21 results on '"Shub MD"'
Search Results
2. Myosin Vb Traffics P-glycoprotein to the Apical Membrane of Intestinal Epithelial Cells.
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Dooley SA, Kolobova E, Burman A, Kaji I, Digrazia JR, Stubler R, Goldstein A, Packirisamy C, Coutts AW, Saqui-Salces M, Gao N, Engevik MA, Shub MD, Goldenring JR, and Engevik AC
- Abstract
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 which 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. We hypothesized that Myo5b was responsible for delivery of P-glycoprotein to the apical membrane of enterocytes., Methods: We used multiple murine models that lack functional Myo5b or the myosin binding partner Rab11a to analyze P-glycoprotein localization. Pig and human tissue were analyzed to determine P-glycoprotein localization in the setting of MYO5B mutations. Intestinal organoids were used to examine P-glycoprotein trafficking and to assay P-glycoprotein function when MYO5 is inhibited., Results: In mice lacking Myo5b or the binding partner Rab11a, P-glycoprotein was improperly trafficked and had decreased presence in the brush border of enterocytes. Immunostaining of a pig model lacking functional Myo5b and human biopsies from a patient with an inactivating mutation in Myo5b also showed altered localization of intestinal P-glycoprotein. Human intestinal organoids expressing the motorless MYO5B tail domain had co-localization with P-glycoprotein, confirming that P-glycoprotein was trafficked by MYO5B in human enterocytes. Inhibition of MYO5 in human intestinal cell lines and organoids resulted in decreased P-glycoprotein capacity. Additionally, inhibition of MYO5 in human colon cancer cells diminished P-glycoprotein activity and increased cell death in response to a chemotherapeutic drug., Conclusions: Collectively, these data demonstrate that Myo5b is necessary for the apical delivery of P-glycoprotein., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2024
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3. Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease.
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Kalashyan M, Raghunathan K, Oller H, Bayer MT, Jimenez L, Roland JT, Kolobova E, Hagen SJ, Goldsmith JD, Shub MD, Goldenring JR, Kaji I, and Thiagarajah JR
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- Humans, Microvilli genetics, Myosin Heavy Chains genetics, Enterocytes metabolism, Myosin Type V genetics, Malabsorption Syndromes genetics, Malabsorption Syndromes therapy, Malabsorption Syndromes metabolism, Mucolipidoses genetics, Mucolipidoses therapy, Mucolipidoses metabolism
- Abstract
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. Multiplex immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na+/H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel-blocking antidiarrheal drug crofelemer dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. γ-Secretase inhibition with DAPT recovered apical brush border structure and functional Na+/H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum/glucocorticoid-regulated kinase 2 (SGK2) and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID.
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- 2023
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4. Therapy Development for Microvillus Inclusion Disease using Patient-derived Enteroids.
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Kalashyan M, Raghunathan K, Oller H, Theres MB, Jimenez L, Roland JT, Kolobova E, Hagen SJ, Goldsmith JD, Shub MD, Goldenring JR, Kaji I, and Thiagarajah JR
- Abstract
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. Multiplex Immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na
+ /H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel-blocking anti-diarrheal drug, Crofelemer, dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. Inhibition of Notch signaling with the γ-secretase inhibitor, DAPT, recovered apical brush border structure and functional Na+ /H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum- and glucocorticoid-induced protein kinase 2 (SGK2), and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID., Conflict-Of-Interest Statement: The authors have declared that no conflict of interest exists.- Published
- 2023
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5. Editing Myosin VB Gene to Create Porcine Model of Microvillus Inclusion Disease, With Microvillus-Lined Inclusions and Alterations in Sodium Transporters.
