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Ostrander, Gary K. - One of the best experts on this subject based on the ideXlab platform.
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A novel population health approach: Using fish retinoblastoma gene profiles as a surrogate for humans.
'Elsevier BV', 2009Co-Authors: Rotchell, Jeanette M.., Lyons, Brett P.., Stentiford, Grant D.., Du Corbier, Frances A., Liddle, Andrew R., Ostrander, Gary K.Abstract:Retinoblastoma, a tumor suppressor gene, is frequently mutated in diverse types of human tumors. We have previously shown that two types of fish tumor, eye and Liver, also possess mutant Rb genes. Our aim is to determine if the Rb allele status is linked to environmentally-induced cancer and whether this information in fish can be used to predict future phenotype. This is a proof-of-concept investigation to elucidate if fish may act as surrogates in assessing pollution-induced tumor incidence and inform regulatory authorities of potential long-term population health consequences. Marine flatfish, Limanda limanda, that display either normal Liver histopathology. Liver Adenoma or Liver hepatocellular carcinoma were analysed for the presence of Rb gene alterations. Several Rb alterations were detected in the fish displaying Adenoma and carcinoma, and not in the surrounding normal tissue from the same individuals. The profile is similar to that reported in humans in that they spread across the gene, particularly exons 8-23, and a functionally important region of the protein. This Rb allele data was then used to build statistical classifier sets, linking Rb status with tumor pathology. Further flatfish caught from coastal-water areas of differing contaminant burden around the UK were subsequently analysed for the presence of Rb alterations. Using novel pattern matching statistics of the classifier sets compared with the coastal samples, the coastal fish were considered more similar to the characterised disease phenotype than the normal phenotype. Preliminary data suggests that using a statistical approach, based on classifying sets of histopathologically-defined tumor states, makes it possible to predict the phenotype of wild fish based on the status of the Rb allele. Since the Rb gene is orthologous, fish populations could act as surrogates for human populations in an eco-epidemiological investigation of the combined roles of genetics and environmental exposures in the tumorigenesis process
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A novel population health approach: using fish retinoblastoma gene profiles as a surrogate for humans
'Elsevier BV', 2008Co-Authors: Rotchell, Jeanette M.., Lyons, Brett P.., Stentiford, Grant D.., Du Corbier, Frances A., Liddle, Andrew R., Ostrander, Gary K.Abstract:Retinoblastoma, a tumor suppressor gene, is frequently mutated in diverse types of human tumors. We have previously shown that two types of fish tumor, eye and Liver, also possess mutant Rb genes. Our aim is to determine if the Rb allele status is linked to environmentally-induced cancer and whether this information in fish can be used to predict future phenotype. This is a proof-of-concept investigation to elucidate if fish may act as surrogates in assessing pollution-induced tumor incidence and inform regulatory authorities of potential long-term population health consequences. Marine flatfish, Limanda limanda, that display either normal Liver histopathology. Liver Adenoma or Liver hepatocellular carcinoma were analysed for the presence of Rb gene alterations. Several Rb alterations were detected in the fish displaying Adenoma and carcinoma, and not in the surrounding normal tissue from the same individuals. The profile is similar to that reported in humans in that they spread across the gene, particularly exons 8-23, and a functionally important region of the protein. This Rb allele data was then used to build statistical classifier sets, linking Rb status with tumor pathology. Further flatfish caught from coastal-water areas of differing contaminant burden around the UK were subsequently analysed for the presence of Rb alterations. Using novel pattern matching statistics of the classifier sets compared with the coastal samples, the coastal fish were considered more similar to the characterised disease phenotype than the normal phenotype. Preliminary data suggests that using a statistical approach, based on classifying sets of histopathologically-defined tumor states, makes it possible to predict the phenotype of wild fish based on the status of the Rb allele. Since the Rb gene is orthologous, fish populations could act as surrogates for human populations in an eco-epidemiological investigation of the combined roles of genetics and environmental exposures in the tumorigenesis process. (C) 2008 Elsevier Inc. All rights reserved
Priya S Kishnani - One of the best experts on this subject based on the ideXlab platform.
