Search results for " Models"
showing 10 items of 4240 documents
A Critical Regulatory Role of Leucin Zipper Transcription Factor c-Maf in Th1-Mediated Experimental Colitis
2004
Abstract In this study, we investigated the role of c-Maf, a transcription factor known to induce IL-4 production, in inflammatory bowel diseases and experimental colitis. Although Crohn′s disease (CD) is associated with low IL-4 production by T-bet-expressing Th1 cells in the lamina propria, surprisingly a higher expression of c-Maf in these cells was found as compared with control patients. The relevance of this finding was further evaluated in an animal model of CD induced by adoptive transfer of CD4+CD62L+ T cells in RAG-deficient mice. In this Th1-mediated model, an increase of c-Maf-expressing T lymphocytes in the lamina propria over time was observed. Interestingly, adoptive transfer…
Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation.
2012
Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse. Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants and the induction of T-cell tolerance. However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms. Here we establish an effective ACT protocol in a genetically engineered mouse melanoma model that recapitulates tumour regression, remission and relapse as seen in patients. We report the unexpected observation that melanoma…
IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells
2007
Regulatory T (T(reg)) cells play a key role in the maintenance of the immune system homeostasis. T(reg) cells can be generated in the periphery under control of TGF-beta, a cytokine involved in the negative control of the immune system. However, TGF-beta cooperates with IL-6 in the generation of Th17 cells, a novel class of effector cells involved in numerous inflammatory diseases, including colitis. Therefore, TGF-beta emerges as a mediator of both anti-inflammatory and pro-inflammatory processes, depending on the local cytokine milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by T cells and involved in the pathogenesis of immune-mediated diseases, prevents the TGF-beta-d…
Therapeutic Vaccination of Hematopoietic Cell Transplantation Recipients Improves Protective CD8 T-Cell Immunotherapy of Cytomegalovirus Infection
2021
Reactivation of latent cytomegalovirus (CMV) endangers the therapeutic success of hematopoietic cell transplantation (HCT) in tumor patients due to cytopathogenic virus spread that leads to organ manifestations of CMV disease, to interstitial pneumonia in particular. In cases of virus variants that are refractory to standard antiviral pharmacotherapy, immunotherapy by adoptive cell transfer (ACT) of virus-specific CD8+ T cells is the last resort to bridge the “protection gap” between hematoablative conditioning for HCT and endogenous reconstitution of antiviral immunity. We have used the well-established mouse model of CD8+ T-cell immunotherapy by ACT in a setting of experimental HCT and mu…
Interleukin-7 or Interleukin-15 Enhances Survival ofMycobacterium tuberculosis-Infected Mice
2000
ABSTRACTBoth antigen-presenting cells and immune effector cells are required to effectively eradicate or containMycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive “cross talk” between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of α/β and γ/δ T cells. Here we show that either cytokine is able to enhance survival ofM. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival cou…
Outcomes of single versus double hormone receptor–positive breast cancer. A GEICAM/9906 sub-study
2018
Abstract Background Retrospective data suggest better outcomes for patients with double hormonal receptor (oestrogen [ER] and progesterone receptor [PgR])–positive (dHR+) early breast cancer, compared with single hormonal receptor–positive, sHR+, (ER+/PgR– or ER–/PgR+) disease. Here, we evaluate the classification according to intrinsic subtypes and clinical outcomes of sHR+ versus dHR+ in HER2-negative breast cancer patients enrolled in GEICAM/9906 study ( NCT00129922 ). Methods Archival tumours were retrieved retrospectively for the analysis of ER, PgR and HER2 status and classified into intrinsic subtypes using the PAM50 gene expression assay. Disease-free survival (DFS) and overall surv…
Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts
2022
BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country regi…
BODY SIZE AT BIRTH, CHILDHOOD GROWTH, HIP FRACTURES IN OLDER AGE
2017
Childhood growth has been linked with bone properties in adulthood, whereas less is known about the contribution of early growth to bone fracture risk. We investigated the association of body size at birth and childhood growth with hip fractures and pharmacotherapy for osteoporosis in older age. Men and women, born full term, from the Helsinki Birth Cohort Study (n = 8345) were followed until the age of 68 to 80 years. Height and weight from birth to 11 years were obtained from health care records and diagnoses of hip fractures and osteoporosis drug purchases from national registers. Independent associations of each age period were analyzed using Cox models adjusted for age, childhood and a…
Usefulness of N-terminal pro-B-type natriuretic peptide levels in predicting residual myocardial ischemia in patients with ST elevation acute myocard…
2007
N-terminal pro-b-type natriuretic peptide (NT pro-BNP) is a neurohormone synthesized predominantly in ventricular myocardium. In patients with symptoms of heart failure, elevation in NT pro-BNP accurately identifies ventricular dysfunction. However, NT pro-BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevation in NT pro-BNP. The study was aimed to determine whether NT pro-BNP elevations are associated with myocardial ischemia.One hundred and thirty patients (104 males, 26 females, mean age 61+12 years), with ST elevation acute myocardial …
Age at menopause predicts age at onset of Parkinson's disease.
2006
We investigated the association between age at onset of Parkinson's disease (PD) and fertile life characteristics in 145 women. Linear regression analyses showed a significant correlation between age at PD onset and age at menopause (P = 0.003), between age at PD onset and fertile life duration (P = 0.008), and a nonsignificant correlation between PD onset and cumulative duration of pregnancies (P = 0.23). These results support the possible role of estrogens in PD.