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Engevik AC, Coutts AW, Kaji I, Rodriguez P, Ongaratto F, Saqui-Salces M, Medida RL, Meyer AR, Kolobova E, Engevik MA, Williams JA, Shub MD, Carlson DF, Melkamu T, and Goldenring JR
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- Animals, Animals, Genetically Modified, Cells, Cultured, Coculture Techniques, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Disease Models, Animal, Duodenum pathology, Genetic Predisposition to Disease, Humans, Intestinal Mucosa pathology, Malabsorption Syndromes metabolism, Malabsorption Syndromes pathology, Microvilli genetics, Microvilli metabolism, Mucolipidoses metabolism, Mucolipidoses pathology, Mutation, Missense, Phenotype, Sodium metabolism, Sodium-Glucose Transporter 1 genetics, Sodium-Hydrogen Exchanger 3 genetics, Sus scrofa, Duodenum metabolism, Gene Editing, Intestinal Mucosa metabolism, Malabsorption Syndromes genetics, Microvilli pathology, Mucolipidoses genetics, Myosin Heavy Chains genetics, Myosin Type V genetics, Sodium-Glucose Transporter 1 metabolism, Sodium-Hydrogen Exchanger 3 metabolism
- Abstract
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., Methods: Pigs were cloned by transfer of chromatin from swine primary fetal fibroblasts, which were edited with TALENs and single-strand oligonucleotide to introduce a P663-L663 substitution in the endogenous swine MYO5B (corresponding to the P660L mutation in human MYO5B, associated with MVID) to fertilized oocytes. We analyzed duodenal tissues from patients with MVID (with the MYO5B P660L mutation) and without (controls), and from pigs using immunohistochemistry. Enteroids were generated from pigs with MYO5B(P663L) and without the substitution (control pigs)., Results: Duodenal tissues from patients with MVID lacked MYO5B at the base of the apical membrane of intestinal cells; instead MYO5B was intracellular. Intestinal tissues and derived enteroids from MYO5B(P663L) piglets had reduced apical levels and diffuse subapical levels of sodium hydrogen exchanger 3 and SGLT1, which regulate transport of sodium, glucose, and water, compared with tissues from control piglets. However, intestinal tissues and derived enteroids from MYO5B(P663L) piglets maintained CFTR on apical membranes, like tissues from control pigs. Liver tissues from MYO5B(P663L) piglets had alterations in bile salt export pump, a transporter that facilitates bile flow, which is normally expressed in the bile canaliculi in the liver., Conclusions: We developed a large animal model of MVID that has many features of the human disease. Studies of this model could provide information about the functions of MYO5B and MVID pathogenesis, and might lead to new treatments., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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6. Loss of MYO5B Leads to Reductions in Na + Absorption With Maintenance of CFTR-Dependent Cl - Secretion in Enterocytes.
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Engevik AC, Kaji I, Engevik MA, Meyer AR, Weis VG, Goldstein A, Hess MW, Müller T, Koepsell H, Dudeja PK, Tyska M, Huber LA, Shub MD, Ameen N, and Goldenring JR
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- Animals, Aquaporins metabolism, Duodenum metabolism, Duodenum pathology, Gene Silencing, Humans, Intestinal Mucosa, Intestines cytology, Intestines pathology, Malabsorption Syndromes pathology, Mice, Mice, Knockout, Microvilli genetics, Mucolipidoses pathology, Protein Transport, Sodium-Glucose Transporter 1 metabolism, Sodium-Hydrogen Exchanger 3 metabolism, Sucrase-Isomaltase Complex metabolism, Tamoxifen administration & dosage, Chlorides metabolism, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Enterocytes metabolism, Malabsorption Syndromes genetics, Microvilli pathology, Mucolipidoses genetics, Myosin Type V genetics, Sodium-Hydrogen Exchangers metabolism
- Abstract
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
ERT2 ;Myo5bflox/flox mice) or those not given tamoxifen (controls). Intestinal tissues were collected from mice and analyzed by immunostaining, immunoelectron microscopy, or cultured enteroids were derived. Functions of brush border transporters in intestinal mucosa were measured in Ussing chambers. We obtained duodenal biopsy specimens from individuals with MVID and individuals without MVID (controls) and compared transporter distribution by immunocytochemistry., Results: Compared to intestinal tissues from littermate controls, intestinal tissues from MYO5B-knockout mice had decreased apical localization of SLC9A3 (also called NHE3), SLC5A1 (also called SGLT1), aquaporin (AQP) 7, and sucrase isomaltase, and subapical localization of intestinal alkaline phosphatase and CDC42. However, CFTR was present on apical membranes of enterocytes from MYO5B knockout and control mice. Intestinal biopsies from patients with MVID had subapical localization of NHE3, SGLT1, and AQP7, but maintained apical CFTR. After tamoxifen administration, VilCreERT2 ;Myo5bflox/flox mice lost apical NHE3, SGLT1, DRA, and AQP7, similar to germline MYO5B knockout mice. Intestinal tissues from VilCreERT2 ;Myo5bflox/flox mice had increased CFTR in crypts and CFTR localized to the apical membranes of enterocytes. Intestinal mucosa from VilCreERT2 ;Myo5bflox/flox mice given tamoxifen did not have an intestinal barrier defect, based on Ussing chamber analysis, but did have decreased SGLT1 activity and increased CFTR activity., Conclusions: Although trafficking of many apical transporters is regulated by MYO5B, trafficking of CFTR is largely independent of MYO5B. Decreased apical localization of NHE3, SGLT1, DRA, and AQP7 might be responsible for dysfunctional water absorption in enterocytes of patients with MVID. Maintenance of apical CFTR might exacerbate water loss by active secretion of chloride into the intestinal lumen., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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7. Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease.
