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[PMID]: 25164823
[Au] Autor:Wakasugi M; Sasaki T; Matsumoto M; Nagaoka M; Inoue K; Inobe M; Horibata K; Tanaka K; Matsunaga T
[Ad] Address:From the Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan and....
[Ti] Title:Nucleotide Excision Repair-dependent DNA Double-strand Break Formation and ATM Signaling Activation in Mammalian Quiescent Cells.
[So] Source:J Biol Chem;289(41):28730-7, 2014 Oct 10.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Histone H2A variant H2AX is phosphorylated at Ser(139) in response to DNA double-strand break (DSB) and single-stranded DNA (ssDNA) formation. UV light dominantly induces pyrimidine photodimers, which are removed from the mammalian genome by nucleotide excision repair (NER). We previously reported that in quiescent G0 phase cells, UV induces ATR-mediated H2AX phosphorylation plausibly caused by persistent ssDNA gap intermediates during NER. In this study, we have found that DSB is also generated following UV irradiation in an NER-dependent manner and contributes to an earlier fraction of UV-induced H2AX phosphorylation. The NER-dependent DSB formation activates ATM kinase and triggers the accumulation of its downstream factors, MRE11, NBS1, and MDC1, at UV-damaged sites. Importantly, ATM-deficient cells exhibited enhanced UV sensitivity under quiescent conditions compared with asynchronously growing conditions. Finally, we show that the NER-dependent H2AX phosphorylation is also observed in murine peripheral T lymphocytes, typical nonproliferating quiescent cells in vivo. These results suggest that in vivo quiescent cells may suffer from NER-mediated secondary DNA damage including ssDNA and DSB.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.589747

  2 / 443703 MEDLINE  
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[PMID]: 25298684
[Au] Autor:Mostardeiro CP; Mostardeiro MA; Morel AF; Oliveira RM; Machado AK; Ledur P; Cadoná FC; da Silva UF; Mânica da Cruz IB
[Ad] Address:Department of Physiology, Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil....
[Ti] Title:The Pavonia xanthogloea (Ekman, Malvaceae): Phenolic compounds quantification, anti-oxidant and cytotoxic effect on human lymphocytes cells.
[So] Source:Pharmacogn Mag;10(Suppl 3):S630-8, 2014 Aug.
[Is] ISSN:0973-1296
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Pavonia xanthogloea is traditionally used as an antimicrobial and anti-tumour medicine in Southern Brazilian region. However, investigations about this species are still incipient. HYPOTHESIS TESTED: The study postulated that P. xanthologea specie present some phenolic compound and present some biological properties as anti-oxidant and cytoprotective effect against oxidative stress. MATERIALS AND METHODS: The content of eight phenolic molecules in the crude ethanolic extract of the aerial part of P. xanthogloea and its five fractions (hexane, dichloromethane, ethyl-acetate, n-butanol, and water) was determined by heterotrophic plate count method. The anti-oxidant capacity of the extract and the fractions was determined by 1,1-diphenyl-2-picryl-hydrazyl assay. The potential anti-oxidant and cytoprotective effect was also analyzed in human lymphocyte culture treated with extract/fractions at different concentrations with and without oxidative stress generated by hydrogen peroxide (H2O2) and sodium nitroprusside (SNP) exposition. RESULTS: Tiliroside was the molecule detected in all extract. Water and ethyl-acetate fractions showed the highest radical-scavenging activity. The crude extract, hexane, water, and n-butanol reversed the higher reactive oxygen specie levels generated by H2O2 and SNP to levels similar to those observed in the control group. In addition, crude extract, hexane, ethyl-acetate and n-butanol did not caused cytotoxicity, whereas water fraction was cytotoxic at higher concentration tested here (300 µg/mL). The cytotoxicity reversion caused by SNP exposition was concentration-dependent of the extract and fractions. However, dichloromethane fraction increased cell mortality in all concentrations investigated and was not able to decrease cell death in the lymphocytes exposed to SNP. CONCLUSION: The results suggest potential medicine use of this species.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Cu] Class update date: 141011
[Lr] Last revision date:141011
[Da] Date of entry for processing:141009
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.4103/0973-1296.139804

