Browsing by Author "Pimentel González, Eduardo Fernando"

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    Biliary aminopeptidase-N and the cholesterol crystallization defect in cholelithiasis
    (British Medical Journal Publishing Group, 1995) Núñez, L.; Amigo Boker, Ludwig Peter; Mingrone, G.; Rigotti Rivera, Attilio Gianpietro; Puglielli, L.; Raddatz Echavarría, Alejandro; Pimentel González, Eduardo Fernando; Greco, A.; González, S.; Garrido Negri, Jorge; Miquel Poblete, Juan Francisco; Nervi Oddone, Flavio; Pontificia Universidad Católica de Chile. Departamento de Gastroenterología y Centro para la Prevención y tratamiento del Cáncer Digestivo; Institute of Clinical Medicine, Universita Cattolica del Sacro Cuore, Rome, Italy
    Several biliary proteins have cholesterol crystallisation promoting activity. One of these glycoproteins is aminopeptidase-N, a canalicular ectoenzyme. This study attempted to localise aminopeptidase-N along the biliary tree, to assess its concentration in a series of 98 patients subjected to abdominal surgery, 40 of them without gap stones, and to correlate its concentration with cholesterol crystal formation time of gall bladder bile. Aminopeptidase-N was isolated from purified native biliary vesicles. A specific polyclonal rabbit anti-aminopeptidase-N antibody was prepared for quantitative immunoblotting and for immunolocalisation. Tissue was obtained from liver biopsy specimens and from gall bladders removed at surgery because of gall stone disease. Aminopeptidase-N was immunolocalised to the apical membranes of hepatocytes and to the apical pole of ductular and gall bladder mucosal cells. The nucleation time of gall bladder bile was mean (SD) 4 (3) days in the gall stone group, compared with 21 (18) days in the control group (p < 0.001). Total absolute biliary protein and aminopeptidase-N concentrations were similar in both the control and gall stone patients. There was a reciprocal significant correlation, however, between the nucleation time and the relative aminopeptidase-N concentration (r = -0.35, p < 0.01) only in the gall stone group of patients, This study shows that this apical transmembrane ectoenzyme with cholesterol crystallisation promoting activity is present along the biliary tree and the hepatocyte. These findings support the concept that high concentrations or qualitative changes of biliary aminopeptidase-N contribute to cholesterol gall stone formation.
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    Tp53 Abnormalities Are Frequent and Early Events in the Sequential Pathogenesis of Gallbladder Carcinoma
    (2005) Moreno, M.; Pimentel González, Eduardo Fernando; Gazdar, Adi F.; Wistuba Oyarzun, Ignacio; Miquel Poblete Juan Francisco
    Background: Gallbladder carcinoma (GBC) is a frequent neoplasm in Hispanic and native American populations. GBC is preceded by gallstones, chronic cholecystitis and dysplastic changes of the gallbladder epithelium. The knowledge of the molecular events involved in its pathogenesis is scarce. Aims: We investigated the role of TP53 inactivation in the sequential pathogenesis of GBC. Methods: Invasive tumor-, dysplastic- and histologically normal GB ep ithelial-cells were obtained from archival formalin fixed tissues from GBC and GB from gallstone pa tients without GBC. Normal GB epithelia from 5 non-gallstone specimens were also studied. DNA extracted was examined for loss of heterozygosity (LOH) using 2 microsatellite markers and for TP53 mutations at exons 5 to 8. Results: GBCs demonstrated a high frequency of LOH (81%) and mutation (67%), and both abnormalities indicating gene inactivation were detected in 52%. Similar frequency of TP53 Abnormalities are frequent and early events in the sequential pathogenesis of gallbladder carcinomaivation (38%) were detected in their accompanying normal and dysplastic epithelia. Noteworthy, one third of normal and dysplastic epithelia obtained from GBs of gallstone patients without GBC demonstrated either TP53 allele loss or mutation, but gene inactivation was less frequent (11%). Most mutations affected exons 5 and 7, and they were more frequently missense point mutations. The same TP53 mutation was de tected in only a subset (27%) of comparisons between non-malignant epithelia adjacent to GBCs, indicating that TP53 mutation occurs independently at several epithelial foci. Conclusions: These findings indicate that TP53 abnormalities are early and frequent events in the pathogenesis of GBC, starting from chronic cholecystitis.