Alternative splicing of fibronectin pre-mRNA during aging.
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Aging↗
Biomedical subjects
C Vergani
Publications and source records attributed to C Vergani.
Association of a polymorphism in the Apo AI gene promoter with hyperalphalipoproteinemia.
The distribution of a polymorphism due to an Adenine to Guanine transition in the ApoAI gene has been studied in 136 women and 108 men, through amplification of the promoter region of the gene and allele-specific oligonucleotide hybridization. The allelic frequencies for the A allele were 0.10, 0.14 and 0.27 in women and 0.08, 0.17 and 0.14 in men for the lowest decile, intermediate group and the highest decile of HDL-cholesterol levels, respectively. Statistical analysis showed that the A allele was associated with high HDL-cholesterol levels in women, but not in men.
Alleles↗
High density lipoproteins: physiopathology and clinical relevance.
On September 13-14 1991 a Symposium on High Density Lipoproteins: Physiopathology and Clinical Relevance was held in Bellagio (Italy). This Symposium was aimed at discussing various aspects of HDL from epidemiology to the most recent advances in the understanding of HDL metabolism and factors (diets, drugs) affecting their levels.
Coronary Disease↗
Free radicals promote modifications in plasma high-density lipoprotein: nuclear magnetic resonance analysis.
The behavior of high-density lipoprotein (HDL) after free-radical-mediated oxidation was studied by incubating plasma HDL with chemical oxidizing systems (Cu++) in conditions similar to those used for low-density lipoprotein (LDL) chemical oxidation. Nuclear magnetic resonance (NMR) spectroscopy (1H and 31P) was used to evaluate the degree of oxidation and to characterize the oxidized products. The almost complete loss of polyunsaturated systems together with an appreciable decrease in choline peak demonstrates large-scale HDL-lipid degradation. The appearance of epoxide systems on fatty chains and the identification of oxidized cholesterol derivatives as cholesterol 5 alpha,6 alpha-epoxide, 5 beta,6 beta-epoxide, 7-keto, and 25-hydroxy confirm this picture. Phospholipid analysis indicates an alteration of the phospholipid profile in lyso-phosphatidylcholine (Lyso-PC) production and the disappearance of phosphatidylethanolamine (PE). This study shows that HDL is extensively degraded although there are no large variations in the classical oxidative monitors, lipid hydroperoxide (LPO) and thiobarbituric acid reactive substance (TBARS). Our results suggest that HDL is significantly modified when submitted to an oxidative process.
Cholesterol↗
Antioxidant activity of ubiquinone-3 in human low density lipoprotein.
The ability of ubiquinone-3, a short chain ubiquinone homologue, to prevent Cu2+ induced oxidation of human low density lipoprotein was investigated. The results are as follows: in the presence of ubiquinone-3 the extent of peroxidation, as determined by the formation of thiobarbituric acid reactive substances, was only one third of that found in its absence; the quinone can also prevent the fragmentation of apolipoprotein B-100 and the increase of the net negative surface charge of the particle.
Apolipoprotein B-100↗
Videoendoscopic pulmonary lobectomy for cancer.
A videothoracoscopic right lower pulmonary lobectomy is reported. The excision was done in a 71-year-old man suffering from an adenocarcinoma of the right lower lobe, with an apparent absence of lymphnodal and systemic metastasis. The procedure has been performed using four 10-mm cannulas and a minimal inframammary thoracotomy (4 cm) by inserting a chip camera linked to the thoracoscope and connected to external monitors. The lobar hilar structures were dissected and then sutured-divided with Endo-GIA R shots. The specimen was extracted through the minimal thoracotomy. The postoperative course was uneventful with minimal postoperative pain, and the patient was discharged after complete surgical recovery with excellent functional and cosmetic results. This procedure in selected patients is a new and promising possibility in chest videoendoscopic surgery.
Adenocarcinoma↗
Tissue-specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat.
Fibronectin isoforms are generated by the alternative splicing of a primary transcript derived from a single gene. In rat at least three regions of the molecule are involved: EIIIA, EIIIB, and V. This study investigated the splicing patterns of these regions during development and aging, by means of ribonuclease protection analysis. Between fetal and adult rat, the extent of inclusion of the EIIIA and/or EIIIB region in fibronectin mRNA varied according to the type of tissue analyzed; but the inclusion of the V region, and in particular the V25 alternative variant, was significantly higher in all fetal than in adult tissues. These data suggest a crucial role of the V25 variant, possibly related to its interaction with the alpha 4 beta 1 integrin receptor during development. On the other hand, during aging, the only significant change observed in the splicing pattern was a decrease in the EIIIA variant in brain. The high inclusion levels of the EIIIA and EIIIB regions in young adult brain suggest that these segments may play an important role in differentiated brain tissue. The decreasing levels of inclusion of the EIIIA segment in brain fibronectin mRNA during aging may be an age-related marker with functional consequences.
