The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Danika L. Bannasch - One of the best experts on this subject based on the ideXlab platform.
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mutations in the slc2a9 gene cause hyperuricosuria and hyperuricemia in the dog
PLOS Genetics, 2008Co-Authors: Danika L. Bannasch, Nili Karmi, Noa Safra, Amy E Young, R S Schaible, G V LingAbstract:Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals.
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linkage analysis with an interbreed backcross maps Dalmatian hyperuricosuria to cfa03
Mammalian Genome, 2006Co-Authors: Noa Safra, Robert H Schaible, Danika L. BannaschAbstract:Dalmatians, like humans, excrete uric acid in their urine. All other dogs and most mammals excrete allantoin, a water-soluble compound that is further along the purine degradation pathway. Excretion of uric acid at high concentrations (hyperuricosuria) predisposes Dalmatians to the formation of urinary urate calculi. Hyperuricosuria (huu) is found in all Dalmatians tested and is inherited as an autosomal recessive trait. A genome scan and linkage analysis performed on a Dalmatian × Pointer interbreed backcross detected a single linked marker, REN153P03, located on CFA03. Haplotype analysis of the region around this marker defined a 3.3-Mb interval flanked by single recombination events. This interval, which contains the huu mutation, is estimated to include 24 genes.
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exclusion of urate oxidase as a candidate gene for hyperuricosuria in the Dalmatian dog using an interbreed backcross
Journal of Heredity, 2005Co-Authors: Noa Safra, Robert H Schaible, G V Ling, Danika L. BannaschAbstract:Hyperuricosuria, an autosomal recessive disorder, is characterized by high levels of uric acid in the urine of Dalmatian dogs. Whereas high levels of uric acid are known to be caused by the silencing of the urate oxidase (uox) gene in humans and higher primates, the molecular basis for the Dalmatian defect is unknown. Transplantation studies show that the organ responsible for the Dalmatian phenotype is the liver, which is where urate oxidase is exclusively expressed and uric acid is converted into allantoin. We cloned and sequenced the canine uox cDNA and compared the sequence between a Dalmatian and non-Dalmatian dog. No change in cDNA sequence was identified. A Dalmatian 3 pointer backcross family was used to track the segregation of microsatellite markers surrounding the urate oxidase locus. The uox gene was excluded for Dalmatian hyperuricosuria based on the cDNA sequence identity and negative LOD scores.
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exclusion of galectin 9 as a candidate gene for hyperuricosuria in the Dalmatian dog
Animal Genetics, 2004Co-Authors: Danika L. Bannasch, Robert H Schaible, Jeanne R Ryun, Michael J Bannasch, Matthew Breen, G V LingAbstract:Summary All Dalmatian dogs have an inherited defect in purine metabolism leading to high levels of uric acid excretion in their urine (hyperuricosuria) rather than allantoin, the normal end product of purine metabolism in all other breeds of dog. Transplantation experiments have demonstrated that the defect is intrinsic to the liver and not the kidney. Uricase, the enzyme involved in the breakdown of urate into allantoin, has been shown to function in Dalmatian liver cells. Therefore, candidate genes for this defect include transporters of urate, a salt of uric acid, across cell membranes. We excluded one such urate transporter candidate, galectin 9, using a Dalmatian × Pointer backcross in which hyperuricosuria was segregating.
Enrico Benedetti - One of the best experts on this subject based on the ideXlab platform.
