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[PMID]: 25143585
[Au] Autor:Farr AR; Wu W; Choi B; Cavalcoli JD; Laouar Y
[Ad] Address:Departments of Microbiology and Immunology and....
[Ti] Title:CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells.
[So] Source:Proc Natl Acad Sci U S A;111(35):12841-6, 2014 Sep 2.
[Is] ISSN:1091-6490
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Invariant natural killer T (iNKT) cells to date represent the best example of cells known to have a hybrid function, representing both innate and adaptive immunity. Shared phenotypic similarities with NK cells together with a rapid response to a cytokine stimulus and a productive TCR engagement are the features that underline the hybrid nature of iNKT cells. Using these criteria, we provide molecular and functional evidence demonstrating that CD1d-independent (CD1d(ind)) NKT cells, a population of CD1d-unrestricted NKT cells, are endowed with a hybrid function far superior to that of iNKT cells: (i) an extensive shared program with NK cells, (ii) a closer Euclidian distance with NK cells, and (iii) the ability to respond to innate stimuli (Poly:IC) with cytotoxic potential in the same manner as NK cells identify a hybrid feature in CD1d(ind)NKT cells that truly fulfills the dual function of an NK and a T cell. Our finding that CD1d(ind)NKT cells are programmed to act like NK cells in response to innate signals while being capable of adaptive responses is unprecedented, and thus might reemphasize CD1d-unrestricted NKT cells as a subset of lymphocytes that could affect biological processes of antimicrobial and tumor immunity in a unique way.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1073/pnas.1323405111

  2 / 442323 MEDLINE  
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[PMID]: 25197429
[Au] Autor:Borska L; Andrys C; Krejsek J; Palicka V; Chmelarova M; Hamakova K; Kremlacek J; Fiala Z
[Ad] Address:Institute of Pathological Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 50038 Hradec Kralove, Czech Republic....
[Ti] Title:Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation.
[So] Source:Oxid Med Cell Longev;2014:302528, 2014.
[Is] ISSN:1942-0994
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1155/2014/302528

  3 / 442323 MEDLINE  
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[PMID]: 25186961
[Au] Autor:Fisher SA; Cleaver A; Lakhiani DD; Khong A; Connor T; Wylie B; Lesterhuis WJ; Robinson BW; Lake RA
[Ad] Address:School of Medicine & Pharmacology, University of Western Australia, Perth, 4th Floor, G Block, Queen Elizabeth II Medical Centre, Perth 6009, WA, Australia. scott.fisher@uwa.edu.au.
[Ti] Title:Neoadjuvant anti-tumor vaccination prior to surgery enhances survival.
[So] Source:J Transl Med;12(1):245, 2014.
[Is] ISSN:1479-5876
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: This study was conducted to determine if anti-tumor vaccination administered prior to partial debulking surgery could improve survival using a murine solid tumour model. METHODS: Tumor incidence and survival rates were compared in mice bearing subcutaneous AB1-HA mesothelioma tumors that received either sham surgery, debulking surgery or vaccination prior to debulking surgery. Additionally, mice were depleted of CD4 and/or CD8 T lymphocytes during vaccination to assess their involvement in vaccine induced anti-tumor immunity. Flow cytometry was performed to characterise changes in the proportion and activation status of immune cells associated with anti-tumor immunity. RESULTS: Neoadjuvant vaccination combined with debulking surgery resulted in decreased tumor burden, increased survival and generation of tumor-specific immunity compared to surgery alone. Depletion of CD8 T cells completely abrogated any vaccine induced anti-tumor immune response. Conversely, CD4 depletion enhanced CD8 T cell activation resulting in complete tumor regression in 70% of mice treated with combined surgery and vaccination therapy. Tumor free survival was associated with established immunological memory as defined by the induction of effector memory T cells and resistance to rechallenge with parental AB1 mesothelioma cells. CONCLUSIONS: Neoadjuvant anti-cancer vaccination combined with partial debulking surgery induced CD8-dependent anti-tumor immunity that significantly delayed tumor outgrowth relative to surgery alone. Complete tumor eradication was observed when vaccination and surgery were performed in CD4 T cell depleted animals. This demonstrates that adjuvant immunotherapy can improve post-surgical survival following cancer debulking surgery and provides a scientific rational for clinical trials of such an approach.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s12967-014-0245-7

  4 / 442323 MEDLINE  
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[PMID]: 25106834
[Au] Autor:Tokgoz S; Keskin S; Kayrak M; Seyithanoglu A; Ogmegul A
[Ad] Address:Department of Neurology, Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey....
