A5041869113- Pancreatic function and diabetes
- Diabetes and associated disorders
- Pancreatic and Hepatic Oncology Research
- Diabetes Management and Research
- Esophageal and GI Pathology
- Gastrointestinal disorders and treatments
- Pancreatitis Pathology and Treatment
- Intestinal Malrotation and Obstruction Disorders
- Metabolism, Diabetes, and Cancer
- Genetics and Neurodevelopmental Disorders
- Diet, Metabolism, and Disease
- Congenital gastrointestinal and neural anomalies
- Abdominal Trauma and Injuries
- Virus-based gene therapy research
- Intestinal and Peritoneal Adhesions
- Congenital heart defects research
- Hemoglobinopathies and Related Disorders
- Diabetes Treatment and Management
- Parasites and Host Interactions
- Pediatric Hepatobiliary Diseases and Treatments
- Tracheal and airway disorders
- Appendicitis Diagnosis and Management
- Viral gastroenteritis research and epidemiology
- Congenital Diaphragmatic Hernia Studies
- Autopsy Techniques and Outcomes
Leeds Teaching Hospitals NHS Trust
2021-2024
Children's Hospital & Medical Center
2022
University of Nebraska Medical Center
2022
Nationwide Children's Hospital
2020-2021
St. Jude Children's Research Hospital
2017-2020
University of Tennessee Health Science Center
2019
Jinnah Sindh Medical University
2019
Le Bonheur Children's Hospital
2019
Hospital Universitario Virgen del Rocío
2019
Children's Hospital of Pittsburgh
2010-2017
Significance Here, we show how, mechanistically, inflammation-recruited macrophages may stimulate beta-cell proliferation in the pancreas, and specifically identify that TGFβ1 EGF, which are secreted by M2 macrophages, induce SMAD7 expression beta cells. not only activates cell cycle activators but also induces nuclear exclusion of inhibitors to promote replication. Our study thus reveals a molecular pathway through enhanced activity
Whether facultative β cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. track neogenesis vivo, we generated transgenic mice that transiently coexpress mTomato and GFP time-sensitive, nonconditional Cre-mediated manner, so insulin-producing cells express under control of insulin promoter, while all other (INSCremTmG mice). Newly differentiated were detected by flow cytometry fluorescence microscopy,...
Protection and restoration of a functional β-cell mass are fundamental strategies for prevention treatment diabetes. Consequently, knowledge signals that determine the is immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play critical role in development tissue specification. Nevertheless, these adult homeostasis not well defined. Here, we ablated TGFβ receptor I II genes mice undergoing two surgical replication models (partial pancreatectomy or...
VEGF-A expression in beta cells is critical for pancreatic development, formation of islet-specific vasculature, and Insulin secretion. However, two key questions remain. First, release from coupled to production cells? Second, how the response by affected metabolic signals? Here, we show that secretion, but not gene transcription, either cultured islets or purified cells, was significantly reduced early on during low glucose conditions. In vivo, a sustained hypoglycemia mice induced with...
Pancreatic β-cell loss and dysfunction are critical components of all types diabetes. Human rodent β-cells able to proliferate, this proliferation is an important defense against the evolution progression Transforming growth factor-β (TGF-β) signaling has been shown affect development, proliferation, function, but thought be only source new in adult. Recently, dedifferentiation contributory mechanism failure. In study, we tie together these two pathways by showing that a network...
BackgroundMany patients with anorectal malformations (ARM) need a bowel management program (BMP) to manage lifelong problems of fecal incontinence or severe constipation. We aimed evaluate the sustainability results in such program.MethodsA single-institution retrospective review was performed children ARM who attended our BMP (2015–2019). Standardized definitions and validated tools were used assess continence (Baylor Continence Scale), constipation (Cleveland Constipation Scoring System),...
Abstract A key question in diabetes research is whether new β-cells can be derived from endogenous, nonendocrine cells. The potential for pancreatic ductal cells to convert into a highly debated issue. To date, it remains unclear what anatomical process would result duct-derived coming exist within preexisting islets. We used whole-mount technique directly visualize the network young wild-type mice, humans, and transgenic mice after partial pancreatectomy. Pancreatic networks, originating...
Glucagon-producing α-cells are the second-most abundant cell type in islet. Whereas make up less than 20% of cells a mature mouse islet, they occupy much larger proportion pancreatic endocrine population during early postnatal period, time when morphological and functional maturation occurs to form adult islets. To determine whether have role islet development, diphtheria toxin-mediated α-cell ablation model was established. Rapid persistent depletion achieved by daily injection toxin for 2...
Adeno-Associated Virus (AAV) has been widely used for in vivo study and preclinical therapy due to its ability mediate long-term transgene expression, lack of pathogenicity low immunogenicity. It found that AAV more than ten serotypes, which each transfect certain types cells the viral infected organ. Current methods purification different serotypes utilize CsCl or Iodixanol ultrahigh speed density gradient centrifugation, is expensive time consuming. We recently developed a simplified...
The pancreatic islets of Langerhans are highly vascularized structures scattered throughout the pancreas that contain a capillary network 5-10 times denser than exocrine pancreas. A simple method for three-dimensional (3D) analysis this intricate intraislet vasculature has been difficult because intrinsic opacity We developed whole-mount imaging technique allows relatively easy visualization islet vasculature. In combination with confocal microscopy and use 3D software, we were able to...
Specific labeling of pancreatic ducts has proven to be quite difficult. Such been highly sought after because the power it would confer studies ductal carcinogenesis, as well source new insulin-producing β-cells. Cre-loxp recombination could, in theory, lineage-tag ducts, but results have conflicting, mainly due low efficiencies. Here, we achieved a high duct efficiency using recombinant adeno-associated virus (rAAV) with duct-specific sox9 promoter infused into mouse common...
Confocal microscopy in combination with commercial software is frequently used to generate three-dimensional images of tissue architecture. Here we report a novel, whole-mount imaging protocol technique that allows detailed adult pancreatic structures. This provides an improved appreciation the anatomical detail structures and relationship between ducts islets. In addition, revealed previously unappreciated high degree hypervascularity.
Glucose-dependent insulinotropic polypeptide (GIP) is a member of structurally related group hormones that also includes glucagon, glucagon-like peptides, and secretin. GIP an incretin, known to modulate glucose-induced insulin secretion. Recent studies have shown glucagon necessary for early insulin-positive differentiation, similar role incretins in regulating embryonic differentiation seems probable. Here we studied the signaling mouse pancreas.The ontogeny ligand receptor pancreas was...
Introduction: Pyloric stenosis is a common cause of vomiting in infancy and usually treated with Ramstedt's pyloromyotomy. In this study we retrospectively reviewed our experience the circumumbilical incision for treatment pyloric particular emphasis on relation between postoperative emesis time to feeds.