Publications

In the thymus, developing T cells that react against self-antigens with high affinity are deleted in the process of negative selection. An essential component of this process is the display of self-antigens, including those whose expression are usually restricted to specific tissues, to developing T cells within the thymus. The Autoimmune Regulator (Aire) gene plays a crucial role in the expression of tissue specific self-antigens within the thymus, and disruption of Aire function results in spontaneous autoimmunity in both humans and mice. Recent advances have been made in our understanding of how Aire influences the expression of thousands of tissue-specific antigens in the thymus. Additional roles of Aire, including roles in chemokine and cytokine expression, have also been revealed. Factors important in the differentiation of Aire-expressing medullary thymic epithelial cells have been defined. Finally, the identity of antigen presenting cells in negative selection, including the role of medullary thymic epithelial cells in displaying tissue specific antigens to T cells, has also been clarified.

BACKGROUND

Most studies of catheter ablation for the treatment of ventricular tachycardia (VT) are relatively small observational trials.

OBJECTIVE

The purpose of this study was to define the relative risk of VT recurrence in patients undergoing catheter ablation as an adjunct to medical therapy versus medical therapy alone in a pooled analysis of controlled studies.

METHODS

Randomized and nonrandomized controlled trials of patients who underwent adjunctive catheter ablation of VT versus medical therapy alone were sought. MEDLINE, EMBASE, the Cochrane central register of controlled trials (CENTRAL), and Web of Science were searched from 1965 to July 2010. Supplemental searches included Internet resources, reference lists, and reports of arrhythmia experts. Three authors independently reviewed and extracted the data regarding baseline characteristics, ablation methodology, medical therapy, complications, VT recurrences, mortality, and study quality.

RESULTS

Five studies were included totaling 457 participants with structural heart disease. Adjunctive catheter ablation was performed in 58% of participants, whereas 42% received medical therapy alone for VT. Complications of catheter ablation included death (1%), stroke (1%), cardiac perforation (1%), and complete heart block (1.6%). Using a random-effects model, a statistically significant 35% reduction in the number of patients with VT recurrence was noted with adjunctive catheter ablation (P<.001). There was no statistically significant difference in mortality.

CONCLUSIONS

Catheter ablation as an adjunct to medical therapy reduces VT recurrences in patients with structural heart disease and has no impact on mortality.

Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. Here, we demonstrate that the IL-4/STAT6 immune axis, a key pathway in helminth immunity and allergies, controls peripheral nutrient metabolism and insulin sensitivity. Disruption of signal transducer and activator of transcription 6 (STAT6) decreases insulin action and enhances a peroxisome proliferator-activated receptor α (PPARα) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPARα-regulated program of nutrient catabolism and attenuating adipose tissue inflammation. These findings have thus identified an unexpected molecular link between the immune system and macronutrient metabolism, suggesting perhaps the coevolution of these pathways occurred to ensure access to glucose during times of helminth infection.