[Ti] Title:Is Neutrophil/Lymphocyte Ratio Predict to Short-term Mortality in Acute Cerebral Infarct Independently from Infarct Volume?
[So] Source:J Stroke Cerebrovasc Dis;23(8):2163-8, 2014 Sep.
[Is] ISSN:1532-8511
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Neutrophil/lymphocyte ratio (NLR) is related with increased mortality in both myocardial infarction and acute ischemic stroke. It remains unclear whether NLR is a simple marker of ischemic infarct volume or an independent marker of stroke mortality. The aim of this study is to investigate the relationship of NLR with infarct volume and short-term mortality in acute ischemic stroke (AIS). METHODS: This retrospective study included 151 patients with first AIS that occurred within 24hours of symptom onset. Patients were screened from the hospital's electronic record system by using International Classification of Diseases code (G 46.8). NLR was calculated as the ratio of neutrophils to lymphocytes. Short-term mortality was defined as 30-day mortality. RESULTS: A total 20 of 151 patients died during follow-up. Both NLR and infarct volume of nonsurvived group were significantly higher than survived group (P<.05). Infarct volume, NLR, and National Institutes of Health Stroke Scale (NIHSS) were independent predictors of the mortality in Cox regression analysis. The optimal cutoff value for NLR as a predictor for short-term mortality was determined as 4.81. NLR displayed a moderate correlation with both NIHSS and Glasgow Coma Scale (P<.01). NLR values were significantly higher in the highest infarct volume tertile than both in the lowest volume tertile and midtertile of infarct volume (P=.001). CONCLUSIONS: NLR at the time of hospital admission maybe a predictor of short-term mortality independent from infarct volume in AIS patients. NLR should be investigated in future prospective trials investigating AIS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  5 / 442323 MEDLINE  
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[PMID]: 25197555
[Au] Autor:Beard RE; Zheng Z; Lagisetty KH; Burns WR; Tran E; Hewitt SM; Abate-Daga D; Rosati SF; Fine HA; Ferrone S; Rosenberg SA; Morgan RA
[Ad] Address:Surgery Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Building 10 Hatfield CRC, Rm 3-5930, 20892-1201 Bethesda, MD, USA....
[Ti] Title:Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells.
[So] Source:J Immunother Cancer;2:25, 2014.
[Is] ISSN:2051-1426
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The development of immunotherapy has led to significant progress in the treatment of metastatic cancer, including the development of genetic engineering technologies that redirect lymphocytes to recognize and target a wide variety of tumor antigens. Chimeric antigen receptors (CARs) are hybrid proteins combining antibody recognition domains linked to T cell signaling elements. Clinical trials of CAR-transduced peripheral blood lymphocytes (PBL) have induced remission of both solid organ and hematologic malignancies. Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target antigen that is overexpressed in multiple cancer histologies including melanoma, triple-negative breast cancer, glioblastoma, mesothelioma and sarcoma. METHODS: CSPG4 expression in cancer cell lines was assayed using flow cytometry (FACS) and reverse-transcription PCR (RT-PCR). Immunohistochemistry was utilized to assay resected melanomas and normal human tissues (n = 30) for CSPG4 expression and a reverse-phase protein array comprising 94 normal tissue samples was also interrogated for CSPG4 expression. CARs were successfully constructed from multiple murine antibodies (225.28S, TP41.2, 149.53) using second generation (CD28.CD3ζ) signaling domains. CAR sequences were cloned into a gamma-retroviral vector with subsequent successful production of retroviral supernatant and PBL transduction. CAR efficacy was assayed by cytokine release and cytolysis following coculture with target cell lines. Additionally, glioblastoma stem cells were generated from resected human tumors, and CSPG4 expression was determined by RT-PCR and FACS. RESULTS: