A5079333509- Liver physiology and pathology
- Liver Diseases and Immunity
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Pancreatic function and diabetes
- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Systemic Lupus Erythematosus Research
- Metabolism and Genetic Disorders
- Biochemical Acid Research Studies
- Celiac Disease Research and Management
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Congenital Anomalies and Fetal Surgery
- Drug Transport and Resistance Mechanisms
- Genetic and Kidney Cyst Diseases
- Tissue Engineering and Regenerative Medicine
- Innovations in Medical Education
- Diabetes and associated disorders
- Muscle Physiology and Disorders
- Electrolyte and hormonal disorders
- interferon and immune responses
- Clinical Nutrition and Gastroenterology
- Macrophage Migration Inhibitory Factor
Royal Derby Hospital
2017
University of Nottingham
2017
University of Birmingham
1995-2015
NIHR Birmingham Liver Biomedical Research Unit
1997-2008
Queen Elizabeth Hospital Birmingham
1991-2005
Queen Elizabeth Hospital
2003
University of Glasgow
1998-2003
LMU Klinikum
2000
Ludwig-Maximilians-Universität München
2000
Birmingham Children's Hospital
1997-1998
Patients with primary biliary cirrhosis develop progressive ductopenia associated the production of antimitochondrial antibodies that react a protein aberrantly expressed on epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest viral association cirrhosis. Here we describe...
Liver involvement in autosomal dominant polycystic kidney disease (ADPKD) is characterized by altered remodeling of the embryonic ductal plate (DP) with presence biliary cysts and aberrant portal vasculature. The genetic defect causing ADPKD has been identified, but mechanisms liver cyst growth remain uncertain. To investigate possible role angiogenic mechanisms, we have studied immunohistochemical expression vascular endothelial factor (VEGF), angiopoietin–1 (Ang-1), angiopoietin-2 (Ang-2)...
In previous studies, intrahepatic human biliary epithelial cells (BEC) were isolated in high purity. However, these demonstrated only limited growth responses. Here we report that BEC proliferate response to hepatocyte factor (hHGF), retain BEC-specific phenotype, and can be serially passaged. showed dose-dependent 0.01-100 ng/ml hHGF. The maximum S-phase labeling index reached 40% with half-maximal stimulation at 1 ng/ml. of from normal primary cirrhotic liver hHGF was similar. Cultures...
Primary biliary cirrhosis (PBC) is a cholestatic disease associated with autoimmune phenomena and alterations in both bicarbonate excretion expression of the carrier AE2. The bile acid ursodeoxycholic (UCDA) currently used treatment liver diseases choice PBC; however, subset PBC patients respond poorly to UDCA monotherapy. In these patients, combination glucocorticoid therapy appears be beneficial. To address mechanism this benefit, we analyzed effects dexamethasone on AE2 gene human cells...
Human intrahepatic biliary epithelial cells were isolated from the livers of patients with primary cirrhosis and normal established in culture. The vitro expression intercellular adhesion molecule-1, HLA class I, II on was studied response to tumour necrosis factor-alpha (0-500 U/ml), interferon-gamma interleukin-1 (0-5 U/ml) by immunohistochemical staining a semiquantitative scoring system validated spectrophotometry previously laser confocal microscopy. non-stimulated molecule-1 higher...
The existence of progenitor (stem) cells in the human liver remains a matter debate. In rodent models hepatocarcinogenesis and injury, oval proliferate periportal regions portal tracts are suggested to derive from stem cell compartment, because they capable differentiating into hepatocytes or biliary epithelial cells. this study, rat marker, OV-6 has been used investigate hypothesis that there present fetal pediatric liver. pattern expression was compared with established adult markers...
Primary biliary cirrhosis (PBC) is a disorder of unknown origin with autoimmune features. Recently, impaired secretion bicarbonate has been shown in patients PBC. Here we have investigated whether bile duct epithelial cells isolated from PBC exhibit defects transepithelial transport by analyzing the activities 2 ion exchangers, Cl − /HCO 3 anion exchanger (AE2) and Na + /H (NHE) cholangiocytes. AE2 NHE were studied basal conditions after stimulation cyclic adenosine monophosphate (cAMP)...
// Stuart Duncan Morton 1, * , Massimiliano Cadamuro 2, Simone Brivio 2 Marta Vismara Tommaso Stecca 3 Marco Massani Nicolò Bassi 3, 4 Alberto Furlanetto 5 Ruth Elizabeth Joplin 6 Annarosa Floreani Luca Fabris 7 Mario Strazzabosco 1 Department of Molecular Medicine, University Padua, Italy Surgery & Translational Milan-Bicocca, Milan, Fourth Division, Treviso Regional Hospital, Treviso, Surgical, Oncological and Gastroenterological Sciences, Pathology Unit, School Immunity Infection,...
Abstract Today's medical students are faced with numerous learning needs. Continuously developing curricula have reduced time for basic science subjects such as anatomy. This study aimed to determine the students' views on relevance of anatomy teaching, anatomical knowledge, and effect these their career choices. A Likert scale questionnaire was distributed second year [response rate 91% ( n = 292/320)]. The same subsequently cohort three years later when they were final 37% 146/392)]....
Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis this still unknown, high titers antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little known about presence AMA bile. In study, we investigated and sera from patients with PBC healthy controls for mitochondrial autoantigens. were detected 17 19 (89.4%) PBC; they specifically directed against pyruvate...
Biliary epithelial cells (cholangiocytes) modulate bile fluidity and alkalinity absorbing and/or secreting fluid electrolytes, particularly HCO 3 − Cl . Mechanisms responsible for transepithelial H + /HCO secretion in human cholangiocytes are largely unknown. Human isolated by enzymatic digestion immunomagnetic purification from normal liver tissue obtained reduced grafts used pediatric transplantation were cultured the presence of hepatocyte growth factor. Maintenance cholangiocyte...
The reason for the close association between primary biliary cirrhosis and appearance of antibodies that recognize E2 component pyruvate dehydrogenase complex is not understood. distribution three subunits was examined in liver lymph nodes patients with cirrhosis, other diseases normal subjects by immunohistochemistry using affinity-purified antibodies. Intensity staining assessed semiquantitatively validated scanning laser confocal microscopy. In tissue, pattern did parallel reported...
Although the control of biliary ductular morphogenesis has received some attention particularly using isolated rat epithelial cell models, regulation human bile duct formation is not well defined. In present study, a 3-dimensional culture model comprising primary cells (BECs) and coculture with hepatocytes, we have sought to define factors involved. We shown that BECs can be expanded on collagen gels in absence growth or serum. When plated high density double gels, established structures...
Since biliary epithelial cells of the middle-sized interlobular bile ducts are targets for lymphocyte-mediated damage in patients with primary cirrhosis (PBC), we have developed a method isolating and maintaining these short-term tissue culture. Intrahepatic were isolated from small segments liver removed at time transplantation. Cells separated collagenase digest by immunomagnetic separation using Dynabeads coupled to monoclonal antibody (HEA 125) specific cell surface antigen. The yield...
Previous studies in which quantitative immunofluorescence was used have shown that certain biliary epithelial cells liver with primary cirrhosis show increased levels of pyruvate dehydrogenase dihydrolipoamide acetyltransferase compared controls. This study designed to determine whether the increase intensity is accounted for by an number mitochondria same cells. A double-antibody staining technique antibodies specific and another mitochondrial inner membrane marker, recognized mouse...