Isolation and characterization of the ecdysone receptor and its heterodimeric partner ultraspiracle through development in Sciara coprophila.

Regulation of DNA replication is critical, and loss of control can lead to DNA amplification. Naturally occurring, developmentally regulated DNA amplification occurs in the DNA puffs of the late larval salivary gland giant polytene chromosomes in the fungus fly, Sciara coprophila. The steroid hormone ecdysone induces DNA amplification in Sciara, and the amplification origin of DNA puff II/9A contains a putative binding site for the ecdysone receptor (EcR). We report here the isolation, cloning, and characterizing of two ecdysone receptor isoforms in Sciara (ScEcR-A and ScEcR-B) and the heterodimeric partner, ultraspiracle (ScUSP). ScEcR-A is the predominant isoform in larval tissues and ScEcR-B in adult tissues, contrary to the pattern in Drosophila. Moreover, ScEcR-A is produced at amplification but is absent just prior. We discuss these results in relation to the model of ecdysone regulation of DNA amplification.

In vivo diagnostic accuracy of high-resolution microendoscopy in differentiating neoplastic from non-neoplastic colorectal polyps: a prospective study.

OBJECTIVES: High-resolution microendoscopy (HRME) is a low-cost, "optical biopsy" technology that allows for subcellular imaging. The purpose of this study was to determine the in vivo diagnostic accuracy of the HRME for the differentiation of neoplastic from non-neoplastic colorectal polyps and compare it to that of high-definition white-light endoscopy (WLE) with histopathology as the gold standard. METHODS: Three endoscopists prospectively detected a total of 171 polyps from 94 patients that were then imaged by HRME and classified in real-time as neoplastic (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory). RESULTS: HRME had a significantly higher accuracy (94%), specificity (95%), and positive predictive value (PPV, 87%) for the determination of neoplastic colorectal polyps compared with WLE (65%, 39%, and 55%, respectively). When looking at small colorectal polyps (less than 10 mm), HRME continued to significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98% vs. 40%) and PPV (92% vs. 55%). These trends continued when evaluating diminutive polyps (less than 5 mm) as HRME's accuracy (95%), specificity (98%), and PPV (93%) were all significantly greater than their WLE counterparts (62%, 41%, and 53%, respectively). CONCLUSIONS: In conclusion, this in vivo study demonstrates that HRME can be a very effective modality in the differentiation of neoplastic and non-neoplastic colorectal polyps. A combination of standard white-light colonoscopy for polyp detection and HRME for polyp classification has the potential to truly allow the endoscopist to selectively determine which lesions can be left in situ, which lesions can simply be discarded, and which lesions need formal histopathologic analysis.

Clinical outcomes of patients with ulcerative colitis and co-existing Clostridium difficile infection.

BACKGROUND: The incidence of Clostridium difficile infection is increasing in the United States. The aim of our investigation is to compare short-term and long-term outcomes of patients admitted with an ulcerative colitis (UC) flare and co-existent C. difficile infection to those of non-infected patients. METHODS: A historical cohort study was undertaken examining admissions at Mount Sinai Hospital between June 2004 and June 2005 using ICD-9 criteria for UC. Charts were abstracted for those patients for whom C. difficile testing was performed. RESULTS: Of 288 admissions, 99 charts met the inclusion criteria. Fifty-two patients were C. difficile-negative and 47 were positive. Demographic data and laboratory values upon admission did not differ between the two groups. Patients who were C. difficile-positive had significantly more UC-related hospitalizations and emergency room visits in the year following initial admission (58 visits vs. 27, P = 0.001 and eight visits vs. 1 visit (P = 0.012), respectively). One year following the index admission, C. difficile patients had significantly higher rates of colectomy compared to C. difficile-negative patients (44.6% vs. 25%, P = 0.04). Length of hospitalization (11.7 vs. 11 days), use of cyclosporine therapy during index admission (48% vs. 47% of patients), and percentage requiring colectomy at initial admission (23.4% vs. 13.5%) did not reach statistical significance. CONCLUSIONS: Our data suggest that patients presenting with a UC flare who are infected with C. difficile have worse long-term clinical outcomes than those that are C. difficile-negative. C. difficile testing should be performed for all patients presenting with UC flare. Further studies are warranted to elucidate how infection can alter the natural history of UC.

Endoscopic management of familial colonic neoplasia.

Heredity plays an important causative role in a large percentage of colorectal cancers. Clinical recognition of the hereditary polyposis syndromes, hereditary nonpolyposis colorectal cancer, and common familial colorectal cancer is essential because screening, surveillance, and treatment among affected individuals and their family members differs from that recommended for the general population. More intensive cancer screening and surveillance is required if premature death is to be avoided. Genetic testing is commercially available for most of the hereditary colorectal cancer syndromes and can greatly facilitate the management of patients if properly undertaken.

Infusion reactions and their management.

Infliximab therapy should be optimized to minimize immunogenicity, to prevent infusion reactions, and to maintain clinical response. Based on best available evidence, strategies include minimizing the formation of ATI by administering infliximab as a multidose induction therapy followed by scheduled maintenance regiment, the use of concurrent immunomodulators, and possibly premedicating with steroids. Infusion reaction are common and they can be managed using specific protocols outlined in this article.

Advances in the pathogenesis of inflammatory bowel disease.

Most people do not develop inflammatory bowel disease (IBD) in spite of the density of the commensal flora. In the past few years, several areas of gut mucosal immunology have emerged that will permit advances in the management of IBD at the bedside. The commensal flora is only beginning to be fully appreciated as another metabolic organ in the body. Innate immunity as it relates to the gut has complemented our understanding of the adaptive immune response. The most important susceptibility gene described for Crohn's disease, the NOD2 gene, participates in the innate immune response to pathogens. Patients carrying NOD2 mutations have an increased adaptive immune response to commensal organisms as measured by higher titers of antimicrobial antibodies, such as anti-CBir and anti-Saccharomyces cerevisiae antibodies. Toll-like receptors expressed by antigen-presenting cells (APCs) in the gut and intestinal epithelial cells also play a role in recognition of intestinal flora. Within the APC category, dendritic cells link the innate and adaptive immune systems and shape the nature of the adaptive immune response to commensal bacteria. With respect to adaptive immunity, a new signaling pathway involving a distinct helper CD4 T-cell subset producing interleukin-17 may become a target for the treatment of chronic inflammatory diseases. This review focuses on developments likely to culminate in advances in patient care.