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variability of disease spectrum in children with Liver phosphorylase kinase deficiency caused by mutations in the phkg2 gene
Molecular Genetics and Metabolism, 2014Co-Authors: Deeksha Bali, Jennifer L Goldstein, Catherine Rehder, Stephanie Austin, Keri Fredrickson, Anne Boney, David A Weinstein, Richard E Lutz, Avihu Boneh, Priya S KishnaniAbstract:Liver phosphorylase b kinase (PhK) deficiency (glycogen storage disease type IX), one of the most common causes of glycogen storage disease, is caused by mutations in the PHKA2, PHKB, and PHKG2 genes. Presenting symptoms include hepatomegaly, ketotic hypoglycemia, and growth delay. Clinical severity varies widely. Autosomal recessive mutations in the PHKG2 gene, which cause about 10-15% of cases, have been associated with severe symptoms including increased risk of Liver cirrhosis in childhood. We have summarized the molecular, biochemical, and clinical findings in five patients, age 5-16 years, diagnosed with Liver PhK deficiency caused by PHKG2 gene mutations. We have identified five novel and two previously reported mutations in the PHKG2 gene in these five patients. Clinical severity was variable among these patients. Histopathological studies were performed for four of the patients on Liver biopsy samples, all of which showed signs of fibrosis but not cirrhosis. One of the patients (aged 9 years) developed a Liver Adenoma which later resolved. All patients are currently doing well. Their clinical symptoms have improved with age and treatment. These cases add to the current knowledge of clinical variability in patients with PHKG2 mutations. Long term studies, involving follow-up of these patients into adulthood, are needed.
Rotchell, Jeanette M.. - One of the best experts on this subject based on the ideXlab platform.
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A novel population health approach: Using fish retinoblastoma gene profiles as a surrogate for humans.
'Elsevier BV', 2009Co-Authors: Rotchell, Jeanette M.., Lyons, Brett P.., Stentiford, Grant D.., Du Corbier, Frances A., Liddle, Andrew R., Ostrander, Gary K.Abstract:Retinoblastoma, a tumor suppressor gene, is frequently mutated in diverse types of human tumors. We have previously shown that two types of fish tumor, eye and Liver, also possess mutant Rb genes. Our aim is to determine if the Rb allele status is linked to environmentally-induced cancer and whether this information in fish can be used to predict future phenotype. This is a proof-of-concept investigation to elucidate if fish may act as surrogates in assessing pollution-induced tumor incidence and inform regulatory authorities of potential long-term population health consequences. Marine flatfish, Limanda limanda, that display either normal Liver histopathology. Liver Adenoma or Liver hepatocellular carcinoma were analysed for the presence of Rb gene alterations. Several Rb alterations were detected in the fish displaying Adenoma and carcinoma, and not in the surrounding normal tissue from the same individuals. The profile is similar to that reported in humans in that they spread across the gene, particularly exons 8-23, and a functionally important region of the protein. This Rb allele data was then used to build statistical classifier sets, linking Rb status with tumor pathology. Further flatfish caught from coastal-water areas of differing contaminant burden around the UK were subsequently analysed for the presence of Rb alterations. Using novel pattern matching statistics of the classifier sets compared with the coastal samples, the coastal fish were considered more similar to the characterised disease phenotype than the normal phenotype. Preliminary data suggests that using a statistical approach, based on classifying sets of histopathologically-defined tumor states, makes it possible to predict the phenotype of wild fish based on the status of the Rb allele. Since the Rb gene is orthologous, fish populations could act as surrogates for human populations in an eco-epidemiological investigation of the combined roles of genetics and environmental exposures in the tumorigenesis process
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A novel population health approach: using fish retinoblastoma gene profiles as a surrogate for humans