Aging↗
Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele.
The enzyme, lecithin cholesterol acyltransferase (LCAT), is responsible for the esterification of plasma cholesterol mediating the transfer of an acyl group from lecithin to the 3-hydroxy group of cholesterol. Deficiency of the enzyme is a well-known syndrome with a widespread geographic occurrence. We have cloned an allele from a patient homozygous for the LCAT deficiency. The only change that we could detect is a C to T transition in the fourth exon of the gene; this causes a substitution of Arg for Trp at position 147 of the mature protein. The functional significance of such a substitution with respect to the enzyme defect was demonstrated by transfecting the mutated LCAT gene in the cell line COS-1.
Alleles↗
Stability of DNA methylation of X-chromosome genes during aging.
The stability of DNA methylation during aging was assessed in two groups of young (5-20 years old) and old (85-95 years old) women in DNA from blood leukocytes. Three X-linked genes were investigated. Two, G6PD and GdX, are located on Xq28, on the inactivated portion of the X chromosome: demethylation of specific regions of both genes was shown previously to be directly correlated with gene reactivation. The third, MIC2, is located on the pseudoautosomal region of the X chromosome and escapes X inactivation. The 5' region of the G6PD and GdX genes and the body of the G6PD, GDX, and MIC2 genes were analyzed with specific DNA probes. No age-related changes in methylation pattern were detected. We can conclude therefore that the methylation pattern of the three X-linked genes is stable during aging in female leukocytes and that a high rate of age-related reactivation of X-linked genes may not be a feature of all X-linked loci.
Adolescent↗
NMR analysis of low-density lipoprotein oxidatively-modified in vitro.
Human plasma low density lipoprotein has been oxidized at different stages in vitro and analysed by 1H, 13C, and 31P NMR spectroscopy and by biochemical methods. Information was obtained on: a) structure mobilities of lipids and on lipid-protein interactions; b) conjugated and oxo-dienes; c) polyunsaturated/monounsaturated fatty acid chains; d) lysophosphatidylcholine production. The results show that the NMR approach is particularly useful for the assessment of structural modification in oxidized LDL.
Copper↗
Human apolipoprotein A-I gene promoter polymorphism: association with hyperalphalipoproteinemia.
An apolipoprotein A-I gene promoter polymorphism, due to an adenine (A) to guanine (G) transition 78 base pairs upstream from the transcription initiation site, was studied by amplification of the corresponding region of the apoA-I gene, DNA sequencing, and allele-specific oligonucleotide hybridization. The frequency of the polymorphism was studied on female and male individuals classified into three groups according to the high density lipoprotein (HDL) cholesterol concentration. The allelic frequencies for the A polymorphism were 0.10, 0.14, 0.27 in women and 0.08, 0.17, 0.14 in men in the lowest, in the intermediate (between 10th and 90th percentile), and the highest decile of HDL cholesterol levels, respectively. Statistical analysis showed a significant difference of allelic frequencies between the highest and the lowest deciles (P less than 0.006) and between the highest and the intermediate deciles of HDL cholesterol in women (P less than 0.04) but not in men. As the sequences surrounding the polymorphism are known to be involved in transcription modulation, it is possible that the A-G transition polymorphism may have an influence on apoA-I synthesis and, in consequence, on the HDL cholesterol levels in women.
Adult↗
Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia.
Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene.
Adult↗
Locally advanced lung cancer treatment: personal experience of 588 stage III operated on patients.
