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[PMID]: 24419333
[Au] Autor:Clarke AJ; Ellinghaus U; Cortini A; Stranks A; Simon AK; Botto M; Vyse TJ
[Ad] Address:Medical and Molecular Genetics and Division of Immunology, Infection, and Inflammatory Disease, King's College London, London, UK....
[Ti] Title:Autophagy is activated in systemic lupus erythematosus and required for plasmablast development.
[So] Source:Ann Rheum Dis;74(5):912-20, 2015 May.
[Is] ISSN:1468-2060
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Autophagy has emerged as a critical homeostatic mechanism in T lymphocytes, influencing proliferation and differentiation. Autophagy in B cells has been less studied, but genetic deficiency causes impairment of early and late developmental stages OBJECTIVES: To explore the role of autophagy in the pathogenesis of human and murine lupus, a disease in which B cells are critical effectors of pathology. METHODS: Autophagy was assessed using multiple techniques in NZB/W and control mice, and in patients with systemic lupus erythematosus (SLE) compared to healthy controls. We evaluated the phenotype of the B cell compartment in Vav-Atg7(-/-) mice in vivo, and examined human and murine plasmablast formation following inhibition of autophagy. RESULTS: We found activation of autophagy in early developmental and transitional stages of B cell development in a lupus mouse model even before disease onset, and which progressively increased with age. In human disease, again autophagy was activated compared with healthy controls, principally in naïve B cells. B cells isolated from Vav-Atg7(F/F) mice failed to effectively differentiate into plasma cells following stimulation in vitro. Similarly, human B cells stimulated in the presence of autophagy inhibition did not differentiate into plasmablasts. CONCLUSIONS: Our data suggest activation of autophagy is a mechanism for survival of autoreactive B cells, and also demonstrate that it is required for plasmablast differentiation, processes that induce significant cellular stress. The implication of autophagy in two major pathogenic pathways in SLE suggests the potential to use inhibition of autophagy as a novel treatment target in this frequently severe autoimmune disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/annrheumdis-2013-204343

  2 / 449974 MEDLINE  
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[PMID]: 25640181
[Au] Autor:Lui JB; Devarajan P; Teplicki SA; Chen Z
[Ad] Address:Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA....
[Ti] Title:Cross-differentiation from the CD8 lineage to CD4 T cells in the gut-associated microenvironment with a nonessential role of microbiota.
[So] Source:Cell Rep;10(4):574-85, 2015 Feb 3.
[Is] ISSN:2211-1247
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:CD4 and CD8 T cell lineages differentiate through respective thymic selection processes. Here, we report cross-differentiation from the CD8 lineage to CD4 T cells, but not vice versa, predominantly in the large-intestine-associated microenvironment. It occurred in the absence or distal presence of cognate antigens. This pathway produced MHC-class-I-restricted CD4(+)Foxp3(+) T(reg) (CI-T(reg)) cells. Blocking T cell-intrinsic TGFß signaling diminished CI-Treg populations in lamina propria, but it did not preclude the CD8-to-CD4 conversion. Microbiota were not required for the cross-differentiation, but the presence of microbiota led to expansion of the converted CD4 T cell population in the large intestine. CI-T(reg) cells did not promote tolerance to microbiota per se, but they regulated systemic homeostasis of T lymphocytes and protected the large intestine from inflammatory damage. Overall, the clonal conversion from the CD8 lineage to CD4 T cell subsets occurred regardless of "self" or "nonself." This lineage plasticity may promote "selfless" tolerance for immune balance.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Process

