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1.
Kidney Int ; 68(3): 966-71, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16105027

ABSTRACT

BACKGROUND: The quantitative genetics of urine calcium excretion has not been established. It is a trait of interest because hypercalciuria is commonly found in subjects with nephrolithiasis. The aim of this study was to model the segregation of this trait in a sample of French-Canadian families ascertained through a stone former. METHODS: Major gene, polygenic, and mixed models were fit to 24-hour urine calcium excretion from 567 individuals in 221 nuclear families, while simultaneously taking into account gender, age at examination, body mass index (BMI), and the use of thiazide drugs. The nuclear families were extracted from 154 pedigrees, some of which were four generations, with at least two siblings with a history of calcium stones. RESULTS: All the proposed genetic models fit the data significantly better than the null model. The most parsimonious model was the mixed codominant/polygenic model but it was statistically indistinguishable from the single-gene codominant model. In both of these models the heritability attributable to the major gene was estimated to be 0.58. CONCLUSION: Our results suggest that a major gene with a relatively large effect on variation in urine calcium excretion is segregating in French-Canadian families with stone formers. This implies that the power of quantitative trait segregation analysis of urine calcium excretion may be increased in these families, and results indicate that it should be feasible to genetically map the quantitative trait locus.


Subject(s)
Calcium/urine , Genetic Variation , Kidney Calculi/genetics , Kidney Calculi/urine , Models, Genetic , Adult , Canada , Family Health , Female , Humans , Male , Middle Aged
2.
Biomaterials ; 26(13): 1515-22, 2005 May.
Article in English | MEDLINE | ID: mdl-15522753

ABSTRACT

Microencapsulation in semi-permeable membranes protects transplanted cells against immune destruction. Microcapsule strength is critical. We describe a method to microencapsulate living cells in alginate-poly-L-lysine (PLL)-alginate membranes with covalent links between adjacent layers of microcapsule membranes, while preserving the desired membrane molecular weight cut-off (MWCO) and microencapsulated cell viability. A heterobifunctional photoactivatable cross-linker, N-5-azido-2-nitrobenzoyloxysuccinimide (ANB-NOS) was used. The N-hydroxysuccinimide ester group of ANB-NOS was covalently linked to PLL. Islets of Langerhans were immobilized in alginate beads, incubated in PLL-ANB-NOS and again in alginate. Upon illumination with UVA, covalent links were created between the phenyl azide residue of ANB-NOS and alginate from both the core bead and the outer coating. Covalently linked microcapsules remained intact after 3 years in a strong alkaline buffer (pH 12), whereas standard microcapsules disappeared within 45 s in the same solution. A standardized mechanical stress broke 22-fold more standard than covalently linked microcapsules. The MWCO and microencapsulated cell viability were similar with standard and covalently linked microcapsules. These microcapsules, extremely resistant to chemical and mechanical stresses, will be useful in numerous applications.


Subject(s)
Alginates/chemistry , Cell Culture Techniques/methods , Islets of Langerhans Transplantation/methods , Islets of Langerhans/cytology , Islets of Langerhans/physiology , Pancreas, Artificial , Polylysine/chemistry , Alginates/analysis , Animals , Cell Survival/physiology , Cells, Cultured , Coated Materials, Biocompatible/analysis , Coated Materials, Biocompatible/chemistry , Compressive Strength , Cross-Linking Reagents/chemistry , Materials Testing , Membranes, Artificial , Molecular Weight , Permeability , Polylysine/analysis , Rats , Rats, Wistar , Tissue Engineering/methods
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