From 1967 to 1988, we operated on 1507 non-small cell lung cancer. Complete data concerning patients at stage III are available for 501 of them. In 73% of cases the histological type was epidermoid, in 22% it was adenocarcinoma and in 5% large cells anaplastic carcinoma. Explorative thoracotomy (E.T.) was performed in 45% of interventions whereas curative resections in 55%. Sixty-two percent of these patients underwent pneumonectomy and thirty-eight percent lobectomy. Exeresis interventions were performed in patients at stage III A in 86% of cases, whereas in patients at stage III B in 14% of cases. Five years survival rate for stage III non small cell lung cancer is 17% whereas in stage II is 33% and in stage I is 52%. The only valuable prognostic factor seems to be the size of parenchymal exeresis. Indeed, survival rate after lobectomy is 24% versus 13% after pneumonectomy. In our experience the different survival between tumours at stage III A and tumours at stage III B are not significant, when the unexpected intraoperative finding of marginal infiltration of mediastinal organ is still compatible with resection. Also the survival rates between the two histological types are not statistically significant.
Carcinoma, Non-Small-Cell Lung↗
Cytogenetic analysis in 28 radically operated non-small-cell lung cancer: preliminary considerations.
Twenty-eight radically operated non-small-cell lung cancer patients were analyzed with regard to chromosomal assessment and DNA content: in 13 cases, different quantitative/qualitative chromosome alterations were found. In particular, in 12 cases marker chromosomes and cytogenetic abnormalities in euploid cells were demonstrated. The prognostic value of these findings will be aim of further studies.
Aneuploidy↗
[Clinical significance of cell kinetics in lung cancer].
A series of 24 lung cancer cases was studied: 12 epidermoid carcinomas, 9 adenocarcinomas, 2 giant-cell carcinomas and 1 carcinoid. The patients were staged on the basis of the TNM classification system as 9 stage I, 5 stage II, 9 stage III and 1 stage IV. Using fresh tumour cell samples 2 cell cultures were prepared for each patient: one to identify the percentage of S phase cells (Labelling Index) using the tritiated thymidine method and one for cytogenetic analysis. A gentic map was obtained in 6 cases and revealed no specific numerical or structural alterations. The Labelling Index (L.I.) was calculated for all patients and compared with all TNM parameters. This revealed a certain connection between L.I. and parameters T, SN and G but no link with parameters.
Adenocarcinoma↗
Cholesteryl ester storage disease: risk factors for atherosclerosis in a 15-year-old boy.
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Adolescent↗
Characterization of genetic markers in the 3' end of the apo B gene and their use in family and population studies.
The 3' end of the apo B gene is highly polymorphic. Two point mutations in the coding sequence of the gene create EcoRI (E+, E-) and XbaI (X+, X-) RFLPs. The two loci are in random association and the frequency of the four haplotypes, E+X+, E+X-, E-X+ and E-X- in the normolipidaemic population are 0.68, 0.30, 0.02 and 0.00, respectively. Although the polymorphic nucleotide underlying the EcoRI RFLP creates an amino acid substitution in the apo B protein (Glu----Lys) in a region close to a putative LDL-receptor recognition site(s), we find no statistically significant difference in the frequency of the apo BGlu and apo BLys alleles in hyperlipidaemic patients (familial hypercholesterolaemia, type IIA with no tendon xanthomas, IIB and probably IV) and the normolipidaemic population. In contrast, we confirm previous findings, that the X+ allele is in linkage disequilibrium with a genetic locus that predisposes to the development of higher fasting plasma triglyceride levels than the X- allele. We have characterized a highly polymorphic region immediately 3' to the apo B gene. At least 5 alleles of this locus exist in the population and our family studies show it should be an extremely informative locus to use in studies where polymorphic or mutant apo B alleles are suspected to underly certain forms of familial hyperlipidaemia. DNA sequence analysis of this highly polymorphic locus shows that the variation is entirely attributable to the number of times the simple repeating sequence 5'-TTTATAATTAAAATATTTATAATTAAATAT-3' is present.
Adult↗
A study of the structure of the gene for lecithin: cholesterol acyltransferase in four unrelated individuals with familial lecithin: cholesterol acyltransferase deficiency.
1. We have used polyclonal antibodies and a complementary DNA clone for human lecithin:cholesterol acyltransferase (LCAT) to study LCAT protein and the structure of the LCAT gene, respectively, in patients with familial LCAT deficiency from Norway, Ireland, Germany and Italy. 2. The patients had low levels of non-functional LCAT protein in their serum as measured by rocket immunoelectrophoresis; its mol. wt. of approximately 68,000 was identical with that of LCAT in normal plasma, as judged by immunoblotting. 3. Enzymatic digestion of DNA samples from the patients produced LCAT gene fragments which were indistinguishable from those found in normal individuals. 4. We conclude that LCAT deficiency in these patients is not caused by a large deletion or rearrangement of the LCAT gene sequences.
Genes↗