  3 / 449974 MEDLINE  
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[PMID]: 25424159
[Au] Autor:Yalcinkaya E; Yuksel UC; Celik M; Kabul HK; Barcin C; Gokoglan Y; Yildirim E; Iyisoy A
[Ad] Address:Department of Cardiology, Aksaz Military Hospital....
[Ti] Title:Relationship between Neutrophil-To-Lymphocyte Ratio and Electrocardiographic Ischemia Grade in STEMI.
[So] Source:Arq Bras Cardiol;104(2):112-9, 2015 Feb.
[Is] ISSN:1678-4170
[Cp] Country of publication:Brazil
[La] Language:eng; por
[Ab] Abstract:BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Changes in the QRS terminal portion have also been associated with adverse outcomes following STEMI. OBJECTIVE: To investigate the relationship between ECG ischemia grade and NLR in patients presenting with STEMI, in order to determine additional conventional risk factors for early risk stratification. METHODS: Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG performed on admission. White blood cells and subtypes were measured as part of the automated complete blood count (CBC) analysis. Patients were classified into two groups according to the ischemia grade presented on the admission ECG, as grade 2 ischemia (G2I) and grade 3 ischemia (G3I). RESULTS: Patients with G3I had significantly lower mean left ventricular ejection fraction than those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital mortality rate increased proportionally with the increase in ischemia grade (p = 0.036). There were significant differences in percentage of lymphocytes (p = 0.010) and percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis revealed that only NLR was the independent variable with a significant effect on ECG ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120-1.403, p < 0.001). CONCLUSION: We found an association between G3I and elevated NLR in patients with STEMI. We believe that such an association might provide an additional prognostic value for risk stratification in patients with STEMI when combined with standardized risk scores.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 449974 MEDLINE  
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[PMID]: 25834361
[Au] Autor:Jeon J; Kim JH; Ahn JW; Song HJ
[Ad] Address:Department of Dermatology, Korea University Guro Hospital, Seoul, Korea....
[Ti] Title:Poikiloderma vasculare atrophicans showing features of ashy dermatosis in the beginning.
[So] Source:Ann Dermatol;27(2):197-200, 2015 Apr.
[Is] ISSN:1013-9087
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:Poikiloderma vasculare atrophicans (PVA) is a rare poikilodermatous variant of early-stage mycosis fungoides characterized by generalized poikiloderma, atrophy, mottled dyspigmentation, and telangiectasia. In 2001, a 14-year-old male presented with asymptomatic brownish-gray polymorphic macules throughout the body with flexural accentuation. A skin biopsy showed increased melanophages with focal hydropic changes. Ashy dermatosis was considered a possible diagnosis. In 2005, the lesions began to show darkening and lichenification in the lower part of the trunk. In 2011, his skin showed definite poikilodermatous changes, and a biopsy showed band-like inflammatory infiltrations of atypical lymphocytes, epidermal atrophy, and epidermotropism of predominantly CD4(-)CD8(+) atypical T cells. In addition, results of T-cell receptor gene rearrangement analysis were positive. Based on the aforementioned findings, he was diagnosed with PVA. If a patient shows long-standing and progressive hyperpigmentary skin changes, periodic follow-up and repeated skin biopsies are recommended to determine the underlying condition.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Da] Date of entry for processing:150402
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.5021/ad.2015.27.2.197

  5 / 449974 MEDLINE  
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[PMID]: 25827591
[Au] Autor:Senthilkumaran C; Hewson J; Ollivett TL; Bienzle D; Lillie BN; Clark M; Caswell JL
[Ti] Title:Localization of annexins A1 and A2 in the respiratory tract of healthy calves and those experimentally infected with Mannheimia haemolytica.
[So] Source:Vet Res;46(1):6, 2015.
[Is] ISSN:1297-9716
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Annexins A1 and A2 are proteins known to function in the stress response, dampening inflammatory responses and mediating fibrinolysis. We found, in healthy cattle recently arrived to a feedlot, that lower levels of these proteins correlated with later development of pneumonia. Here we determine the localization of annexin A1 and A2 proteins in the respiratory tract and in leukocytes, in healthy calves and those with Mannheimia haemolytica pneumonia. In healthy calves, immunohistochemistry revealed cytoplasmic expression of annexin A1 in the surface epithelium of large airways, tracheobronchial glands and goblet cells, to a lesser degree in small airways, but not in alveolar epithelium. Immunocytochemistry labeled annexin A1 in the cytoplasm of neutrophils from blood and bronchoalveolar lavage fluid, while minimal surface expression was detected by flow cytometry in monocytes, macrophages and lymphocytes. Annexin A2 expression was detected in surface epithelium of small airways, some mucosal lymphocytes, and endothelium, with weak expression in large airways, tracheobronchial glands and alveolar septa. For both proteins, the level of expression was similar in tissues collected five days after intrabronchial challenge with M. haemolytica compared to that from sham-inoculated calves. Annexins A1 and A2 were both detected in leukocytes around foci of coagulative necrosis, and in necrotic cells in the center of these foci, as well as in areas outlined above. Thus, annexins A1 and A2 are proteins produced by airway epithelial cells that may prevent inflammation in the healthy lung and be relevant to development of pneumonia in stressed cattle.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s13567-014-0134-3

