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G Frasca

Publications and source records attributed to G Frasca.

At least 19 recordsLinked to original sources
PubMed2006

Cis and trans regulatory elements in NPHS2 promoter: implications in proteinuria and progression of renal diseases.

Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, -116T, and -535 insCTTTTTT(3)) were found determining strong downregulation (-73, -59, and -82%, respectively) of the reporter gene expression when transfected in podocytes. Electrophoretic mobility shift assay experiments showed that all wild-type variants (-51G, -116C, and -535 insCTTTTTT(2)) formed specific DNA-protein complexes with podocyte nuclear extracts that were abolished by the presence of the rare forms (-51T, -116T, and -535 insCTTTTTT(3)). In the case of -51G, upstream stimulatory factor-1 (USF1) was identified as the specific trans element in accord to binding inhibition experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and 237 focal segmental glomerulosclerosis) evidenced that -116/-51 and -535/P2OL formed two blocks in strong linkage disequilibrium in both normal and pathological cohorts. The high NPHS2 promoter profile -116C/-51G haplotype was more frequent in patients with IgA nephropathy (P-value=0.005) and was associated with a better clinical outcome in terms of proteinuria and creatinine levels. Overall our study describes functional variants of NPHS2 promoter and characterizes trans-acting elements that modulate podocin expression in the kidney. High producer NPHS2 promoter haplotypes seem protective in patients with chronic glomerular diseases.

Adolescent↗
PubMed2004

Novel neuronal targets for the acetylcholinesterase inhibitor donepezil.

The effects of the acetylcholinesterase inhibitor donepezil on cell viability and proliferation events have been analysed in SH-SY5Y human neuroblastoma cells. Short- (48 h) or long-term (7 days) exposure of SH-SY5Y cells to donepezil (100 nM-10 microM) induced a concentration-dependent inhibition of cell proliferation that was not modified by muscarinic and nicotinic receptor antagonists, or mimicked by galantamine, and was not related to induction of apoptosis. By analysing the distribution profile of cell populations within the cell cycle following treatment with 10 microM donepezil, a reduction of cells in the S-G2/M phases of the cycle and a parallel increase of the G0/G1 population were observed. In addition, the expression of two cyclins of the G1/S and G2/M transitions, cyclin E and cyclin B, was significantly reduced in donepezil-treated cells. In contrast, the expression of the cell cycle inhibitor p21 rapidly (6 h) increased following exposure to the drug. Finally, donepezil increased the expression of the neuronal marker MAP-2 in selected subpopulations of SH-SY5Y cells, suggesting that the effect on cell proliferation by donepezil may correlate to a trend to neuronal differentiation.

Cell Cycle↗
PubMed2002

Food sources of carbohydrates in a European cohort of adults.

OBJECTIVE: To describe the average consumption of carbohydrate-providing food groups among study centres of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Of the 27 redefined EPIC study centres, 19 contributed subjects of both genders and eight centres female participants only (men, women, after exclusion of subjects under 35 and over 74 years of age from the original 36 900 total). Dietary data were obtained using the 24-hour recall methodology using the EPIC-SOFT software. The major sources of dietary carbohydrate were identified, and 16 food groups were examined. RESULTS: The 10 food groups contributing most carbohydrate were bread; fruit; milk and milk products; sweet buns, cakes and pies; potato; sugar and jam; pasta and rice; vegetables and legumes; crispbread; and fruit and vegetable juices. Consumption of fruits as well as vegetables and legumes was higher in southern compared with northern centres, while soft drinks consumption was higher in the north. Italian centres had high pasta and rice consumption, but breakfast cereal, potato, and sweet buns, cakes and pies were higher in northern centres. In Sweden, lower bread consumption was balanced with a higher consumption of crispbread, and with sweet buns, cakes and pies. Overall, men consumed higher amounts of vegetables and legumes, bread, soft drinks, potatoes, pasta and rice, breakfast cereal and sugar and jam than women, but fruit consumption appeared more frequent in women. CONCLUSION: The study supports the established idea that carbohydrate-rich foods chosen in northern Europe are different from those in the Mediterranean region. When comparing and interpreting diet-disease relationships across populations, researchers need to consider all types of foods.

Adult↗
PubMed2002

Soy product consumption in 10 European countries: the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

OBJECTIVE: The aim of this study was to describe the variation of soy product intake in 10 European countries by using a standardised reference dietary method. A subsidiary aim was to characterise the pattern of soy consumption among a sub-group of participants with a habitual health-conscious lifestyle (HHL), i.e. non-meat eaters who are fish eaters, vegetarians and vegans. DESIGN: A 24-hour dietary recall interview (24-HDR) was conducted among a sample (5-12%) of all cohorts in the European Prospective Investigation into Cancer and Nutrition (EPIC). Study participants totalled 35 955 after exclusion of subjects younger than 35 or older than 74 years of age. Soy products were subdivided into seven sub-groups by similarity. Distribution of consumption and crude and adjusted means of intake were computed per soy product group across countries. Intake of soy products was also investigated among participants with an HHL. RESULTS: In total, 195 men and 486 women reported consuming soy products in the 24-HDR interview. Although soy product intake was generally low across all countries, the highest intake level was observed in the UK, due to over-sampling of a large number of participants with an HHL. The most frequently consumed soy foods were dairy substitutes in the UK and France and beans and sprouts among mid-European countries. For both genders, the sub-group of soy dairy substitutes was consumed in the highest quantities (1.2 g day-1 for men; 1.9 g day-1 for women). Participants with an HHL differed substantially from others with regard to demographic, anthropometric and nutritional factors. They consumed higher quantities of almost all soy product groups. CONCLUSIONS: Consumption of soy products is low in centres in Western Europe. Soy dairy substitutes are most frequently consumed. Participants with an HHL form a distinct sub-group with higher consumptions of fruit, vegetables, legumes, cereals and soy products compared with the other participants.

Adult↗
PubMed1994

P-glycoprotein epitope mapping. I. Identification of a linear human-specific epitope in the fourth loop of the P-glycoprotein extracellular domain by MM4.17 murine monoclonal antibody to human multi-drug-resistant cells.

A new murine monoclonal antibody (MAb), MM4.17, to human multi-drug-resistant (MDR) cells was found to be reactive in an ELISA with a synthetic 16-amino acid peptide selected from the fourth loop of the P-glycoprotein extracellular domain. Immunohistochemistry indicated that this MAb reacted in human tissues in the same pattern as that previously found with other human-specific MAbs to P-glycoprotein. For a precise definition of the MM4.17 epitope, a peptide library consisting of overlapping 4- to 10-mer residues covering the entire P-glycoprotein-fragment was synthesized on polyethylene pins and tested for MAb binding. The results of this ELISA demonstrated that the MM4.17 epitope is constituted by the continuous-linear TRIDDPET amino-acid sequence (residues 750-757 of the human MDRI-P-glycoprotein). The MAb MM4.17 recognizes only the human MDRI-P-glycoprotein isoform, and excess TRIDDPET peptide blocks the binding of the MAb to MDR variants of CEM cells. These results demonstrate that the amino-acid sequence TRIDDPET from the human MDRI gene represents the first continuous-linear epitope identified in the P-glycoprotein extracellular domain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