Cyclosporine a directly affects human and mouse b cell migration in vitro by disrupting a hIF-1 αdependent, o2 sensing, molecular switch.

BACKGROUND: Hypoxia is a potent molecular signal for cellular metabolism, mitochondrial function, and migration. Conditions of low oxygen tension trigger regulatory cascades mediated via the highly conserved HIF-1 α post-translational modification system. In the adaptive immune response, B cells (Bc) are activated and differentiate under hypoxic conditions within lymph node germinal centers, and subsequently migrate to other compartments. During migration, they traverse through changing oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the peripheral blood. Interestingly, the calcineurin inhibitor cyclosporine A is known to stimulate prolyl hydroxylase activity, resulting in HIF-1 α destabilization and may alter Bc responses directly. Over 60% of patients taking calcineurin immunosuppressant medications have hypo-gammaglobulinemia and poor vaccine responses, putting them at high risk of infection with significantly increased morbidity and mortality. RESULTS: We demonstrate that O 2 tension is a previously unrecognized Bc regulatory switch, altering CXCR4 and CXCR5 chemokine receptor signaling in activated Bc through HIF-1 α expression, and controlling critical aspects of Bc migration. Our data demonstrate that calcineurin inhibition hinders this O 2 regulatory switch in primary human Bc. CONCLUSION: This previously unrecognized effect of calcineurin inhibition directly on human Bc has significant and direct clinical implications.

Effects of contrast-enhancement on diffusion weighted imaging and apparent diffusion coefficient measurements in 3-T magnetic resonance imaging of breast lesions.

Background The effect of gadolinium-based contrast agents on diffusion-weighted imaging (DWI) measurements of breast lesions is still not clear. Purpose To investigate gadolinium effects on DWI and apparent diffusion coefficient (ADC) in breast lesions and normal parenchyma with 3 Tesla contrast-enhanced MRI. Material and Methods Pre- and post-contrast DWI (b = 0 and b = 1000 s/mm2) were acquired in 47 patients. Measured ADC values, pre- and post-contrast T2 signal intensity (T2 SI) and contrast-to-noise ratio (CNR) were compared with Wilcoxon signed-rank and rank-sum test ( P < 0.05). Results Post-contrast ADC was reduced only in malignant lesions (-34%), T2 SI was reduced both in malignant (-50%) and benign (-36%) lesions. Post-contrast CNR was reduced in all groups except for benign lesions. Conclusion Gadolinium-based contrast agent causes a significant reduction in ADC values of malignant breast lesions.

Role of 3.0 Tesla magnetic resonance hysterosalpingography in the diagnostic work-up of female infertility.

BACKGROUND: Imaging evaluation plays a crucial role in the diagnostic work-up of female infertility. In recent years, the possibility to evaluate tubal patency using 1.5 Tesla magnetic resonance (1.5T MR) has been studied. PURPOSE: To assess the feasibility of 3.0 Tesla magnetic resonance (3.0T MR) hysterosalpingography and its role in the diagnostic work-up of female infertility and to evaluate if this fast "one-stop-shop" imaging approach should be proposed as a first-line examination. MATERIAL AND METHODS: A total of 116 infertile women were enrolled in this prospective study; all underwent 3.0T MR hysterosalpingography. After standard imaging of the pelvis, tubal patency was assessed by acquiring 3D dynamic time-resolved T1-weighted (T1W) sequences during manual injection of 4-5 mL of contrast solution consisting of gadolinium and normal sterile saline. Images were evaluated by two radiologists with different experience in MR imaging (MRI). RESULTS: The examination was successfully completed in 96.5% of cases, failure rate was 3.5%. Dynamic sequences showed bilateral tubal patency in 64.3%, unilateral tubal patency in 25.9%, and bilateral tubal occlusion in 9.8%. Extratubal abnormalities were found in 69.9% of patients. Comprehensive analysis of morphological and dynamic sequences showed extratubal abnormalities in 43.1% of patients with bilateral tubal patency. CONCLUSION: 3.0T MR hysterosalpingography is a feasible, simple, fast, safe, and well-tolerated examination, which allows evaluation of tubal patency and other pelvic causes of female infertility in a single session, and it may thus represent a "one-stop-shop" solution in female infertility diagnostic work-up.

Correlation between 3T apparent diffusion coefficient values and grading of invasive breast carcinoma.

PURPOSE: The aim of this study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0T (3T) magnetic resonance diffusion-weighted imaging (DWI) varied according to the grading of invasive breast carcinoma. MATERIALS AND METHODS: A total of 92 patients with 96 invasive breast cancer lesions were enrolled; all had undergone 3T magnetic resonance imaging (MRI) for local staging. All lesions were confirmed by histological analysis, and tumor grade was established according to the Nottingham Grading System (NGS). MRI included both dynamic contrast-enhanced and DWI sequences, and ADC value was calculated for each lesion. ADC values were compared with NGS classification using the Mann-Whitney U and the Kruskal-Wallis H tests. Grading was considered as a comprehensive prognostic factor, and Rho Spearman test was performed to determine correlation between grading and tumor size, hormonal receptor status, HER2 expression and Ki67 index. Pearson's Chi square test was carried out to compare grading with the other prognostic factors. RESULTS: ADC values were significantly higher in G1 than in G3 tumors. No significant difference was observed when G1 and G3 were compared with G2. Tumor size, hormonal receptor status, HER2 expression and Ki67 index correlated significantly with grading but there was a significant difference only between G1 and G3 related to the ER and PR status, HER2 expression and Ki67 index. There was no statistically significant difference in lesion size between the two groups. CONCLUSION: ADC values obtained on 3T DWI correlated with low-grade (G1) and high-grade (G3) invasive breast carcinoma. 3T ADC may be a helpful tool for identifying high-grade invasive breast carcinoma.