Immunohistochemistry demonstrated prominent CSPG4 expression in melanoma tumors, but failed to demonstrate expression in any of the 30 normal human tissues studied. Two of 94 normal tissue protein lysates were positive by protein array. CAR constructs demonstrated cytokine secretion and cytolytic function after co-culture with tumor cell lines from multiple different histologies, including melanoma, breast cancer, mesothelioma, glioblastoma and osteosarcoma. Furthermore, we report for the first time that CSPG4 is expressed on glioblastoma cancer stem cells (GSC) and demonstrate that anti-CSPG4 CAR-transduced T cells recognize and kill these GSC. CONCLUSIONS: The functionality of multiple different CARs, with the widespread expression of CSPG4 on multiple malignancies, suggests that CSPG4 may be an attractive candidate tumor antigen for CAR-based immunotherapies using appropriate technology to limit possible off-tumor toxicity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Da] Date of entry for processing:140908
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1186/2051-1426-2-25

  6 / 442323 MEDLINE  
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[PMID]: 25194410
[Au] Autor:Nayer A; Green DF; Gonzalez-Suarez ML; Sujoy V; Ikpatt OF; Thomas DB
[Ad] Address:Division of Nephrology and Hypertension, University of Miami, Miami, FL, USA. anayer@med.miami.edu.
[Ti] Title:Tubulointerstitial nephritis accompanying gamma-heavy chain deposition and gamma-heavy chain restricted plasma cells in the kidney.
[So] Source:Iran J Kidney Dis;8(5):417-23, 2014 Sep.
[Is] ISSN:1735-8604
[Cp] Country of publication:Iran
[La] Language:eng
[Ab] Abstract:Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, -, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  7 / 442323 MEDLINE  
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[PMID]: 25197420
[Au] Autor:Li D; Huang L; Guo B; Wen Q; Wang W; Luo J; Fan S
[Ad] Address:Department of Pathology, the Second Xiangya Hospital, Central South University Changsha, Hunan, China....
[Ti] Title:Primary cutaneous γδ-T-cell lymphoma (CGD-TCL) with unilateral lower extremity swelling as first-onset symptom: a rare case report.
[So] Source:Int J Clin Exp Pathol;7(8):5337-42, 2014.
[Is] ISSN:1936-2625
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Primary cutaneous γδ-T-cell lymphoma (CGD-TCL) is a distinct disease entity which is an extremely rare neoplasm with poor prognosis, characterized by the γ/δ T-cell receptor expression on atypical lymphocytes. We report the case of a 42-year-old man who first presented with a swelling in the extremities and subsequent appeared subcutaneous nodule over the body. In order to clarify the diagnosis, a biopsy of subcutaneous nodule for pathology had been done. CGD-TCL was diagnosed by histopathology, immunophenotype, in situ hybridization and analysis of TCRγ genes rearrangement. The patient was treated with chemotherapeutic regimens-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone). After one period of chemotherapy, subcutaneous nodules became small, even disappeared, swelling and ulcer in the left pedal gone away gradually. One month later after first chemotherapy, tumor relapsed with lesions growing back rapidly, also showed disease in double lungs. The patient was just 10-month survival time from the onset. To our knowledge, this case is the first report of CGD-TCL with unilateral lower extremity swelling as the first-onset symptom. If patient is presented the first symptoms such as swelling of extremities, especially when ulceration appears, it is of great significance to be considerate about the possibility of CGD-TCL.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  8 / 442323 MEDLINE  
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[PMID]: 25197369
[Au] Autor:Chu H; Liu X; Zhao J; Xu Y; Wang L; Wang T; Guo W; Zhang S; Zhu X
[Ad] Address:Center of General Surgery, The 89th Hospital of People's Liberation Army Weifang, China....
[Ti] Title:Subtotal splenectomy for splenomegaly in cirrhotic patients.
[So] Source:Int J Clin Exp Pathol;7(8):4981-90, 2014.