  6 / 449974 MEDLINE  
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[PMID]: 25825555
[Au] Autor:Agarwal MB; Jijina F; Shah S; Malhotra P; Damodar S; Ross C
[Ad] Address:Hematology Centre, Ghamat Lodge, 2nd Floor, Above ING Vaishya Bank, 804 A, Dr. B. Ambedkar Road, Dadar TT, Mumbai, India....
[Ti] Title:Safety and efficacy of indigenous equine antithymocyte globulin along with cyclosporine in subjects with acquired aplastic anemia.
[So] Source:Indian J Hematol Blood Transfus;31(2):174-9, 2015 Jun.
[Is] ISSN:0971-4502
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:To confirm the safety and efficacy of an indigenous equine antithymocyte globulin (eATG) along with cyclosporine in Indian subjects with acquired aplastic anaemia. Subjects >2 years old with acquired aplastic anaemia were enrolled at six hospitals between April 2011 and February 2013, after approval from respective Ethics Committees. Equine ATG at a dose of 40 mg/kg/day was infused for 4 days. Efficacy analysis defined a priori, was in subjects, who had completed eATG treatment and followed-up on day 90 and/or 180. Complete response (CR) was defined as-transfusion independent, haemoglobin ≥11 g/dL, absolute neutrophil count (ANC) >1.5 10(9)/L and platelet ≥150 10(9)/L; partial response (PR) was transfusion independent, haemoglobin ≥8 g/dL, ANC >0.5 10(9)/L and platelet ≥20 10(9)/L; non responders were transfusion dependent. Lymphocyte subsets (CD 2, 3, 4 and 8) in the blood were tested on days 0 (pre eATG infusion), 3, 5, 7, 14 and 21 after eATG. Of the 30 subjects (two children <12 years old) enrolled, 19 completed day 90 and 18 completed day 180 visit. Of the remaining 11 subjects, two died on days 12 and 45 due to septicaemia and pneumonia, one was withdrawn after the first dose of eATG due to jaundice and eight were lost to follow-up. The median age was 30 (9-58) years and weight was 57 (26-84) kg. On day 90, 12 of 30 subjects responded (CR 1, PR 11) and 15 of 30 (CR 2, PR 13) on day 180. The most common adverse event was fever related to eATG infusion. There were two serious adverse events (acute renal failure, febrile neutropenia) and both recovered with treatment. There were no unusual adverse events noted during the study period. Blood T lymphocytes showed a mean decrease of 91 % from baseline that recovered by day 21. We conclude that eATG is safe and in combination with cyclosporine showed overall response in 50 % of enrolled subjects. The trial was registered with the clinical trial registry-india (Registration no. CTRI/2012/03/002498).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Da] Date of entry for processing:150331
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1007/s12288-014-0423-z