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[PMID]: 25296026
[Au] Autor:Lu Q; Wang JY; Wang L; Jiang X; Chu Y
[Ad] Address:Key Laboratory of Medical Molecular Virology of MOE/MOH, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China....
[Ti] Title:Self DNA from lymphocytes that have undergone activation-induced cell death enhances murine B cell proliferation and antibody production.
[So] Source:PLoS One;9(10):e109095, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Systemic lupus erythematosus (SLE) is characterized by prominent autoinflammatory tissue damage associated with impaired removal of dying cells and DNA. Self DNA-containing immune complexes are able to activate both innate and adaptive immune responses and play an important role in the maintenance and exacerbation of autoimmunity in SLE. In this study, we used DNA from lymphocytes that have undergone activation-induced cell death (ALD-DNA) and analyzed its role on the activation and differentiation of B cells from normal BALB/c mice as well as lupus-prone MRL+/+ and MRL/lpr mice. We found that ALD-DNA directly increased the expression of costimulatory molecules and the survival of naïve B cells in vitro. Although ALD-DNA alone had little effect on the proliferation of naïve B cells, it enhanced LPS-activated B cell proliferation in vitro and in vivo. In addition, ALD-DNA increased plasma cell numbers and IgG production in LPS-stimulated cultures of naïve B cells, in part via enhancing IL-6 production. Importantly, B cells from lupus mice were hyperresponsive to ALD-DNA and/or LPS relative to normal control B cells in terminal plasma cell differentiation, as evidenced by increases in CD138+ cell numbers, IgM production, and mRNA levels of B lymphocyte-induced maturation protein-1 (Blimp-1) and the X-box binding protein 1 (XBP1). Furthermore, ALD-DNA enhanced CD40-activated naïve B cell proliferation. Collectively, these data indicate that self DNA can serve as a DAMP (damage-associated molecular pattern) that cooperates with signals from both innate and adaptive immunity to promote polyclonal B cell activation, a common characteristic of autoimmune diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109095

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[PMID]: 25296025
[Au] Autor:Smith DJ; Hill GR; Bell SC; Reid DW
[Ad] Address:Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Queensland, Australia; School of Medicine, University of Queensland, Brisbane, Queensland, Australia; Infection and Inflammation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia....
[Ti] Title:Reduced Mucosal Associated Invariant T-Cells Are Associated with Increased Disease Severity and Pseudomonas aeruginosa Infection in Cystic Fibrosis.
[So] Source:PLoS One;9(10):e109891, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Primary defects in host immune responses have been hypothesised to contribute towards an inability of subjects with cystic fibrosis (CF) to effectively clear pulmonary infections. Innate T-lymphocytes provide rapid pathogen-specific responses prior to the development of classical MHC class I and II restricted T-cell responses and are essential to the initial control of pulmonary infection. We aimed to examine the relationship between peripheral blood lymphocyte phenotype and clinical outcomes in adults with CF. METHODS: We studied 41 subjects with CF and 22, age matched, non-smoking healthy control subjects. Lymphocytes were extracted from peripheral blood samples and phenotyped by flow-cytometry. Lymphocyte phenotype was correlated with sputum microbiology and clinical parameters. RESULTS: In comparison to healthy control subjects, mucosal associated invariant T (MAIT)-lymphocytes were significantly reduced in the peripheral blood of subjects with CF (1.1% versus 2.0% of T-lymphocytes, P = 0.002). MAIT cell concentration was lowest in CF subjects infected with P. aeruginosa and in subjects receiving treatment for a pulmonary exacerbation. Furthermore a reduced MAIT cell concentration correlated with severity of lung disease. CONCLUSION: Reduced numbers of MAIT cells in subjects with CF were associated with P. aeruginosa pulmonary infection, pulmonary exacerbations and more severe lung disease. These findings provide the impetus for future studies examining the utility of MAIT cells in immunotherapies and vaccine development. Longitudinal studies of MAIT cells as biomarkers of CF pulmonary infection are awaited.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109891

  5 / 443703 MEDLINE  
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[PMID]: 25295863
[Au] Autor:Chazal M; Nzounza P; Pique C; Ramirez BC
[Ad] Address:INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France....
[Ti] Title:Loss of Infectivity of HIV-1 Particles Produced by Mobile Lymphocytes.
[So] Source:PLoS One;9(10):e109601, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:HIV-1 spreads by cell-free particles and through direct cell contacts. To discriminate between these two modes of dissemination, an assay in which the cells are cultured under shaking conditions impairing cell-to-cell transmission has been described. We addressed the impact of shaking on HIV-1 particle infectivity. Kinetics of HIV-1 infection in static or shaking conditions confirmed that HIV-1 replication is reduced in mobile lymphocyte T cells. Strikingly, the infectivity of viruses produced by mobile lymphocytes was dramatically reduced. In parallel, the amount of envelope protein present on these particles showed a continuous decrease over time. We conclude that inefficient HIV-1 replication in mobile lymphocytes in this experimental system is not only due to avoidance of viral cell-to-cell transfer but also to the loss of infectivity of the viral particles due to the alteration of the composition and functionality of the particles produced by these lymphocytes. It is important to take these observations into account when studying viral transmission under shaking conditions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109601