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Schlegel C, Weis VG, Knowles BC, Lapierre LA, Martin MG, Dickman P, Goldenring JR, and Shub MD
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- Child, Female, Genetic Predisposition to Disease, Humans, Indians, North American, Infant, Infant, Newborn, Kidney, Malabsorption Syndromes genetics, Male, Microvilli genetics, Microvilli metabolism, Mucolipidoses genetics, Mutation, Myosin Heavy Chains genetics, Myosin Heavy Chains metabolism, Myosin Type V genetics, Myosin Type V metabolism, Pancreas, Stomach, Cell Membrane physiology, Malabsorption Syndromes metabolism, Microvilli pathology, Mucolipidoses metabolism
- Abstract
Objectives: Microvillus inclusion disease (MVID) is a severe form of neonatal diarrhea, caused mainly by mutations in MYO5B. Inactivating mutations in MYO5B causes depolarization of enterocytes in the small intestine, which gives rise to chronic, unremitting secretory diarrhea. While the pathology of the small intestine in MVID patients is well described, little is known about extraintestinal effects of MYO5B mutation., Methods: We examined stomach, liver, pancreas, colon, and kidney in Navajo MVID patients, who share a single homozygous MYO5B-P660L (1979C>T p.Pro660Leu, exon 16). Sections were stained for markers of the apical membrane to assess polarized trafficking., Results: Navajo MVID patients showed notable changes in H/K-ATPase-containing tubulovesicle structure in the stomach parietal cells. Colonic mucosa was morphologically normal, but did show losses in apical ezrin and Syntaxin 3. Hepatocytes in the MVID patients displayed aberrant canalicular expression of the essential transporters MRP2 and BSEP. The pancreas showed small fragmented islets and a decrease in apical ezrin in pancreatic ducts. Kidney showed normal primary cilia., Conclusions: These findings indicate that the effects of the P660L mutation in MYO5B in Navajo MVID patients are not limited to the small intestine, but that certain tissues may be able to compensate functionally for alterations in apical trafficking.
- Published
- 2018
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8. Quality indicators for pediatric colonoscopy: results from a multicenter consortium.
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Thakkar K, Holub JL, Gilger MA, Shub MD, McOmber M, Tsou M, and Fishman DS
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- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Intubation, Gastrointestinal, Male, Prospective Studies, Young Adult, Colonoscopy standards, Documentation standards, Quality Indicators, Health Care, Registries
- Abstract
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. Specific quality indicators, including bowel preparation, ileal intubation rate, documentation of American Society of Anesthesiologists Physical Status Classification System (ASA) class, and procedure time, were compared during the study period., Results: We analyzed 21,807 colonoscopy procedures performed in patients with a mean age of 11.5 ± 4.8 years. Of the 21,807 reports received during the study period, 56% did not include bowel preparation quality, and 12.7% did not include ASA classification. When bowel preparation was reported, the quality was described as excellent, good, or fair in 90.3%. The overall ileal intubation rate was 69.4%, and 15.6% reported cecal intubation only, calculated to be 85% cecum or ileum intubation. Thus, 15% of colonoscopy procedures did not report reaching the cecum or ileum. When excluding the proportion of procedures not intended to reach the ileum (31.5%), the overall ileal intubation rate increased to 84.0%. The rate of ileum examination varied from 85% to 95%, depending on procedure indication., Conclusions: Colonoscopy reports from our central registry revealed significant variations and inconsistent documentation in pediatric colonoscopy. Our study identifies areas for quality improvement and highlights the need for developing accepted quality measures specific to pediatric endoscopy., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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9. Therapy of caustic ingestion: new treatment considerations.
