Browsing by Author "Miquel Poblete Juan Francisco"

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    Cholesterol saturation, not proteins or cholecystitis, is critical for crystal formation in human gallbladder bile
    (W. B. Saunders Co., 1998) Miquel Poblete Juan Francisco; Nuñez, Liliana; Amigo Boker, Ludwig Peter; González Bombardiere, Sergio Javier; Raddatz Echavarría, Alejandro; Rigotti Rivera, Attilio Gianpietro; Nervi Oddone, Flavio
    Biliary proteins are promoters of cholesterol crystallization in artificial model bile. However, their pathogenic importance for cholesterol precipitation in native gallbladder bile (GB) is uncertain. The aim of this study was to evaluate the significance of biliary lipids and proteins on cholesterol crystal detection time (ChCDT) of GB in patients with gallstones. Methods: ChCDT and concentrations of lipids, albumin, mucins, aminopeptidase N, alpha 1-acid glycoprotein, haptoglobin, and immunoglobulins (Igs) were measured in GB of 92 patients, 52 of whom had cholesterol gallstones. Results: ChCDT was markedly reduced in gallstone patients. Compared with patients without gallstones, they had a significant increase in cholesterol saturation and total protein, albumin, mucin, and IgG biliary concentrations. In univariate analysis, ChCDT of GB was significantly correlated with cholesterol saturation and total lipid, protein, Ig, aminopeptidase N, and alpha 1-acid glycoprotein concentrations. However, stepwise logistic regression analysis showed that only cholesterol saturation independently correlated to ChCDT. Gallbladder inflammation correlated with the concentration of Igs, but subtraction of IgG from GB did not modify the ChCDT. Conclusions: Biliary cholesterol transport and saturation, but not proteins, appear critical for the cholesterol crystallization abnormality observed in native bile from patients with gallstones.
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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.