IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2. The aim of this study was to analyze IL-22 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal epithelial cells (IEC). Expression studies were performed by RT-PCR. Signal transduction was analyzed by Western blot experiments, cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and Fas-induced apoptosis by flow cytometry. IEC migration was studied in wounding assays. The IEC lines Caco-2, DLD-1, SW480, HCT116, and HT-29 express both IL-22 receptor subunits IL-22R1 and IL-10R2. Stimulation with TNF-alpha, IL-1beta, and LPS significantly upregulated IL-22R1 without affecting IL-10R2 mRNA expression. IL-22 binding to its receptor complex activates STAT1/3, Akt, ERK1/2, and SAPK/JNK MAP kinases. IL-22 significantly increased cell proliferation (P = 0.002) and phosphatidylinsitol 3-kinase-dependent IEC cell migration (P < 0.00001) as well as mRNA expression of TNF-alpha, IL-8, and human beta-defensin-2. IL-22 had no effect on Fas-induced apoptosis. IL-22 mRNA expression was increased in inflamed colonic lesions of patients with Crohn's disease and correlated highly with the IL-8 expression in these lesions (r = 0.840). Moreover, IL-22 expression was increased in murine dextran sulfate sodium-induced colitis. IEC express functional receptors for IL-22, which increases the expression of proinflammatory cytokines and promotes the innate immune response by increased defensin expression. Moreover, our data indicate intestinal barrier functions for this cytokine-promoting IEC migration, which suggests an important function in intestinal inflammation and wound healing. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and IEC migration.

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Dynamic susceptibility contrast MRI (DSC-MRI) is the current standard for the measurement of Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV), but it is not suitable for the measurement of Extraction Flow (EF) and may not allow for absolute quantification. The objective of this study was to develop and evaluate a methodology to measure CBF, CBV, and EF from T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). A twocompartment modeling approach was developed, which applies both to tissues with an intact and with a broken Blood-BrainBarrier (BBB). The approach was evaluated using measurements in normal grey matter (GM) and white matter (WM) and in tumors of 15 patients. Accuracy and precision were estimated with simulations of normal brain tissue. All tumor and normal tissue curves were accurately fitted by the model. CBF (mL/100 mL/min) was 82 ± 21 in GM and 23 ± 14 in WM, CBV (mL/100 mL) was 2.6 ± 0.8 in GM and 1.3 ± 0.4 in WM. EF (mL/100 mL/min) was close to zero in GM (−0.009 ± 0.05) and WM (−0.03 ± 0.08). Simulations show an overlap between CBF values of WM and GM, which is eliminated when Contrast-to-Noise (CNR) is improved. The model provides a consistent description of tracer kinetics in all brain tissues, and an accurate assessment of perfusion and permeability in reference tissues. The measurement sequence requires optimization to improve CNR and the precision in the perfusion parameters. With this approach, DCE-MRI presents a promising alternative to DSC-MRI for quantitative bolustracking in the brain.

The appropriate staging of malignant tumors is increasingly important as new therapeutic strategies develop. Because metastatic involvement of the liver in extrahepatic malignant disease may signiˆcantly change therapeutic approach, it is important to rule out such involvement with high conˆdence. Moreover, the diŠerentiation between incidental benign lesions, such as hemangioma, focal nodular hyperplasia (FNH), or adenoma, is of high interest. Magnetic resonance (MR) imaging has proved reliable for diagnostic work-up of the liver. Liver-speciˆc contrast agents have been especially helpful in detecting and precisely characterizing focal liver lesions, but the use of these agents has been limited because it has not been possible to perform both proper vascular phase and liver-speciˆc phase within a reasonable time frame and in a single examination after a single injection of contrast agent. However, the hepatobiliary contrast agent gadolinium-ethoxybenzyl (Gd-EOB)-DTPA now allows combined dynamic imaging and hepatocyte-speciˆc imaging in one examination. Gd-EOB-DTPA can be injected as a bolus and shows the enhancement characteristics and vascularity of liver lesions. In the delayed phase, which is acquired most appropriately 20 min after injection, Gd-EOB-DTPA is taken up selectively by functioning hepatocytes. Thus, malignant liver lesions, e.g. metastases, are spared from contrast uptake of the surrounding liver parenchyma. These lesions are hypointense in contrast to the surrounding bright liver. We review the current literature and present a practical approach to Gd-EOB-enhanced MR imaging using imaging examples of patients with liver metastases.

Imaging findings of MR lymphangiography and lymphoscintigraphy show a clear concordance. With lymphoscintigraphy, better visualization of inguinal lymph nodes was achieved, whereas with MR lymphangiography, better depiction of lymph vessels and morphologic features of lymph vessel abnormalities were achieved.

Complete T-cell activation requires two distinct signals, one delivered via the T-cell receptor, and the second "co-stimulatory" signal through CD28/B7 ligation. Previous studies showed that the blockade of CD28/B7 ligation alters differentiation of Th1/Th2 lymphocyte subsets in vitro and in vivo. The present study was designed to determine the effect of a CD28/B7 antagonist (CTLA4Ig) on Th1/Th2 development in Schistosoma mansoni-sensitized and airway-challenged mice. Treatment of mice with CTLA4Ig beginning 1 wk after sensitization abolished airway responsiveness to intravenous methacholine determined 96 h following antigen challenge. We also found a significant reduction in bronchoalveolar lavage (BAL) eosinophilia, and reduced peribronchial eosinophilic infiltration and mucoid-cell hyperplasia. Furthermore, CTLA4Ig treatment significantly decreased interleukin (IL)-4 and IL-5 content in BAL fluid in vivo, and the production of IL-5 by lung lymphocytes stimulated with soluble egg antigen (SEA) in vitro. In contrast, the content of interferon-gamma in BAL fluid and supernatant from SEA-stimulated lung lymphocytes from CTLA4Ig-treated mice was increased significantly compared with untreated animals. Thus, CTLA4Ig inhibits eosinophilic airway inflammation and airway hyperresponsiveness in S. mansoni-sensitized and airway-challenged mice, most likely due to attenuated secretion of Th2-type cytokines and increased secretion of Th1-type cytokines.

Using parallel imaging, DTI measurements of the kidneys are feasible within a single breath-hold with good discrimination between cortex and medulla. Parallel imaging allows more slices and a superior resolution. DTI measurements of the kidney allows visualization of medullary flow, in pathology ADC and FA were altered. Further investigations will be required to evaluate the role of DTI for studying and monitoring renal ultrastructure.

Diffusion tensor imaging of the kidney at 3T is feasible and yields significantly higher SNR and CNR. FA and ADCs do not significantly differ from 1.5T. Number of b-values influences ADC-values. Acquisitions in 12 directions provide lower cortical FA-values. We recommend a respiratory-triggered protocol because of improved image quality and reproducibility.