Myosin Vb Traffics P-Glycoprotein to the Apical Membrane of Intestinal Epithelial Cells.

Background & Aims: The xenobiotic efflux pump P-glycoprotein is highly expressed on the apical membrane of the gastrointestinal tract, where it regulates the levels of intracellular substrates. P-glycoprotein is altered in disease, but the mechanisms that regulate the levels of P-glycoprotein are still being explored. The molecular motor myosin Vb (Myo5b) traffics diverse cargo to the apical membrane of intestinal epithelial cells.

Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease.

Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes.

Therapy Development for Microvillus Inclusion Disease using Patient-derived Enteroids.

Unlabelled: Microvillus Inclusion Disease (MVID), caused by loss-of-function mutations in the motor protein Myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid-base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes.

Editing Myosin VB Gene to Create Porcine Model of Microvillus Inclusion Disease, With Microvillus-Lined Inclusions and Alterations in Sodium Transporters.

Background & Aims: Microvillus inclusion disease (MVID) is caused by inactivating mutations in the myosin VB gene (MYO5B). MVID is a complex disorder characterized by chronic, watery, life-threatening diarrhea that usually begins in the first hours to days of life. We developed a large animal model of MVID to better understand its pathophysiology.

Loss of MYO5B Leads to Reductions in Na Absorption With Maintenance of CFTR-Dependent Cl Secretion in Enterocytes.

Background & Aims: Inactivating mutations in MYO5B cause microvillus inclusion disease (MVID), but the physiological cause of the diarrhea associated with this disease is unclear. We investigated whether loss of MYO5B results in aberrant expression of apical enterocyte transporters.

Methods: We studied alterations in apical membrane transporters in MYO5B-knockout mice, as well as mice with tamoxifen-inducible, intestine-specific disruption of Myo5b (VilCre;Myo5b mice) or those not given tamoxifen (controls).

Quality indicators for pediatric colonoscopy: results from a multicenter consortium.

Background And Aims: Currently, there are no quality measures specific to children undergoing GI endoscopy. We aimed to determine the baseline quality of pediatric colonoscopy by using the Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative (PEDS-CORI), a central registry.

Methods: We conducted prospective data collection by using a standard computerized report generator and central registry (PEDS-CORI) to examine key quality indicators from 14 pediatric centers between January 2000 and December 2011.

Therapy of caustic ingestion: new treatment considerations.

Purpose Of Review: This review will focus on therapeutic considerations and recent advances in treatment of caustic ingestion injuries.

Recent Findings: A retrospective study suggests that it may be safe to advance the endoscope beyond the first circumferential burn to allow for a more complete assessment of extent of injury. A randomized controlled prospective study suggested that a 3-day course of high-dose methylprednisolone might reduce the occurrence of esophageal stricture formation.

Rab11a regulates syntaxin 3 localization and microvillus assembly in enterocytes.

Rab11a is a key component of the apical recycling endosome that aids in the trafficking of proteins to the luminal surface in polarized epithelial cells. Utilizing conditional Rab11a-knockout specific to intestinal epithelial cells, and human colonic epithelial CaCo2-BBE cells with stable Rab11a knockdown, we examined the molecular and pathological impact of Rab11a deficiency on the establishment of apical cell polarity and microvillus morphogenesis. We demonstrate that loss of Rab11a induced alterations in enterocyte polarity, shortened microvillar length and affected the formation of microvilli along the lateral membranes.

Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease.

Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We have examined the association of mutations in MYO5B and disruption of microvillar assembly and polarity in enterocytes. Stable MYO5B knockdown (MYO5B-KD) in CaCo2-BBE cells elicited loss of microvilli, alterations in junctional claudins, and disruption of apical and basolateral trafficking; however, no microvillus inclusions were observed in MYO5B-KD cells.

Navajo microvillous inclusion disease is due to a mutation in MYO5B.

Microvillous Inclusion Disease (MID) is a rare, autosomal recessive gastrointestinal disease of increased frequency among the Navajos. Previous work has shown a deficiency of RAB8 in one Japanese patient, while homozygous mutations in MYO5B were found in 7 of 10 mostly Middle Eastern families. We have identified a shared homozygous mutation in MYO5B in seven affected Navajos with the expected heterozygosity in five parents.

Prevalence of endoscopic findings of erosive esophagitis in children: a population-based study.

Purpose: Symptoms of gastroesophageal reflux disease (GERD) occur in 2% to 7% of children. The manifestations of GERD can be limited to symptoms (eg, heartburn, regurgitation) or can be more complicated, such as erosive esophagitis, esophageal strictures, or Barrett esophagus. The prevalence of such GERD complications in children is unknown.

The prevalence of suspected Barrett's esophagus in children and adolescents: a multicenter endoscopic study.

Background: The prevalence of Barrett's esophagus (BE) in young individuals is unclear.

Objective: To estimate the prevalence of suspected BE in children and adolescent patients undergoing endoscopy.

Design: A retrospective cross-sectional study.