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Shub MD
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- Accidents, Burns, Chemical diagnosis, Burns, Chemical prevention & control, Child, Child, Preschool, Dilatation methods, Esophageal Stenosis chemically induced, Humans, Injury Severity Score, Practice Guidelines as Topic, Randomized Controlled Trials as Topic, Retrospective Studies, Stents, Treatment Outcome, Alkylating Agents administration & dosage, Burns, Chemical therapy, Caustics adverse effects, Dilatation instrumentation, Esophageal Stenosis therapy, Mitomycin administration & dosage
- Abstract
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. Balloon dilatation has been shown to be as effective as other bougienage techniques with lower risk of perforations. Recent studies indicate that esophageal dilatation can be safely performed as early as 5-15 days after initial ingestion and may decrease risk for long-term stricture formation. The use of adjunctive treatment, such as topical mitomycin C and esophageal stents, shows promise in reducing the reoccurrence of stricture formation after dilatation., Summary: Caustic ingestion remains a significant problem in children, despite continued efforts to educate the public about ways to avoid this preventable accident. Because there are few good quality therapeutic trials in children, many of the current recommendations regarding treatment are based on expert opinion. Large, prospective, multicenter, controlled treatment trials are needed to identify the best protocols to prevent serious complications.
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- 2015
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10. Rab11a regulates syntaxin 3 localization and microvillus assembly in enterocytes.
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Knowles BC, Weis VG, Yu S, Roland JT, Williams JA, Alvarado GS, Lapierre LA, Shub MD, Gao N, and Goldenring JR
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- Animals, Caco-2 Cells, Cell Polarity, Endosomes metabolism, HEK293 Cells, Humans, Mice, Mice, Knockout, Protein Transport, Enterocytes ultrastructure, Microvilli metabolism, Qa-SNARE Proteins metabolism, rab GTP-Binding Proteins metabolism
- Abstract
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. Rab11a deficiency in enterocytes altered the apical localization of syntaxin 3. These data affirm the role of Rab11a in apical membrane trafficking and the maintenance of apical microvilli in enterocytes., (© 2015. Published by The Company of Biologists Ltd.)
- Published
- 2015
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11. Diabetes mellitus in microvillus inclusion disease.
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Oatman OJ, Djedjos CS, Olson ML, and Shub MD
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- Blood Glucose analysis, Child, Diabetes Complications, Diabetes Mellitus drug therapy, Glycosuria, Humans, Insulin administration & dosage, Insulin blood, Malabsorption Syndromes therapy, Male, Mucolipidoses therapy, Parenteral Nutrition, Total, Diabetes Mellitus diagnosis, Malabsorption Syndromes complications, Microvilli pathology, Mucolipidoses complications
- Published
- 2014
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12. Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease.
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Knowles BC, Roland JT, Krishnan M, Tyska MJ, Lapierre LA, Dickman PS, Goldenring JR, and Shub MD
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- Caco-2 Cells, Enterocytes metabolism, Enterocytes pathology, Gene Knockdown Techniques, Humans, Indians, North American genetics, Infant, Malabsorption Syndromes pathology, Mucolipidoses pathology, Mutation, Myosin Heavy Chains antagonists & inhibitors, Myosin Type V antagonists & inhibitors, RNA, Small Interfering genetics, Malabsorption Syndromes etiology, Malabsorption Syndromes metabolism, Microvilli metabolism, Microvilli pathology, Mucolipidoses etiology, Mucolipidoses metabolism, Myosin Heavy Chains genetics, Myosin Heavy Chains metabolism, Myosin Type V genetics, Myosin Type V metabolism, rab GTP-Binding Proteins metabolism
- Abstract
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. Expression of WT MYO5B in MYO5B-KD cells restored microvilli; however, expression of MYO5B-P660L, a MVID-associated mutation found within Navajo populations, did not rescue the MYO5B-KD phenotype but induced formation of microvillus inclusions. Microvilli establishment required interaction between RAB8A and MYO5B, while loss of the interaction between RAB11A and MYO5B induced microvillus inclusions. Using surface biotinylation and dual immunofluorescence staining in MYO5B-KD cells expressing mutant forms of MYO5B, we observed that early microvillus inclusions were positive for the sorting marker SNX18 and derived from apical membrane internalization. In patients with MVID, MYO5B-P660L results in global changes in polarity at the villus tips that could account for deficits in apical absorption, loss of microvilli, aberrant junctions, and losses in transcellular ion transport pathways, likely leading to the MVID clinical phenotype of neonatal secretory diarrhea.