  6 / 443703 MEDLINE  
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[PMID]: 25298957
[Au] Autor:Keyhani E; Sharghi SA; Amini R; Sharghi SA; Karimlou M; Moghaddam FA; Larijani B
[Ad] Address:Genetics Research Center-University of Social Welfare and Rehabilitation Sciences, Koudakyar st.-Daneshjoo blv., Tehran, (1985713834) Iran....
[Ti] Title:Liquid base cytology in evaluation of thyroid nodules.
[So] Source:J Diabetes Metab Disord;13(1):82, 2014.
[Is] ISSN:2251-6581
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Palpable thyroid nodules are present in 4-7% of general population and Fine Needle Aspiration (FNA) is now accepted by endocrinologists and thyroid surgeons as a safe, simple and cost effective procedure for evaluating a thyroid nodule. The obtained sample can be spread directly on slides, processed as cell block preparations or prepared as liquid base smears. Liquid base method has been recently accepted due to its shorter preparation time and better preservation of nuclear details. The aim of this study is to compare the diagnostic results of two commonly used methods: Liquid Base Preparation and Cell Block Preparation in evaluation of thyroid nodules. METHODS: The samples were taken from 100 patients with a solitary nodule or a prominent nodule on a multinodular goiter background (excluding hot nodules). The obtained samples were used to prepare conventional smears (CS), Cell Block Preparations (CBP) and Liquid Base Preparations (LBP). The slides were studied by two pathologists, considering the following parameters: Cellularity, Colloid, Lymphocytes/Plasma cells and Macrophages. RESULTS: 87% of cases revealed informative results in LBP method while in the same group of patients only 69% of samples were informative after processing by CBP method. Sensitivity and specificity of both methods compared with the conventional smears and with each other and it is concluded that LBP is a reliable method for evaluating of a thyroid nodule. Other studies also show the same results. CONCLUSION: The liquid base method should be trusted due to its easier procedure, cleaner slide background, its higher specificity and higher diagnostic yields. It can be used instead of CBP and in association with CS to increase the accuracy of evaluation of thyroid nodules.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Cu] Class update date: 141011
[Lr] Last revision date:141011
[Da] Date of entry for processing:141009
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1186/s40200-014-0082-5

  7 / 443703 MEDLINE  
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[PMID]: 25291178
[Au] Autor:Cai X; Dai Z; Reeves RS; Caballero-Benitez A; Duran KL; Delrow JJ; Porter PL; Spies T; Groh V
[Ad] Address:Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America....
[Ti] Title:Autonomous Stimulation of Cancer Cell Plasticity by the Human NKG2D Lymphocyte Receptor Coexpressed with Its Ligands on Cancer Cells.
[So] Source:PLoS One;9(10):e108942, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The stimulatory NKG2D receptor on lymphocytes promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells. Progressing tumors counteract by employing tactics to disable lymphocyte NKG2D. This negative dynamic is escalated as some human cancer cells co-opt expression of NKG2D, thereby complementing the presence of its ligands for autonomous stimulation of oncogenic signaling. Clinical association data imply relationships between cancer cell NKG2D and metastatic disease. Here we show that NKG2D promotes cancer cell plasticity by induction of phenotypic, molecular, and functional signatures diagnostic of the epithelial-mesenchymal transition, and of stem-like traits via induction of Sox9, a key transcriptional regulator of breast stem cell maintenance. These findings obtained with model breast tumor lines and xenotransplants were recapitulated by ex vivo cancer cells from primary invasive breast carcinomas. Thus, NKG2D may have the capacity to drive high malignancy traits underlying metastatic disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0108942

