ABSTRACT
Cardiovascular diseases represent the first cause of mortality in the world. Various exploration methods exist to prevent and diagnose them. Among them, cardiac scintigraphy holds a predominant place. There are various equipments and procedures for its realization. We compared the practical aspects of using a conventional Anger camera (Symbia, Siemens) according to a two-days examination protocol with a dedicated cardio CzT camera (D-Spect, Spectrum Dynamics) according to a two-days protocol and a 360°SPECT/CT CzT camera (Veriton, Spectrum Dynamics) according to a one-day protocol. The use of CzT detectors allows a reduction of the activity injected to the patient and of the acquisition time in order to make this examination faster and less irradiating for the patient.
Les maladies cardiovasculaires représentent la première cause de mortalité dans le monde. Diverses méthodes d'exploration existent afin de les dépister et les diagnostiquer. Parmi elles, la scintigraphie cardiaque tient une place prépondérante. Il existe différents équipements et procédures pour sa réalisation. Nous avons comparé les aspects pratiques de la réalisation de l'examen avec une caméra d'Anger conventionnelle (Symbia, Siemens) selon un protocole d'examen en deux jours avec une caméra CzT cardio-dédiée (D-Spect, Spectrum Dynamics) selon un protocole en deux jours et une caméra 360°SPECT/CT CzT (Veriton, Spectrum Dynamics) selon un protocole en un jour. L'utilisation de détecteurs CzT permet une réduction de l'activité injectée au patient et des temps d'acquisition.
Subject(s)
Coronary Artery Disease , Myocardial Perfusion Imaging , Humans , Coronary Artery Disease/diagnostic imaging , Myocardial Perfusion Imaging/methods , Inventions , Tomography, Emission-Computed, Single-Photon/methods , Gamma CamerasSubject(s)
B-Lymphocytes/immunology , Celiac Disease/immunology , Intestinal Mucosa/immunology , Intestines/immunology , Intestines/pathology , Animals , Atrophy , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Disease Models, Animal , Glutens/adverse effects , HLA-DQ Antigens/immunology , Interferon-gamma/immunology , Mice , Protein Glutamine gamma Glutamyltransferase 2/immunologyABSTRACT
Coeliac disease is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that occurs in a subset of genetically susceptible individuals who express either the HLA-DQ8 or HLA-DQ2 haplotypes1,2. The need to develop non-dietary treatments is now widely recognized3, but no pathophysiologically relevant gluten- and HLA-dependent preclinical model exists. Furthermore, although studies in humans have led to major advances in our understanding of the pathogenesis of coeliac disease4, the respective roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in the development of tissue damage, have not been directly demonstrated. Here we describe a mouse model that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that is characteristic of active coeliac disease, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten. Overexpression of IL-15 in both the epithelium and the lamina propria is required for the development of villous atrophy, which demonstrates the location-dependent central role of IL-15 in the pathogenesis of coeliac disease. In addition, CD4+ T cells and HLA-DQ8 have a crucial role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell lysis. We also demonstrate a role for the cytokine interferon-γ (IFNγ) and the enzyme transglutaminase 2 (TG2) in tissue destruction. By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies.
Subject(s)
Celiac Disease/immunology , Celiac Disease/pathology , Glutens/immunology , HLA-DQ Antigens/immunology , Interleukin-15/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Female , HLA-DQ Antigens/genetics , Humans , Interferon-gamma/immunology , Interleukin-15/genetics , Male , Mice , Mice, Transgenic , Microfilament Proteins/genetics , Microfilament Proteins/metabolismABSTRACT
Forkhead box O (FOXO) transcription factors favor both T cell quiescence and trafficking through their control of the expression of genes involved in cell cycle progression, adhesion, and homing. In this article, we report that the product of the fam65b gene is a new transcriptional target of FOXO1 that regulates RhoA activity. We show that family with sequence similarity 65 member b (Fam65b) binds the small GTPase RhoA via a noncanonical domain and represses its activity by decreasing its GTP loading. As a consequence, Fam65b negatively regulates chemokine-induced responses, such as adhesion, morphological polarization, and migration. These results show the existence of a new functional link between FOXO1 and RhoA pathways, through which the FOXO1 target Fam65b tonically dampens chemokine-induced migration by repressing RhoA activity.