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Multiple intrasplenic hepatocyte transplantations in the Dalmatian dog
Surgery, 2000Co-Authors: Ty B. Dunn, Norman H. Kumins, Vandad Raofi, Dawn M. Holman, Michael Mihalov, Jackie Blanchard, Christiana Rastellini, Enrico BenedettiAbstract:Abstract Background: Hepatocyte transplantation is an attractive potential treatment for liver-based inborn errors of metabolism and for fulminant hepatic failure. Dalmatian dogs have a metabolic error that results in hyperuricosuria. This report focuses on the effect of multiple, sequential intrasplenic transplants of fresh and cryopreserved hepatocytes in Dalmatians. Methods: Dalmatians underwent intrasplenic hepatocyte transplantation with hepatocytes taken from healthy mongrels. Dalmatian urinary uric acid excretion was measured preoperatively, and this served as the control value. Three hepatocyte transplantations were performed at 30-day intervals—the first with freshly isolated cells,and both the second and the third with cryopreserved hepatocytes from the same donor. Urinary uric acid excretion was measured postoperatively twice per week. Results: The urinary uric acid excretion decreased an average of 54% after the first hepatocyte transplantation. The effect was transient and lasted an average of 22 days (range, 19-50 days). Subsequent intrasplenic hepatocyte transplantation with cryopreserved hepatocytes resulted in similar decreases in urinary uric acid excretion. Each transplant resulted in a significant decrease in urinary uric acid excretion when compared with baseline values (P =
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INTRASPLENIC HEPATOCYTE ALLOTRANSPLANTATION IN Dalmatian DOGS WITH AND WITHOUT CYCLOSPORINE IMMUNOSUPPRESSION1
Transplantation, 1997Co-Authors: Enrico Benedetti, John P. Kirby, Massimo Asolati, Jacqueline Blanchard, M. Ward, Robert H. Williams, Terry A. Hewett, Magali J. Fontaine, Raymond PollakAbstract:Hepatocyte allotransplantation has been performed successfully in several small animal models for the amelioration of inborn metabolic errors. Before a human clinical trial of hepatocyte allotransplantation can be attempted, preliminary experience in a large animal model is needed. We transplanted isolated mongrel hepatocytes into the spleen of Dalmatians in the attempt to cure their inborn error of uric acid metabolism. Of 10 Dalmatian recipients, two that received 9-10 x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes and were randomized either to no treatment or to oral cyclosporine (CsA). Levels of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the four nonimmunosuppressed Dalmatians, a reproducible average reduction in urinary uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline within 14 days. In the CsA-immunosuppressed Dalmatians, the average decline in UUAEx was 30%. The partial correction of the metabolic defect persisted for an average of 25 days in three immunosuppressed dogs, whereas in one dog, the partial correction lasted for over 90 days. No change in UUAEx was observed in two Dalmatians that underwent sham laparotomy and intrasplenic injection of saline solution; CsA given alone to Dalmatians did not modify UUAEx. We conclude that the Dalmatian dog is a valuable large animal model for studies of the role of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.
Drago Štambuk - One of the best experts on this subject based on the ideXlab platform.
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Information Subsystem of Total Hardness (Ca + Mg) as a Database for Studying Its Influence on Human Health
Journal of Medical Systems, 2005Co-Authors: Nives Štambuk-giljanović, Drago ŠtambukAbstract:Dalmatia (Southern Croatia) belongs to the Dinaric karst region. The permeability of karst soil allows a great quantity of dissolved organic and toxic matter rendering it hygienically unsafe. The hinterland of the Dinaric karst region is relatively scarcely populated since the largest agglomeration of population and industry is in the coastal zones. Hence, most of the surface flow have preserved their natural characteristics. The water supply authorities and health care institutions are especially interested in observing and monitoring water quality. A relational database has been developed for carrying out chemical analyses expressed by total hardness (Ca + Mg) since it is necessary to organize and integrate a large number of analytical and ecological health-data. The database can serve as a methodological platform for the study of environmental factors influencing human health. The prototype database consists of data obtained by investigations which have been conducted by the Water Examination Department of the Public Health Institute, Split–Dalmatian County (Croatia) and the University of Split Medical School. The database currently contains more than 3000 data.
