The objectives of this total project are the investigation of two states with deficient bilirubin metabolism: (1) the jaundiced (jj) Gunn rat (model for the human Crigler-Najjar Syndrome), and (2) the prolonged hyperbilirubinemia of breast-fed infants (breast-milk jaundice). My research has demonstrated significant differences between jj and normal JJ Gunn rats in hepatic microsomal lipid composition and microviscosity. Using a new HPLC method to separate and identify bilirubin conjugates. I have characterized jj, Jj and JJ Gunn rat bile pigments and their relationship to glucuronyl transferase activity. Human bilirubin conjugates have also been studied using a new simplified method of duodenal bile collection which utilizes a string rather than the traditional tube. I have initiated a prospective clinical protocol which examines three current hypotheses regarding the etiology of breast-milk jaundice. During the proposed extension the following activities will be performed: (1) The clinical breast-milk jaundice study involving approximately 150 neonates and their mothers will conclude data collection and analysis. (2) Bilirubin conjugation by intact human and rat hepatocytes (isolated hepatocyte suspensions and hepatocytes cultured on plastic, collagen gel and gel-mesh) will be characterized using quantitative HPLC methods. (3) Inhibition of bilirubin metabolism by matenial serum or breast milk will be investigated in the intact hapetocyte systems described above, thus complementing microsomal inhibition assays in progress. (4) The role of Gilbert's syndrome as a cause of neonatal hyperbilirubinemia will be addressed by studying the parents of neonates who participated in the breast-milk jaundice study noted above. (5) Work with Dr. Frank Siegel will address the mechanism of bilirubin's Central Nervous System toxicity. (6) The duodenal fluid sampling technique noted above and new HPLC methods will be used to investigate biliary excretion of bile pigments, bile salts and amino acids in patients with liver disease.
| Gourley, G R; Gourley, M F; Arend, R et al. (1989) The effect of saccharolactone on rat intestinal absorption of bilirubin in the presence of human breast milk. Pediatr Res 25:234-8 |
| Gourley, M F; Gourley, G R; Gilbert, E F et al. (1989) Alpha 1-antitrypsin deficiency and the PiMS phenotype: case report and literature review. J Pediatr Gastroenterol Nutr 8:116-21 |
| Goodman, G M; Gourley, G R (1988) Ascites complicating ventriculoperitoneal shunts. J Pediatr Gastroenterol Nutr 7:780-2 |
