The program aims to elucidate the underlying abnormalities in deranged transport of amino acids and sugar with emphasis on cystinuria as the prototypic inherited transport abnormality, the Fanconi syndrome associated with several inherited metabolic diseases with its global disarray of solute transport systems and ontogenic events of the aminoaciduria of immaturity. The program will utilize cellular and subcellular systems as well as intact animal models to delineate the basic molecular events involved and will be focused on the application of cutting-edge methods such as mass spectrometry and NMR and DNA technology, to examine cellular transport events. The proposed research program consists of six projects all interrelated by their thematic aim, interlocking staff and shared techniques and three cores. These are: Project 1, Cystinuria and the Nature of the Renal Cystine-Lysine Transport System, Dr. Segal, Principal Investigator, Project 2, Chemical Models of the Fanconi Syndrome: Studies with 15N-GC-MS and 13C-NMR, Principal Investigator, Dr. Nissim, Project 3, Cultured Renal Epithelial Cells as Model Systems of Renal Transport Mechanisms, Principal Investigator, Dr. States, Project 4, Animal Models of Transport Disorders, Principal Investigator, Drs. Bovee and Segal, Project 5, Examination of Human Intestinal Amino Acid Transport Systems, Dr. McNamara, Project 6, Ontogeny and Regulation of Transport in Renal Membranes, Dr. Hsu, Core A, Membrane and Tubule Preparation, Dr. McNamara, Core B Analytical Chromatography., Dr. Yandrasitz, and Core C, Administrative, Dr. Segal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK040555-05
Application #
3095554
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1988-09-01
Project End
1993-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hsu, B Y; Wehrli, S L; Yandrasitz, J R et al. (1994) Renal brush border membrane lipid composition in Basenji dogs with spontaneous idiopathic Fanconi syndrome. Metabolism 43:1073-8
Hsu, B Y; McNamara, P D; Mahoney, S G et al. (1992) Membrane fluidity and sodium transport by renal membranes from dogs with spontaneous idiopathic Fanconi syndrome. Metabolism 41:253-9
McNamara, P D; Rea, C T; Segal, S (1992) Ion dependence of cystine and lysine uptake by rat renal brush-border membrane vesicles. Biochim Biophys Acta 1103:101-8
States, B; Harris, D; Segal, S (1991) Differences between OK and LLC-PK1 cells: cystine handling. Am J Physiol 261:C8-16
McNamara, P D; Rea, C T; Segal, S (1991) Expression of rat jejunal cystine carrier in Xenopus oocytes. J Biol Chem 266:986-9
Reynolds, R A; Mahoney, S G; McNamara, P D et al. (1991) The influence of pH on cystine and dibasic amino acid transport by rat renal brushborder membrane vesicles. Biochim Biophys Acta 1074:56-61
States, B; Segal, S (1990) Cystine and dibasic amino acid uptake by opossum kidney cells. J Cell Physiol 143:555-62
States, B; Reynolds, R; Lee, J et al. (1990) Cystine uptake by cultured cells originating from dog proximal tubule segments. In Vitro Cell Dev Biol 26:105-12
Nissim, I; States, B (1989) Ammoniagenesis by cultured human renal cortical epithelial cells: study with 15N. Am J Physiol 256:F187-96
Hsu, B Y; McNamara, P D; Cariola, C M et al. (1989) Characteristics of L-proline and sodium transport in renal brush border membranes isolated from 7-day-old and adult rats. Biosci Rep 9:709-19