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- 2014
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13. Navajo microvillous inclusion disease is due to a mutation in MYO5B.
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Erickson RP, Larson-Thomé K, Valenzuela RK, Whitaker SE, and Shub MD
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- DNA Mutational Analysis, Electrophoresis, Humans, Polymerase Chain Reaction, Indians, North American ethnology, Indians, North American genetics, Malabsorption Syndromes ethnology, Malabsorption Syndromes genetics, Mutation genetics, Myosin Heavy Chains genetics, Myosin Type V genetics
- Abstract
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. We have developed a simple restriction enzyme based assay that allows for rapid screening for this mutation., (Copyright (c) 2008 Wiley-Liss, Inc.)
- Published
- 2008
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14. The prevalence of suspected Barrett's esophagus in children and adolescents: a multicenter endoscopic study.
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El-Serag HB, Gilger MA, Shub MD, Richardson P, and Bancroft J
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- Adolescent, Adult, Age Factors, Analysis of Variance, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Endoscopy, Gastrointestinal, Esophagitis diagnosis, Esophagitis epidemiology, Hernia, Hiatal diagnosis, Hernia, Hiatal epidemiology, Humans, Infant, Intestinal Polyps diagnosis, Intestinal Polyps epidemiology, Logistic Models, Metaplasia diagnosis, Metaplasia epidemiology, Peptic Ulcer diagnosis, Peptic Ulcer epidemiology, Prevalence, Research Design, Retrospective Studies, Risk Factors, United States epidemiology, Barrett Esophagus diagnosis, Barrett Esophagus epidemiology, Esophagoscopy
- Abstract
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., Setting: Prospectively collected data in the Pediatric Clinical Outcomes Research Initiative (PEDS-CORI)., Patients: We identified patients younger than 20 years of age with suspected BE in the PEDS-CORI between 1999 and 2002; the corresponding histopathologic records were examined., Main Outcome Measurements: We analyzed the distribution of demographic and endoscopic risk factors for BE between cases and non-cases with and without suspected BE in bivariate and multivariable analyses., Results: We identified a total of 6731 patients who underwent upper endoscopy in 12 pediatric facilities. Only 17 patients had suspected BE (prevalence, 2.5 per 1000). Intestinal metaplasia was reported in only 9 of these patients (53%). Patients with suspected BE were older than patients without BE (median 14.7 vs 10.1 years; P = .011). Hiatus hernia was more commonly recorded in patients with suspected BE (11.8% vs 2.2%; P = .008). In a logistic regression model, both older age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02-1.35) and hiatus hernia (OR 4.62, 95% CI 1.03-20.66) were independently associated with suspected BE., Conclusions: Endoscopically suspected BE is rare (<0.25%) in children and adolescents. Older age and the presence of hiatus hernia are possible risk factors for BE in this group., Limitations: Lack of standardization for identifying and recording endoscopic landmarks.
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- 2006
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15. A cluster of microvillous inclusion disease in the Navajo population.
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Pohl JF, Shub MD, Trevelline EE, Ingebo K, Silber G, Rayhorn N, Holve S, and Hu D
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- Arizona, Birth Weight, Cytomegalovirus Infections genetics, Cytomegalovirus Infections physiopathology, Female, Gestational Age, Humans, Infant, Newborn, Male, Microvilli pathology, Phenotype, Cytomegalovirus Infections ethnology, Indians, North American genetics
- Abstract
We report 4 unrelated patients with characteristic microscopic findings of microvillous inclusion disease (MID) with early-onset phenotype. All 4 patients came from the Navajo reservation in northern Arizona. A literature search revealed a fifth unrelated Navajo child with MID. The unusually high incidence in this population indicates that a founder effect might be responsible for an increased frequency of this rare genetic disorder in the Navajo. It is recommended that all Navajo infants presenting with severe diarrhea during early infancy undergo investigation for MID.
- Published
- 1999
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16. Sedation in children: adequacy of two-hour fasting.