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Information Subsystem of the Ca/Mg Ratio as a Database for Studying Its Influence on Human Health
Journal of Medical Systems, 2005Co-Authors: Nives Štambuk-giljanović, Drago ŠtambukAbstract:Dalmatia is situated in the Dinaric karst in Southern Croatia. It is characterized by insufficient quantities of water during the summer months and a relatively excessive amount of rainfall during the winter and spring months. Other hydrographic characteristics of Dinaric carst include scarce and long surface streamflows with a few tributaries with changeable capacities, a small number of springs, and a relatively great number of submarine springs along the coast. The water supply and health-care institutions are especially interested in observing and monitoring water quality. A relational database has been developed for carrying out chemical analyses expressed by the Ca/Mg ratio since it is necessary to organize and integrate a large number of analytical and ecological health data. The database can serve as a methodological platform for the study of environmental factors influencing human health. The prototype database consists of data obtained by investigations which have been conducted by the water Examination Department of the Public Health Institute of the Split Dalmatian county (Croatia) University of Split Medical School. The database currently contains more than 2500 data.
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Information Subsystem of the Difference Between Anions Sum and Hardness of Water and Its Influence on Human Health
Journal of Medical Systems, 2000Co-Authors: Nives Štambuk-giljanović, Drago Štambuk, Berezina Matoković, Neven Elezović, Nilia JelićAbstract:Underground and surface waters in Dalmatia (Southern Croatia) have relatively preserved their natural characteristics since the greatest agglomeration of population and industry is located along the coast. The danger of pollution with fecal microorganism and products of biological decomposition is the most immediate problem but can be efficiently eliminated by water chlorination. The ecological need to sum up the work on water quality examination and estimation of future water quality trends resulted in water quality monitoring, i.e. in human health monitoring. It is necessary for large number of analytical and ecological health data to organize them from the informatical aspect into databases, the relational database for chemical analysis studying (the difference between anions sum and hardness) as methodological base for studying the ecological factors that influence human health defined in this paper. Results used for the prototype implementation subsystem of the chemical water analysis control are based on the investigations of Water Examination Department of the Public Health Institute of the Split-Dalmatian County (Croatia). Over 3400 data are comprised what is the sufficient examination sample. The software used included Win '95, Mo '97, and Paradox 4,5, while the hardware used included Pentium II 300 MHz, floppy, 128 MB RAM HDD 4,3 GB, CD × 24, HP DeskJet 710C.
G V Ling - One of the best experts on this subject based on the ideXlab platform.
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mutations in the slc2a9 gene cause hyperuricosuria and hyperuricemia in the dog
PLOS Genetics, 2008Co-Authors: Danika L. Bannasch, Nili Karmi, Noa Safra, Amy E Young, R S Schaible, G V LingAbstract:Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals.
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exclusion of urate oxidase as a candidate gene for hyperuricosuria in the Dalmatian dog using an interbreed backcross
Journal of Heredity, 2005Co-Authors: Noa Safra, Robert H Schaible, G V Ling, Danika L. BannaschAbstract:Hyperuricosuria, an autosomal recessive disorder, is characterized by high levels of uric acid in the urine of Dalmatian dogs. Whereas high levels of uric acid are known to be caused by the silencing of the urate oxidase (uox) gene in humans and higher primates, the molecular basis for the Dalmatian defect is unknown. Transplantation studies show that the organ responsible for the Dalmatian phenotype is the liver, which is where urate oxidase is exclusively expressed and uric acid is converted into allantoin. We cloned and sequenced the canine uox cDNA and compared the sequence between a Dalmatian and non-Dalmatian dog. No change in cDNA sequence was identified. A Dalmatian 3 pointer backcross family was used to track the segregation of microsatellite markers surrounding the urate oxidase locus. The uox gene was excluded for Dalmatian hyperuricosuria based on the cDNA sequence identity and negative LOD scores.
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exclusion of galectin 9 as a candidate gene for hyperuricosuria in the Dalmatian dog
Animal Genetics, 2004Co-Authors: Danika L. Bannasch, Robert H Schaible, Jeanne R Ryun, Michael J Bannasch, Matthew Breen, G V LingAbstract:Summary All Dalmatian dogs have an inherited defect in purine metabolism leading to high levels of uric acid excretion in their urine (hyperuricosuria) rather than allantoin, the normal end product of purine metabolism in all other breeds of dog. Transplantation experiments have demonstrated that the defect is intrinsic to the liver and not the kidney. Uricase, the enzyme involved in the breakdown of urate into allantoin, has been shown to function in Dalmatian liver cells. Therefore, candidate genes for this defect include transporters of urate, a salt of uric acid, across cell membranes. We excluded one such urate transporter candidate, galectin 9, using a Dalmatian × Pointer backcross in which hyperuricosuria was segregating.