  8 / 443703 MEDLINE  
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[PMID]: 25289687
[Au] Autor:Dörrie J; Krug C; Hofmann C; Müller I; Wellner V; Knippertz I; Schierer S; Thomas S; Zipperer E; Printz D; Fritsch G; Schuler G; Schaft N; Geyeregger R
[Ad] Address:Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany....
[Ti] Title:Human Adenovirus-Specific γ/δ and CD8+ T Cells Generated by T-Cell Receptor Transfection to Treat Adenovirus Infection after Allogeneic Stem Cell Transplantation.
[So] Source:PLoS One;9(10):e109944, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Human adenovirus infection is life threatening after allogeneic haematopoietic stem cell transplantation (HSCT). Immunotherapy with donor-derived adenovirus-specific T cells is promising; however, 20% of all donors lack adenovirus-specific T cells. To overcome this, we transfected α/ß T cells with mRNA encoding a T-cell receptor (TCR) specific for the HLA-A*0101-restricted peptide LTDLGQNLLY from the adenovirus hexon protein. Furthermore, since allo-reactive endogenous TCR of donor T lymphocytes would induce graft-versus-host disease (GvHD) in a mismatched patient, we transferred the TCR into γ/δ T cells, which are not allo-reactive. TCR-transfected γ/δ T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8α-encoding mRNA. In direct comparison with TCR-transfected α/ß T cells, TCR-CD8α-co-transfected γ/δ T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected α/ß T cells and TCR-CD8α-co-transfected γ/δ T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only α/ß T cells but also γ/δ T cells can be equipped with an adenovirus specificity by TCR-RNA electroporation. Thus, our strategy offers a new means for the immunotherapy of adenovirus infection after allogeneic HSCT.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109944

  9 / 443703 MEDLINE  
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[PMID]: 25277150
[Au] Autor:Siva S; Callahan J; Kron T; Martin OA; MacManus MP; Ball DL; Hicks RJ; Hofman MS
[Ad] Address:Division of Radiation Oncology and Cancer Imaging, St Andrews Place, East Melbourne 3002, Australia. shankar.siva@petermac.org.
[Ti] Title:A prospective observational study of Gallium-68 ventilation and perfusion PET/CT during and after radiotherapy in patients with non-small cell lung cancer.
[So] Source:BMC Cancer;14:740, 2014.
[Is] ISSN:1471-2407
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer deaths. Radiation therapy (RT), alone or in combination with chemotherapy, is the standard of care for curative intent treatment of patients with locally advanced or inoperable NSCLC. The ability to intensify treatment to achieve a better chance for cure is limited by the risk of injury to the surrounding lung. METHODS/DESIGN: This is a prospective observational study of 60 patients with NSCLC receiving curative intent RT. Independent human ethics board approval was received from the Peter MacCallum Cancer Centre ethics committee. In this research, Galligas and Gallium-68 macroaggregated albumin (MAA) positron emission tomography (PET) imaging will be used to measure ventilation (V) and perfusion (Q) in the lungs. This is combined with computed tomography (CT) and both performed with a four dimensional (4D) technique that tracks respiratory motion. This state-of-the-art scan has superior resolution, accuracy and quantitative ability than previous techniques. The primary objective of this research is to observe changes in ventilation and perfusion secondary to RT as measured by 4D V/Q PET/CT. Additionally, we plan to model personalised RT plans based on an individual's lung capacity. Increasing radiation delivery through areas of poorly functioning lung may enable delivery of larger, more effective doses to tumours without increasing toxicity. By performing a second 4D V/Q PET/CT scan during treatment, we plan to simulate biologically adapted RT depending on the individual's accumulated radiation injury. Tertiary aims of the study are assess the prognostic significance of a novel combination of clinical, imaging and serum biomarkers in predicting for the risk of lung toxicity. These biomarkers include spirometry, 18 F-Fluorodeoxyglucose PET/CT, gamma-H2AX signals in hair and lymphocytes, as well as assessment of blood cytokines. DISCUSSION: By correlating these biomarkers to toxicity outcomes, we aim to identify those patients early who will not tolerate RT intensification during treatment. This research is an essential step leading towards the design of future biologically adapted radiotherapy strategies to mitigate the risk of lung injury during dose escalation for patients with locally advanced lung cancer. TRIALS REGISTRATION: Universal Trial Number (UTN) U1111-1138-4421.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/1471-2407-14-740

  10 / 443703 MEDLINE  
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[PMID]: 25220211
[Au] Autor:Van Kaer L; Algood HM; Singh K; Parekh VV; Greer MJ; Piazuelo MB; Weitkamp JH; Matta P; Chaturvedi R; Wilson KT; Olivares-Villagómez D
[Ad] Address:Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: luc.van.kaer@vanderbilt.edu....
[Ti] Title:CD8αα(+) Innate-Type Lymphocytes in the Intestinal Epithelium Mediate Mucosal Immunity.
[So] Source:Immunity;41(3):451-64, 2014 Sep 18.
[Is] ISSN:1097-4180
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8α cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting that these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8α cells in immune responses associated with the intestinal epithelium.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review


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