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Ingebo KR, Rayhorn NJ, Hecht RM, Shelton MT, Silber GH, and Shub MD
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- Adolescent, Anesthesia, General, Body Weight, Child, Child, Preschool, Gastrointestinal Contents chemistry, Gastroscopy, Humans, Hydrogen-Ion Concentration, Hypnotics and Sedatives administration & dosage, Infant, Pneumonia, Aspiration etiology, Risk Factors, Suction, Time Factors, Fasting, Preanesthetic Medication, Preoperative Care
- Abstract
Objectives: (1) To investigate the relationship between the duration of time that children fasted before a procedure and their gastric volume and pH at the time of the procedure. (2) To compare the variables of gastric pH and volume with historical standards., Methods: We performed 285 gastroscopies for children aged 0.1 to 18.6 years (mean, 7.5 +/- 5.3) between October 1991 and January 1995. Duration of fasting was 0.5 to 24 hours (mean, 6.7 +/- 5.3) after ingestion of clear liquids. Immediately after intravenously administered sedation, the gastric contents were removed endoscopically with suction and direct visualization to ensure complete evacuation. The volume and pH of the gastric contents were measured and analyzed in comparison with the duration of fasting. The values obtained were also compared with historical standards thought to minimize the risk of aspiration pneumonia: gastric volume 0.4 ml or less per kilogram of body weight and pH of 2.5 or greater., Results: There was no significant correlation between duration of fasting and either gastric volume divided by body weight (mean, 0.68 +/- 1.31 ml/kg; range, 0 to 15.23 ml/kg) or pH (mean, 2.03 +/- 1.40; range, 1 to 8). There was less no significant difference in the percentage of children with gastric volume of 0.4 ml/kg or less or with pH of 2.5 or greater between the groups with the following fasting times: 30 minutes to 3 hours, more than 3 hours to 8 hours, and more than 8 hours., Conclusions: On the basis of the data in this study and a review of the literature, we concluded that (1) fasting longer than 2 hours after ingesting clear liquids does not significantly change gastric volume or pH, (2) there is no advantage in requiring children to fast for longer than 2 hours after clear liquid ingestion before sedation or anesthesia for any procedure, and (3) fewer than half of pediatric patients actually achieve the "desirable" values of a gastric volume of 0.4 ml/kg or less and a pH value of 2.5 pH units or more, regardless of fast duration, even though these values are presented in the literature as a goal to minimize the risk of aspiration pneumonia.
- Published
- 1997
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17. Gastrospirillum hominis gastritis in a child with celiac sprue.
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Drewitz DJ, Shub MD, and Ramirez FC
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- Bacterial Infections diagnosis, Bacterial Infections drug therapy, Biopsy, Female, Gastritis diagnosis, Gastritis drug therapy, Humans, Infant, Bacterial Infections complications, Celiac Disease complications, Gastritis microbiology, Helicobacter heilmannii
- Published
- 1997
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18. Esophagitis: a frequent consequence of gastroesophageal reflux in infancy.
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Shub MD, Ulshen MH, Hargrove CB, Siegal GP, Groben PA, and Askin FB
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- Biopsy, Endoscopy, Eosinophils pathology, Esophagitis, Peptic diagnosis, Humans, Infant, Neutrophils pathology, Esophagitis, Peptic pathology, Esophagus pathology
- Abstract
A control group of infants was evaluated to determine criteria for the diagnosis of histologic esophagitis. Based on our observations, histologic esophagitis was defined as four or more intraepithelial neutrophils or one eosinophil per high power field or both. Esophageal biopsy specimens from 33 consecutive infants younger than 2 years who had been examined for clinically significant gastroesophageal reflux (GER) were reviewed for histologic esophagitis. Endoscopy had been performed in each patient, and 4.1 +/- 1.1 (mean +/- SD) biopsy specimens had been obtained above the distal 20% of the esophagus. Twenty (61%) infants had histologic esophagitis, including 15 with intraepithelial eosinophils alone, one with intraepithelial neutrophils alone, and four with both. Older infants (7 to 24 months) with histologic esophagitis were more likely to have moderate to severe inflammation than were infants younger than 7 months of age (P = 0.01). Endoscopic evidence for gross esophagitis was found in six (18%) infants; of these, five had abnormal biopsies, including four with moderate to severe inflammation. Among the 27 infants with a grossly normal esophagus, 14 (52%) had histologic esophagitis, including nine (33%) with moderate to severe inflammation. We conclude that in infants with clinically significant GER: (1) esophagitis is common, (2) histologic esophagitis frequently occurs in the absence of gross endoscopic findings, (3) the likelihood of moderate to severe inflammation increases after 6 months of age, and (4) intraepithelial eosinophils are a sensitive marker for acute inflammation in association with GER.
- Published
- 1985
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19. Age-related changes in chemical composition and physical properties of mucus glycoproteins from rat small intestine.