[Is] ISSN:1936-2625
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: In recent years, the spleen has become to be recognized as the "control center" of the immune-metabolic-endocrine network. However, It is controversial that splenomegaly due to portal hypertension is treated by subtotal splenectomy. The aim of this study was to evaluate the distribution of fibrous tissue, morphology of cells as well as splenic size, hemodynamics, hematological and immunological indexes in the residual spleen after subtotal splenectomy. This information may help finding the basis for the operation of subtotal splenectomy. METHODS: Ten cases of splenomegaly due to portal hypertension were investigated. Two groups were created: Splenomegaly and Residual spleen. Control group was 10 cases of trauma-induced splenic rupture. Samples were sliced, and morphological changes were observed under light microscopy and electron microscopy. Indexes of splenic size, hemodynamics, hematology and immunology of the spleen were measured. RESULTS: Under light microscopy, the number of collagen fibers and elastic fibers was increased, and the number of reticular fibers was decreased in the residual spleen and splenomegaly groups. Under electron microscopy, the ultrastructure of endothelial cells, lymphocytes, macrophages, and reticular cells in the residual spleen group were noticeably improved more than in the splenomegaly group. Flow volume in the residual spleen and portal vein decreased obviously, with number of platelet rising to normal, and there was no significant difference in the indexes of immunology. CONCLUSION: After subtotal splenectomy, the residual spleen will not experience a high-pressure environment, and the fibrosis of splenic tissue and remodelling of corpuscular morphology will cease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  9 / 442323 MEDLINE  
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[PMID]: 25197359
[Au] Autor:Li X; Xu B; Wang Y; Wei L
[Ad] Address:Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital Hefei, Anhui Province, P.R. China....
[Ti] Title:Anti-inflammatory effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) on non-obese diabetic mice with Sjogren's syndrome.
[So] Source:Int J Clin Exp Pathol;7(8):4886-94, 2014.
[Is] ISSN:1936-2625
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To investigate the anti-inflammatory effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) on non-obese diabetic mice (NOD mice) with Sjogren's syndrome. METHODS: 22 eight-week-old female NOD mice were randomly divided into 2 groups. Rosiglitazone and normal saline were administered in the PPAR-γ group and the control group respectively. At the age of 9, 12 and 15 weeks, one mouse in each group was sacrificed respectively, and the remaining mice were sacrificed at the age of 18 weeks. Blood were obtained by cardiac puncture, and salivary glands were resected. The degree of salivary gland damage and infiltration of lymphocytes were examined by H&E staining. The level of IL-1, IL-4, IL-6 and TNF-α in serum were measured by ELISA. The mRNA expression level of IL-1, IL-4, IL-6 and TNF-α in MSG were detected by Real-time PCR. Expression of PPAR-γ in the salivary glands was detected by Immunohistochemistry. RESULTS: Compared with the control group, mice in the PPAR-γ group showed that (1) histopathologic changes in the salivary glands were significantly ameliorated; (2) at the age of 18 weeks, IL-6 [(25.86 7.32) vs (37.41 11.34)] and TNF-α [(56.88 22.19) vs (78.61 20.76)] were expressed significantly lower and IL-4 [(25.76 12.65) vs (12.11 3.70)] was expressed significantly higher in serum (P < 0.05); (3) the expression of TNF-α was significantly decreased and the expression of IL-4 was significantly increased in MSG (P < 0.05). CONCLUSION: PPAR-γ ameliorates Sjogren's syndrome on NOD mice effectively. The mechanism may be related to the reduction of Th1 cytokines and change of T helper cell balance from Th1 to Th2.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 442323 MEDLINE  
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[PMID]: 24689455
[Au] Autor:Thom R; Issayama LK; Alves da Costa T; Gangi RD; Ferreira IT; Rapso C; Lopes SC; da Cruz Hfling MA; Costa FT; Verinaud L
[Ad] Address:Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, So Paulo, Brazil.
[Ti] Title:Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation.
[So] Source:Immunology;143(2):164-73, 2014 Oct.
[Is] ISSN:1365-2567
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P.berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P.berghei extracts are able to control autoimmune neuroinflammation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/imm.12298


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