Monitoring the T cell response to genital tract infection

To date, it has not been possible to study antigen-specific T cell responses during primary infection of the genital tract. The low frequency of pathogen-specific T cells in a na?ve mouse makes it difficult to monitor the initial events after antigen encounter. We developed a system to examine the response of pathogen-specific T cells in the genital mucosa after intrauterine infection. We identified the protective CD4(+) T cell antigen Cta1 from Chlamydia trachomatis and generated T cell receptor (TCR) transgenic (tg) mice with specificity for this protein. By transferring TCR tg T cells into na?ve animals, we determined that Chlamydia-specific T cells were activated and proliferated in the lymph nodes draining the genital tract after primary intrauterine infection. Activated T cells migrated into the genital mucosa and secreted IFN-gamma. The development of Chlamydia-specific TCR tg mice provides an approach for dissecting how pathogen-specific T cells function in the genital tract.     

Prediction of postoperative myocardial infarction after suprainguinal bypass using the Vascular Quality Initiative Cardiac Risk Index

BackgroundThe Vascular Quality Initiative (VQI) Cardiac Risk Index (CRI) was developed to estimate the risk of postoperative myocardial infarction (POMI) for noncardiac vascular procedures. Whereas suprainguinal bypass carried the second highest odds of POMI, the performance of the all-procedure model declined when it was applied to the suprainguinal subset. We sought to improve the VQI CRI for application in this high-risk group undergoing open revascularization for aortoiliac occlusive disease.MethodsThe VQI Suprainguinal Bypass Registry was queried for elective procedures performed between January 2010 and March 2017. Logistic regression was used to create a model for estimating the risk of in-hospital POMI with preoperative variables including demographics, comorbidities, and planned inflow source. After adjustment for overfitting, internal validation was performed using both bootstrapping and 10-fold cross-validation methods.ResultsAmong 8157 procedures, the incidence of POMI was 3.2% (n = 258). After bootstrapping variable selection, age, graft inflow, preoperative stress test, American Society of Anesthesiologists class, indication for procedure, and coronary artery disease were chosen for inclusion as predictors in the final risk model. The final model demonstrated good discrimination (area under the curve = 0.725). On internal validation, the model discriminated well (area under the curve = 0.713), with good calibration (plot intercept = 0.0006 and slope = 1.001). Using this model, POMI risk estimates ranged from 0.6% to 30.4%.ConclusionsWhereas the incidence of POMI among all suprainguinal bypasses was 3%, model-based estimates ranged 50-fold, from 0.6% to 30.4%. This underscores the heterogeneity of this cohort and the need for patient-specific risk estimation. Although some of the strongest predictors were nonmodifiable (eg, age), the model provided specific estimates according to graft inflow and stress testing. This supraspecific VQI CRI module risk predictor may enhance preoperative counseling by influencing the decision to pursue preoperative stress testing and ultimately the type of revascularization strategy chosen.     

Added Value of Use of a Purified Protein Derivative-Based Enzyme-Linked Immunosorbent Spot Assay for Patients with Mycobacterium bovis BCG Infection after Intravesical BCG Instillations

In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma.     

Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures

BACKGROUND: Exenatide (exendin-4) is an incretin mimetic currently marketed as an antidiabetic agent for patients with type 2 diabetes. In preclinical models, a reduction in body weight has also been shown in low-fat-fed, leptin receptor-deficient rodents. OBJECTIVE: To more closely model the polygenic and environmental state of human obesity, we characterized the effect of exenatide on food intake and body weight in high-fat-fed, normal (those with an intact leptin signaling system) rodents. As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity. METHODS AND RESULTS: High-fat-fed C57BL/6 mice and Sprague-Dawley rats were treated with exenatide (3, 10 and 30 microg/kg/day) for 4 weeks via subcutaneously implanted osmotic pumps. Food intake and body weight were assessed weekly. At 4 weeks, body composition and plasma metabolic profiles were measured. Kaolin consumption and locomotor activity were measured in fasted Sprague-Dawley rats following a single intraperitoneal injection of exenatide (0.1-10 microg/kg). Exenatide treatment in mice and rats dose-dependently decreased food intake and body weight; significant reductions in body weight gain were observed throughout treatment at 10 and 30 microg/kg/day (P<0.05). Decreased body weight gain was associated with a significant decrease in fat mass (P<0.05) with sparing of lean tissue. Plasma cholesterol, triglycerides and insulin were also significantly reduced (P<0.05). Exenatide at 10 microg/kg significantly reduced food intake (P<0.05) but failed to induce kaolin intake. In general, locomotor activity was reduced at doses of exenatide that decreased food intake, although a slightly higher dose was required to produce significant changes in activity. CONCLUSION: Systemic exenatide reduces body weight gain in normal, high-fat-fed rodents, a model that parallels human genetic variation and food consumption patterns, and may play a role in metabolic pathways mediating food intake.