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Background & Aims: Endoscopic tri-modal imaging (ETMI) incorporates high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow band imaging (NBI). A recent uncontrolled study found that ETMI improved the detection of high-grade dysplasia (HGD) and early carcinoma (Ca) in Barrett's esophagus (BE). The aim was to compare ETMI with standard video endoscopy (SVE) for the detection of HGD/Ca with the use of a randomized cross-over design., Methods: Patients referred for work-up of inconspicuous HGD/Ca were eligible and underwent both SVE and ETMI in randomized order within an interval of 6-12 weeks. During ETMI, inspection with HRE was followed by AFI. Detected lesions were inspected in detail with NBI and biopsied, followed by random biopsies. During SVE, any visible lesion was biopsied followed by random biopsies., Results: Eighty-seven patients with BE underwent ETMI and SVE. No significant difference was observed in overall histologic yield between ETMI and SVE. ETMI had a significantly higher targeted yield compared with SVE because of AFI. However, the yield of targeted biopsies of ETMI was significantly inferior to the overall yield of SVE. Detailed inspection with NBI reduced the false-positive rate of HRE + AFI from 71% to 48% but misclassified 17% of HGD/Ca lesions as not suspicious., Conclusions: ETMI statistically significant improves the targeted detection of HGD/Ca compared with SVE. Subsequent characterization of lesions with NBI appears to be of limited value. At this stage, ETMI cannot replace random biopsies for detection of lesions or targeted biopsies for characterization of lesions in a high-risk population., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Modifying the afferent blood supply to the liver does not change the zonal expression pattern of hepatic enzymes in the rat., Methods: We used pulmonary trunk banding (PTB) to study the effect of an efferent hindrance of blood flow on hepatic architecture and zonation of gene expression., Results: Most PTB rats developed right ventricular hypertrophy and congestive heart failure. The hepatic response to PTB developed concomitantly with the decline in heart function. Enzyme expression in the periportal region was not affected, but the pericentral rim of hepatocytes expressing glutamine synthetase, ornithine aminotransferase, and NADPH cytochrome P-450 reductase (CYPred) first declined in diameter, then became discontinuous, and finally disappeared. Meanwhile, ornithine aminotransferase and especially CYPred, became re-expressed in the periportal zone. These changes occurred without appreciable cell death or fibrotic changes; the expression of fibronectin and alpha-smooth muscle actin increased perisinusoidally, but that of collagen did not. Electron microscopic analysis revealed normal fenestration of the sinusoidal endothelial cells without detectable deposition of basement membrane material, but both the width of the space of Disse and the length and number of hepatic microvilli were significantly reduced, implying a decreased flow of fluid in the space of Disse., Conclusions: The reprogramming of gene expression in livers with a postsinusoidal hindrance of blood flow results from declining access of the hepatocytes to intrasinusoidal signal-transduction molecules and suggest that the impaired biotransformation that accompanies right ventricular failure is caused by a central-to-portal shift in expression of the corresponding enzymes.

Background & Aims: Regulatory CD4(+) cells secreting the anti-inflammatory cytokine interleukin (IL)-10 play a key role in maintaining the immune balance in the intestinal mucosa. In this study we engineered primary CD4(+) cells to express IL-10 and investigated the efficacy of this approach in offering protection against experimental colitis., Methods: Spleen-derived CD4(+) cells were transduced by using a retroviral vector to simultaneously express IL-10 and green fluorescent protein (GFP). The therapeutic benefit of CD4(+) cells transduced with IL-10 GFP was studied in experimental colitis, induced by transfer of CD45RB(high) CD4(+) cells to severe combined immunodeficient mice, and in acute trinitrobenzene sulfonic acid (TNBS)-induced colitis., Results: Transferred engineered GFP fluorescent cells were detected for at least 15 weeks in peripheral blood, spleens, colon, and lymph nodes draining the intestine of recipient SCID mice. IL-10-GFP CD4(+) cells prevented CD45RB(high)-induced transfer colitis effectively, whereas no effect was observed after transfer of nontransduced CD4(+) cells. IL-10-GFP CD45RB(high) CD4(+) cells lost the capacity to induce colitis. By contrast, no therapeutic benefit was observed in TNBS-induced colitis., Conclusions: Primary murine CD4(+) cells that were engineered to express IL-10 by retroviral transduction act as regulatory cells in CD45RB(high)-induced transfer colitis. This approach may induce long-term maintenance of mucosal immune homeostasis in Crohn's disease.

Background & Aims: Gastric epithelial renewal is an asymmetric process. A stem cell located halfway up the tubular unit gives rise to both a basal gland region and a luminal pit compartment, but the mechanisms responsible for the maintenance of this asymmetry are obscure. We investigated whether Sonic hedgehog (Shh), an established polarizing signal protein during development, is expressed and functional in the adult human and murine stomach., Methods: Expression of Shh and putative transcriptional targets was investigated using immunoblot and immunohistochemistry. Mice were treated with the Shh inhibitor cyclopamine and examined for expression levels of Shh targets and proliferation of gastric epithelial cells., Results: Shh was expressed in the stomach. In cyclopamine-treated mice, we observed decreased expression of HNF3beta, Islet (Isl)-1 and BMP4, 3 putative Shh target genes. Inhibition of Shh markedly enhanced gastric epithelial proliferation and affected the cell cycle of gastric epithelial gland cells, whereas pit cells remained unaffected., Conclusions: Shh controls the expression of at least 3 factors important for epithelial differentiation and is a negative regulator of gastric gland cell proliferation. Shh is a candidate polarizing signal in the maintenance of gastric pit-gland asymmetry.

A retrospective study of 7 adult patients (6 with severe, long-standing constipation and 1 with chronic idiopathic intestinal pseudoobstruction) was carried out to test the diagnostic potential of the antineurofilament monoclonal antibody NF2F11. In 4 of the cases of constipation and in the 1 case of pseudoobstruction, paraffin sections of resected colon revealed an anomaly in that the axon bundles of both plexus systems remained unstained. This picture differed from that found in the control population. The results are discussed in relation to previous studies of congenital neurogenic abnormalities of the digestive tract in children.