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Shub MD, Pang KY, Swann DA, and Walker WA
- Subjects
- Amino Acids analysis, Animals, Carbohydrates analysis, Centrifugation, Density Gradient, Chromatography, Gel, Electrophoresis, Polyacrylamide Gel, Female, Intestinal Mucosa analysis, Rats, Rats, Inbred Strains, Aging, Glycoproteins isolation & purification, Intestine, Small analysis, Mucus analysis
- Abstract
Mucus glycoproteins from newborn and adult rat small intestine were radiolabelled in vivo with Na2 35SO4 and isolated from mucosal homogenates by using Sepharose 4B column chromatography followed by CsCl-density-gradient centrifugation. Non-covalently bound proteins, lipids and nucleic acids were not detected in the purified glycoproteins. Amino acid, carbohydrate and sulphate compositions were similar to chemical compositions reported for other intestinal mucus glycoproteins, as were sedimentation properties. There were, however, important differences in the chemical and physical characteristics of the mucus glycoproteins from newborn and adult animals. The buoyant density in CsCl was higher for the glycoproteins from newborn rats (1.55 g/ml versus 1.47 g/ml). On sodium dodecyl sulphate/polyacrylamide/agarose-gel electrophoresis, the glycoprotein from newborn rats had a greater mobility than the adult-rat sample. Although both preparations had similar general amino acid compositions, variations were observed for individual amino acids. The total protein content was greater in the glycoprotein from newborn animals (27%, w/w, versus 18%, w/w). The molar ratio of carbohydrate to protein was less in the newborn, primarily owing to a decreased fucose and N-acetylgalactosamine content. Comparison of the molar ratio of fucose and sialic acid to galactose for both glycoproteins demonstrated a reciprocal relationship similar to that described by Dische [(1963) Ann. N.Y. Acad. Sci. 106, 259-270]. The sulphate content was greater in the glycoprotein from newborn rats (5.5%, w/w, versus 0.9%, w/w). Both had similar sedimentation coefficients in a dissociative solvent. These results suggest an age-related difference in the types of mucus glycoproteins synthesized by small intestine.
- Published
- 1983
- Full Text
- View/download PDF
20. Gastroesophageal reflux and esophagitis in infants and children.
- Author
-
Groben PA, Siegal GP, Shub MD, Ulshen MH, and Askin FB
- Subjects
- Adult, Age Factors, Barrett Esophagus pathology, Child, Preschool, Diagnosis, Differential, Eosinophils, Esophagus pathology, Female, Humans, Hyperplasia, Infant, Neutrophils, Esophagitis diagnosis, Esophagitis pathology, Esophagitis therapy, Gastroesophageal Reflux diagnosis, Gastroesophageal Reflux pathology, Gastroesophageal Reflux therapy
- Published
- 1987
21. Upper gastrointestinal endoscopy in infants: diagnostic usefulness and safety.
- Author
-
Hargrove CB, Ulshen MH, and Shub MD
- Subjects
- Anesthesia, General, Bradycardia etiology, Child, Preschool, Duodenoscopy, Esophagitis, Peptic diagnosis, Esophagitis, Peptic etiology, Esophagoscopy, Evaluation Studies as Topic, Gastroesophageal Reflux diagnosis, Gastroscopy, Humans, Hypnotics and Sedatives therapeutic use, Infant, Infant, Newborn, Premedication, Endoscopy adverse effects, Endoscopy methods, Gastrointestinal Diseases diagnosis
- Abstract
Although fiberoptic, upper gastrointestinal (UGI) endoscopy has become an accepted diagnostic technique in the older child and adult, concerns about safety have limited the use of this procedure in infants. A 1-year experience with 49 upper gastrointestinal endoscopies in infants less than 25 months of age is reported. There were varied indications for the procedures, including upper gastrointestinal hemorrhage and obstruction, but evaluation for esophagitis secondary to gastroesophageal reflux was most common. Procedures were performed without sedation in 45% of all infants studied, including 87% of infants less than 3 months of age; procedures were well tolerated. General anesthesia was used on only three occasions. A thorough examination was always possible, and biopsies were taken whenever indicated. Only one complication, transient bradycardia, occurred in a critically ill infant. This experience demonstrates that upper gastrointestinal endoscopy is a safe and effective diagnostic aid in infants, and it can often be performed with little or no sedation.
- Published
- 1984
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