'Elsevier BV', 2008Co-Authors: Rotchell, Jeanette M.., Lyons, Brett P.., Stentiford, Grant D.., Du Corbier, Frances A., Liddle, Andrew R., Ostrander, Gary K.Abstract:Retinoblastoma, a tumor suppressor gene, is frequently mutated in diverse types of human tumors. We have previously shown that two types of fish tumor, eye and Liver, also possess mutant Rb genes. Our aim is to determine if the Rb allele status is linked to environmentally-induced cancer and whether this information in fish can be used to predict future phenotype. This is a proof-of-concept investigation to elucidate if fish may act as surrogates in assessing pollution-induced tumor incidence and inform regulatory authorities of potential long-term population health consequences. Marine flatfish, Limanda limanda, that display either normal Liver histopathology. Liver Adenoma or Liver hepatocellular carcinoma were analysed for the presence of Rb gene alterations. Several Rb alterations were detected in the fish displaying Adenoma and carcinoma, and not in the surrounding normal tissue from the same individuals. The profile is similar to that reported in humans in that they spread across the gene, particularly exons 8-23, and a functionally important region of the protein. This Rb allele data was then used to build statistical classifier sets, linking Rb status with tumor pathology. Further flatfish caught from coastal-water areas of differing contaminant burden around the UK were subsequently analysed for the presence of Rb alterations. Using novel pattern matching statistics of the classifier sets compared with the coastal samples, the coastal fish were considered more similar to the characterised disease phenotype than the normal phenotype. Preliminary data suggests that using a statistical approach, based on classifying sets of histopathologically-defined tumor states, makes it possible to predict the phenotype of wild fish based on the status of the Rb allele. Since the Rb gene is orthologous, fish populations could act as surrogates for human populations in an eco-epidemiological investigation of the combined roles of genetics and environmental exposures in the tumorigenesis process. (C) 2008 Elsevier Inc. All rights reserved
A Lachaux - One of the best experts on this subject based on the ideXlab platform.
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Liver transplantation for glycogen storage disease types i iii and iv
European Journal of Pediatrics, 1999Co-Authors: Dietrich Matern, Thomas E Starzl, W Arnaout, J Barnard, J S Bynon, Anil Dhawan, J Emond, E B Haagsma, G Hug, A LachauxAbstract:Glycogen storage disease (GSD) types I, III, and IV can be associated with severe Liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for Liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of Liver Adenoma and renal insufficiency. Nine type I and 3 type III patients have received Liver transplants because of poor metabolic control, multiple Liver Adenomas, or progressive Liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether Liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post Liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were Liver transplanted because of progressive Liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for Liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making.
Anne Roscher - One of the best experts on this subject based on the ideXlab platform.
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the natural history of glycogen storage disease types vi and ix long term outcome from the largest metabolic center in canada
Molecular Genetics and Metabolism, 2014Co-Authors: Julian Raiman, Anne Roscher, Jaina Patel, Stacy Hewson, Laura Nagy, Annette Feigenbaum, Jonathan B Kronick, Andreas SchulzeAbstract:Abstract Objectives Glycogen storage disease (GSD) types VI and IX are caused by phosphorylase system deficiencies. To evaluate the natural history and long-term treatment outcome of the patients with GSD-VI and -IX, we performed an observational retrospective case study of 21 patients with confirmed diagnosis of GSD-VI or -IX. Methods All patients with GSD-VI or -IX, diagnosed at The Hospital for Sick Children, were included. Electronic and paper charts were reviewed for clinical features, biochemical investigations, molecular genetic testing, diagnostic imaging, long-term outcome and treatment by two independent research team members. All information was entered into an Excel database. Results We report on the natural history and treatment outcomes of the 21 patients with GSD-VI and -IX and 16 novel pathogenic mutations in the PHKA2, PHKB, PHKG2 and PYGL genes. We report for the first time likely Liver Adenoma on Liver ultrasound and Liver fibrosis on Liver biopsy specimens in patients with GSD-VI and mild cardiomyopathy on echocardiography in patients with GSD-VI and -IXb. Conclusion We recommend close monitoring in all patients with GSD-VI and -IX for the long-term Liver and cardiac complications. There is a need for future studies if uncooked cornstarch and high protein diet would be able to prevent long-term complications of GSD-VI and -IX.