Biomedical subjects

Achille Iolascon

Publications and source records attributed to Achille Iolascon.

39 records · Page 3Linked to original sources

PubMedDate not supplied

Gene expression analysis in HBV transgenic mouse liver: a model to study early events related to hepatocarcinogenesis.

Hepatitis B virus (HBV) is one of the major etiological factors responsible for the development of hepatocellular carcinoma (HCC). We used a transgenic mouse, containing HBV sequences, as a model system to unravel the molecular mechanisms of hepatocarcinogenesis induced by HBV. We chose this animal model because it consistently develops liver cancer after intermediate steps that mimic the natural history of HBV infection in humans. In this study, we focus our attention on the early events leading to liver cancer. We compared the gene expression profile of 3-month-old transgenic mice with that of 3-month-old wild-type (wt) animals. In the transgenic mouse, microarray data analysis showed a total of 45 significantly differentially expressed genes, 25 highly expressed (fold change > or =2; P = 0.0025), and 20 downregulated (fold change < or =0.5; P = 0.0025). These genes belong to several different functional categories such as the regulation of immunological response, transcription, intracellular calcium ion mobilization, regulation of cell cycle and proliferation, NF-kappab signal transduction cascades, and apoptosis. In particular, the upregulation of the antiapoptotic gene NuprI and the downregulation of the proapoptotic gene Bnip3 were found. This observation was supported by an in vitro apoptosis assay that showed downregulation of apoptosis in hepatocytes of HBV transgenic mouse compared with wt mice treated with staurosporine. In conclusion, our experimental approach allowed identification of new genes modulated by HBV and showed that the apoptotic process was deregulated in transgenic mouse hepatocytes. These data shed light on one possible mechanism by which HBV induces hepatocarcinogenesis.

Animals↗

PubMedDate not supplied

Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach.

BACKGROUND: Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disorder mainly caused by mutations in the nephrin gene (NPHS1). The frequency of this gene is highest in Finland but the condition occurs in all populations, with and without Finnish ancestry. The NPHS1 gene is located in the chromosomal region 19q13.1 and consists of 29 exons. METHODS: Polymerase chain reaction (PCR), restriction and sequence analyses were used to screen 15 CNF Italian patients for mutations in this gene. RESULTS: No Italian patients had the typical Finnish mutations, a 2bp deletion in exon 2 (Fin-major) and a nonsense mutation in exon 26 (Fin-minor). We found 13 mutations including deletions, insertions, nonsense and missense mutations. Seven of these have never been described before. We also found one nucleotide change in the promoter region and one common polymorphism. NPHS1 missense mutations were confirmed by analysis of a healthy control population. CONCLUSIONS: Our study provides further evidence that loss of function of the nephrin gene is the main cause of congenital nephrotic syndrome of the Finnish type in Italian patients.

Case-Control Studies↗

PubMedDate not supplied

LCAT deficiency: molecular and phenotypic characterization of an Italian family.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of lipoprotein metabolism, resulting from loss of function of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), a key enzyme in extracellular cholesterol metabolism and reverse cholesterol transport (RCT). The human LCAT gene has been mapped to chromosome band 16q22, and consists of 6 exons encoding for a mature protein of 416 amino acids. In the present study, we describe the molecular phenotype of a patient with classical LCAT deficiency and progressive renal failure. Sequence analysis of the LCAT gene showed 2 homozygous missense mutations: the common variant p.S208T, described as a homozygous change for the first time, and a missense mutation characterized by the substitution of Leu372 to Arg. Clinical, biochemical and renal histological studies were also performed to elucidate the functional effects of these variations. In the proband and his brother, LCAT activity and plasma cholesterol esterification rate (CER) were absent, while plasma LCAT concentrations were slightly reduced. By light microscopy, silver-stained renal biopsy specimens of the proband showed focal segmental glomerulosclerosis, while electron microscopy detected lipid deposits with both vacuolar lucent appearance and electron-dense lamellar structures within the mesangial matrix and glomerular basement membrane. This study describes for the first time the occurrence of two homozygous missense mutations as the common variant p.S208T and the mutation p.L372R in familial LCAT deficiency.

Adult↗