  7 / 449974 MEDLINE  
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[PMID]: 25257108
[Au] Autor:Clark SM; Michael KC; Klaus J; Mert A; Romano-Verthelyi A; Sand J; Tonelli LH
[Ad] Address:Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States....
[Ti] Title:Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-/-) mice.
[So] Source:Behav Brain Res;278:74-82, 2015 Feb 1.
[Is] ISSN:1872-7549
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Inflammatory diseases are highly associated with affective disorders including depression and anxiety. While the role of the innate immune system on emotionality has been extensively studied, the role of adaptive immunity is less understood. Considering that chronic inflammatory conditions are mediated largely by maladaptive lymphocyte function, the role of these cells on brain function and behavior during inflammation warrants investigation. In the present study we employed mice deficient in lymphocyte function and studied behavioral and inflammatory responses during challenge with bacterial lipopolysaccharides (LPS). Rag2(-/-) mice lacking mature lymphocytes were susceptible to death under sub-septic (5mg/kg) doses of LPS and survived only to moderate (1mg/kg) doses of LPS. Under these conditions, they displayed attenuated TNF-alpha responses and behavioral symptoms of sickness when compared with immunocompetent mice. Nevertheless, Rag2(-/-) mice had protracted motivational impairments after recovery from sickness suggesting a specific function for lymphocytes on the re-establishment of motivational states after activation of the innate immune system. The behavioral impairments in Rag2(-/-) mice were paralleled by an elevation in plasma corticosterone after behavioral tests. These results provide evidence that the absence of adaptive immunity may be associated with emotional deficits during inflammation and suggest that depressive states associated with medical illness may be mediated in part by impaired lymphocyte responses.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  8 / 449974 MEDLINE  
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[PMID]: 25815811
[Au] Autor:Christophe C; Müller S; Rodrigues M; Petit AE; Cattiaux P; Dupré L; Gadat S; Valitutti S
[Ad] Address:Institut de Mathématiques de Toulouse, CNRS UMR 5219, Toulouse, France; INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Section Dynamique Moléculaire des Interactions Lymphocytaires, Toulouse, France; Université Toulouse III Paul Sabatier, Toulouse, France....
[Ti] Title:A biased competition theory of cytotoxic T lymphocyte interaction with tumor nodules.
[So] Source:PLoS One;10(3):e0120053, 2015.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The dynamics of the interaction between Cytotoxic T Lymphocytes (CTL) and tumor cells has been addressed in depth, in particular using numerical simulations. However, stochastic mathematical models that take into account the competitive interaction between CTL and tumors undergoing immunoediting, a process of tumor cell escape from immunesurveillance, are presently missing. Here, we introduce a stochastic dynamical particle interaction model based on experimentally measured parameters that allows to describe CTL function during immunoediting. The model describes the competitive interaction between CTL and melanoma cell nodules and allows temporal and two-dimensional spatial progression. The model is designed to provide probabilistic estimates of tumor eradication through numerical simulations in which tunable parameters influencing CTL efficacy against a tumor nodule undergoing immunoediting are tested. Our model shows that the rate of CTL/tumor nodule productive collisions during the initial time of interaction determines the success of CTL in tumor eradication. It allows efficient cytotoxic function before the tumor cells acquire a substantial resistance to CTL attack, due to mutations stochastically occurring during cell division. Interestingly, a bias in CTL motility inducing a progressive attraction towards a few scout CTL, which have detected the nodule enhances early productive collisions and tumor eradication. Taken together, our results are compatible with a biased competition theory of CTL function in which CTL efficacy against a tumor nodule undergoing immunoediting is strongly dependent on guidance of CTL trajectories by scout siblings. They highlight unprecedented aspects of immune cell behavior that might inspire new CTL-based therapeutic strategies against tumors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0120053

  9 / 449974 MEDLINE  
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[PMID]: 25463533
[Au] Autor:Sombetzki M; Fuchs CD; Fickert P; Österreicher CH; Mueller M; Claudel T; Loebermann M; Engelmann R; Langner C; Sahin E; Schwinge D; Guenther ND; Schramm C; Mueller-Hilke B; Reisinger EC; Trauner M
[Ad] Address:Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock, Germany....
[Ti] Title:24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis.
[So] Source:J Hepatol;62(4):871-8, 2015 Apr.
[Is] ISSN:1600-0641
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND & AIMS: Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection. METHODS: Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro. RESULTS: UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect. CONCLUSIONS: This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 449974 MEDLINE  
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[PMID]: 25742476
[Au] Autor:Karakhanova S; Ryschich E; Mosl B; Harig S; Jäger D; Schmidt J; Hartwig W; Werner J; Bazhin AV
[Ad] Address:Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany....
[Ti] Title:Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma.
[So] Source:Br J Cancer;112(6):1027-36, 2015 Mar 17.
[Is] ISSN:1532-1827
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes. METHODS: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan-Meier method. RESULTS: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8(+) T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3(+) and effector-memory CD8(+) blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3(+) and CD8(+) cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3(+) lymphocytes, effCD8(+) T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy. CONCLUSIONS: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1503
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/bjc.2015.72


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