cells also responded to the keratinocyte line PAM212, but not to another, XB-2. When lipopolysaccharides (LPS) from Escherichia coli or S. typhimurium were added to 2CBET-3 calls in the presence of A20/2J cells, 2CBET-3 cells responded with increased cytokine production compared with the cytokine production in the presence of A20/2J cells alone. 2CBET-3 cells by themselves did not respond to LPS alone or to supernatants from A20/2J cells incubated with LPS. Unlike 2CBET-3, the epidermal T-cell hybridoma 70BET-49, expressing a Vγ5/Vδ1-TCR identical to that of 2CBET-3, did not respond to A20/2J cells in the presence or absence of LPS, suggesting a requirement for molecules other than the TCR for Vγ5/Vδ1-TCR+ T-cell stimulation by the B-cell lines and by LPS. This unique reactivity of γδ-TCR+ cells is defferent from that of γβ-TCR+ cells and may reflect a functional specialization of γδ-TCR+ cells in the response to bacterial infections. [ABSTRACT FROM AUTHOR]
- Published
- 1995
- Full Text
- View/download PDF
24. Response of a Murine Epidermal Vγ1/Vδ6-TCR+Hybridoma to Heat Shock Protein HSP-60.
- Author
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Reardon, Christopher L., Vollmer, Michaelann, Cranfill, Robin, van der Zee, Ruurd, O'Brien, Rebecca L., and Born, Willi K.
- Subjects
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T cells , *PEPTIDES , *EPIDERMIS , *CYTOKINES , *HYBRIDOMAS , *INTERLEUKIN-2 - Abstract
In the epidermis, the major population of T lymphocytes expresses a T-cell receptor (TCR) with VγS and Vδ1 variable regions, which is unique to this tissue. Roberts et al and Ezquerra et al, also describe a minor population of γδ-TCR+ cells in the epidermis that expresses a Vγ1/Vδ6 TCR. These cells are different from other epidermal T cells in that they "spontaneously" produce cytokines, a result thought to be due to auto-reactivity. Over the past 5 years, our laboratory has produced Vγ1/Vδ6+ T-cell hybridomas from many tissue sources. These spontaneously produce cytokines but also are activated by heat shock protein (HSP-60) -- derived peptides. Ezquerra et al report that none of their Vγ1/Vδ6+ epidermal T-cell lines derived from C3H/HeN mice respond to HSP-60. Of the 99 γδ- TCR+ hybridomas we have produced from epidermal T cells of C57BL/6 mice, only one expressed the Vγ1/ Vδ6 TCR. This hybridoma, 70BET-2.12, not only spontaneously produces cytokines, but, unlike the Vγ1 /Vδ6-TCR+ epidermal T cells of Ezquerra et al, it also responds to the whole HSP-60 protein and a 17- mer HSP-60 peptide from M. leprae, producing increased levels of interleukin-2 of up to approximately ten-fold above the spontaneous level. This shows that Vγ1/Vδ6-TCR+ epidermal T cells can respond to HSP-60. To confirm that 70BET-2.12 expresses TCR. genes similar to those of cells that have HSP-60 reactivity, Vγ1-Cγ4 and Vδ6-Cδ cDNA were produced from RNA isolated from this hybridoma, amplified by the polymerase chain reaction, and sequenced. The γ and δ TCR. gene sequences were similar but not identical to previously published sequences of HSP-60 -- reactive cells from lymphoid and other organs. No explanation can be found for the discrepancy between our findings and those of others at the level of TCR expression such that other strain-specific factors might be responsible for HSP-60 reactivity. [ABSTRACT FROM AUTHOR]
- Published
- 1994
- Full Text
- View/download PDF
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