Nives Štambuk-giljanović - One of the best experts on this subject based on the ideXlab platform.
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Information Subsystem of Total Hardness (Ca + Mg) as a Database for Studying Its Influence on Human Health
Journal of Medical Systems, 2005Co-Authors: Nives Štambuk-giljanović, Drago ŠtambukAbstract:Dalmatia (Southern Croatia) belongs to the Dinaric karst region. The permeability of karst soil allows a great quantity of dissolved organic and toxic matter rendering it hygienically unsafe. The hinterland of the Dinaric karst region is relatively scarcely populated since the largest agglomeration of population and industry is in the coastal zones. Hence, most of the surface flow have preserved their natural characteristics. The water supply authorities and health care institutions are especially interested in observing and monitoring water quality. A relational database has been developed for carrying out chemical analyses expressed by total hardness (Ca + Mg) since it is necessary to organize and integrate a large number of analytical and ecological health-data. The database can serve as a methodological platform for the study of environmental factors influencing human health. The prototype database consists of data obtained by investigations which have been conducted by the Water Examination Department of the Public Health Institute, Split–Dalmatian County (Croatia) and the University of Split Medical School. The database currently contains more than 3000 data.
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Information Subsystem of the Ca/Mg Ratio as a Database for Studying Its Influence on Human Health
Journal of Medical Systems, 2005Co-Authors: Nives Štambuk-giljanović, Drago ŠtambukAbstract:Dalmatia is situated in the Dinaric karst in Southern Croatia. It is characterized by insufficient quantities of water during the summer months and a relatively excessive amount of rainfall during the winter and spring months. Other hydrographic characteristics of Dinaric carst include scarce and long surface streamflows with a few tributaries with changeable capacities, a small number of springs, and a relatively great number of submarine springs along the coast. The water supply and health-care institutions are especially interested in observing and monitoring water quality. A relational database has been developed for carrying out chemical analyses expressed by the Ca/Mg ratio since it is necessary to organize and integrate a large number of analytical and ecological health data. The database can serve as a methodological platform for the study of environmental factors influencing human health. The prototype database consists of data obtained by investigations which have been conducted by the water Examination Department of the Public Health Institute of the Split Dalmatian county (Croatia) University of Split Medical School. The database currently contains more than 2500 data.
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Information Subsystem of the Difference Between Anions Sum and Hardness of Water and Its Influence on Human Health
Journal of Medical Systems, 2000Co-Authors: Nives Štambuk-giljanović, Drago Štambuk, Berezina Matoković, Neven Elezović, Nilia JelićAbstract:Underground and surface waters in Dalmatia (Southern Croatia) have relatively preserved their natural characteristics since the greatest agglomeration of population and industry is located along the coast. The danger of pollution with fecal microorganism and products of biological decomposition is the most immediate problem but can be efficiently eliminated by water chlorination. The ecological need to sum up the work on water quality examination and estimation of future water quality trends resulted in water quality monitoring, i.e. in human health monitoring. It is necessary for large number of analytical and ecological health data to organize them from the informatical aspect into databases, the relational database for chemical analysis studying (the difference between anions sum and hardness) as methodological base for studying the ecological factors that influence human health defined in this paper. Results used for the prototype implementation subsystem of the chemical water analysis control are based on the investigations of Water Examination Department of the Public Health Institute of the Split-Dalmatian County (Croatia). Over 3400 data are comprised what is the sufficient examination sample. The software used included Win '95, Mo '97, and Paradox 4,5, while the hardware used included Pentium II 300 MHz, floppy, 128 MB RAM HDD 4,3 GB, CD × 24, HP DeskJet 710C.
