Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor kappaB (NF-kappaB) and antibacterial defenses, but CD clinical specimens display elevated NF-kappaB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-kappaB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1beta (IL-1beta). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion.

BackgroundMicrobubbles and contrast-enhanced ultrasound (CEUS) is a new technique for locating sentinel lymph node (SLN). The aim of this study is to explore the feasibility of SLNs tracing by CEUS using microbubbles in breast cancer patients and the value of enhancing patterns in diagnosing lymph nodes metastases.MethodsA clinical trial was registered (trial registration: ChiCTR-DDT-13003778). One hundred and one consecutive consenting patients with breast cancer undergoing SLN biopsy were enrolled. Before the surgery, microbubble was injected periareolarly. Lymphatic drainage pathway was detected by CEUS, and guidewire was deployed to locate the SLN before the operation. Blue dye was also used to help in tracing sentinel lymph node during the operation. The identification rate and the accuracy rate were recorded. Enhancing patterns of lymph nodes were recorded and compared with the pathological diagnosis.ResultsOf the 101 cases, SLNs in 99 cases were successfully identified by at least one tracer, including 98 cases identified by CEUS and 97 cases by blue dye. There was no significant difference between the two methods (P = 0.705). Guidewires were deployed successfully in all 98 cases, and the localized SLNs were all isolated successfully in the following operations. The status of SLNs isolated by CEUS was completely identical to that of the whole axillary lymph node while 7.1 % cases were misdiagnosed as negative by blue dye method. The sensitivity of predicting SLNs metastases by CEUS enhancing pattern was 81.8 %, the specificity was 86.2 %, and the positive and negative predictive values were 75.0 and 90.3 %, respectively.ConclusionsMicrobubbles and CEUS are feasible approaches for SLN identification. The enhancing patterns on CEUS may be helpful to recognize the metastasizing SLNs. This novel method may be a promising technique for the clinical application.

Purpose Recent MRI studies have revealed heterogeneous magnetic susceptibility contrasts in multiple sclerosis (MS) lesions. Due to its sensitivity to disease related iron and myelin changes, magnetic susceptibility-based measures may better reflect some pathological features of MS lesions. Hence we sought to characterize MS lesions using combined R2* mapping and quantitative susceptibility mapping (QSM). Materials and Methods Three hundred and six MS lesions were selected from 24 MS patients who underwent 7T MR. Maps of R2*, frequency and quantitative susceptibility were calculated using acquired multi-echo gradient echo (GRE) phase data. Lesions were categorized based on their image intensity or their anatomical locations. R2* and susceptibility values were quantified in each lesion based on manually drawn lesion masks and compared between lesion groups showing different contrast patterns. Correlations between R2* and susceptibility were also tested in these lesion groups. Results In 38% of selected lesions the frequency map did not show the same contrast pattern as the susceptibility map. While most lesions (93%) showed hypointensity on R2*, the susceptibility contrast in lesions varied; with 40% being isointense and 58% being hyperintense in the lesion core. Significant correlations (r=0.31, p<0.001) between R2* and susceptibility were found in susceptibility hyperintense lesions, but not in susceptibility isointense lesions. In addition, a higher proportion (74%) of periventricular lesions was found to be susceptibility hyperintense as compared to subcortical (53%) or juxtacortical (38%) lesions. Conclusion Combining R2* and QSM is useful to characterize heterogeneity in MS lesions.