Identification and characterization of a novel zebrafish semaphorin

The semaphorin gene family contains numerous secreted and transmembrane proteins. Some of them function as the repulsive and attractive axon guidance molecules during development. Herein, we report the cloning and characterization of a novel member of zebrafish semaphorin gene, semaphorin 6E (sema6E). Sema6E is expressed predominantly in the nervous system during embryogenesis. Results also show that Sema6E binds Plexin-A1, but not other Plexins. Sema6E chemorepels not only dorsal root ganglion axons but also sympathetic axons. Therefore, Sema6E might utilize Plexin-A1 as a receptor to repel axons of the specific types during development.     

Spatial-temporal expressions of Crumbs and Nagie oko and their interdependence in zebrafish central nervous system during early development

A vast number of apicobasal polarity proteins play essential roles in the polarization and morphogenesis of the neuroepithelia. Crumbs (Crb) type I transmembrane cell–cell adhesion proteins are among these proteins. Five crb genes have been identified in zebrafish. However, their expressional and functional differences during early neural development remain to be fully elucidated. Here, we study the spatial-temporal expression patterns and functions of Crb1, Crb2a, and Crb2b in the central nervous system (CNS) during the neurulation period. We show that: 1, the optic vesicle and undifferentiated retinal neuroepithelium only express Crb2a; 2, Crb1 and Crb2a expressions overlap extensively in the undifferentiated neural tube epithelium; 3, Crb2b expression is the weakest of the three and is restricted to the ventral-most regions of the anterior CNS; and 4, Nok and Crb proteins require each other for their apical localization in neuroepithelium. The commencements of Crb1, Crb2a, and Crb2b expressions follow a spatial-temporal spread from anterior to posterior and from ventral to dorsal and lag behind that of adherens junction components, such as ZO-1 and actin bundles. Genetic and morpholino suppression analyses suggest that in regions where these Crb expressions overlap, they are functionally redundant in maintaining apicobasal polarity of the undifferentiated neuroepithelium.     

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis

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Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS

BACKGROUND & AIMS: Both psychological and mucosal changes (increased enterochromaffin [EC] cells and T lymphocytes) have been associated with postinfectious irritable bowel syndrome (PI-IBS). However, previous studies have been underpowered to determine the relative importance of these changes in predicting the development of PI-IBS. Our aim was to prospectively determine the relative importance of both psychological and histologic factors in the development of PI-IBS after Campylobacter infection. METHODS: Questionnaires detailing psychological and bowel symptoms were sent to 1977 patients 3 months after infection. Twenty-eight patients with new-onset PI-IBS, 28 age- and sex-matched patient controls who were asymptomatic after infection, and 34 healthy volunteers underwent rectal biopsy, which was assessed for serotonin-containing EC cells, mast cells, and lamina propria T lymphocytes. RESULTS: PI-IBS, predominantly of the diarrhea-predominant subtype, occurred in 103 of 747 (13.8%) of those infected. EC cell counts per high-power field (hpf) were higher in patients with PI-IBS (35.8 +/- 1.2) compared with patient controls (30.6 +/- 1.9; P = 0.022) and volunteers (29.1 +/- 1.8; P = 0.006). Lamina propria T lymphocytes per hpf were higher in patients with PI-IBS (127.1 +/- 8.7) and patient controls (113.4 +/- 6.2) in contrast to healthy volunteers (97.1 +/- 5.7) (P = 0.006 and P = 0.058, respectively). Anxiety, depression, and fatigue were significantly increased in patients with PI-IBS compared with patient controls. Multivariate analysis indicated that increased EC cell counts and depression were equally important predictors of developing PI-IBS (relative risk, 3.8 and 3.2 for each standard deviation increase in respective values). CONCLUSIONS: Both increased EC cells and depression are important independent predictors of developing PI-IBS.     

Neutrophil chemotactic activity in milk-induced asthma

Four subjects with clinical histories of milk-induced asthma were studied (three allergic to cow's milk; one to soya milk). In each instance, skin prick tests, RAST (IgE and IgG₄), the basophil histamine release, and serum precipitins, using appropriate milk extracts, were negative. After the ingestion of milk all the subjects developed a reproducible and dose-dependent increase in airflow limitation. Three patients (two allergic to cow's milk; one to soya milk) gave a characteristic immediate-type reaction, which was maximal at 30 min after challenge. The fourth individual developed an isolated late-phase response, with maximal airways obstruction 3 hr after ingesting milk. In the three subjects who gave an early reaction, wheezing was accompanied by an elevation in circulating neutrophil chemotactic activity (NCA). This was not observed in the individual with the isolated late reaction. By Sephacryl S-400 gel-filtration chromatography it was shown that NCA of the early reactions eluted with proteins having an estimated molecular weight of 600,000 daltons. The immediate asthmatic response in peak expiratory flow rate and the elevation in NCA were inhibited by the prior oral administration of either disodium cromoglycate (DSCG) or oral beclomethasone dipropionate (BDP). In contrast, DSCG had no effect on airways obstruction in the subject with the isolated late asthmatic response, although inhibition was achieved by BDP.