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C Vergani

Publications and source records attributed to C Vergani.

At least 73 records · Page 4Linked to original sources
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

Radiotherapy versus radiotherapy plus cisplatin treatment for locally advanced non small cell lung cancer: preliminary results of a randomized study.

Preliminary results of a randomized study (radiotherapy versus radiotherapy plus weekly low-dose cisplatin) are reported. Fifty-four patients (43 evaluable) with stage IIIa-b non small cell lung cancer were randomized. Objective responses (CR + PR) were seen in 62% of the radiotherapy-treated group and in 63% of the group treated with radiotherapy plus cisplatin. No major toxicity was seen. Patient compliance for both treatments was satisfactory.

Adult↗
PubMed1987

[Current status of the use of vitamins (A, E, C, D), folates and selenium in the chemoprevention and treatment of malignant tumors].

The role of vitamins A, E, C, D, folates and selenium in the chemical prevention of tumours and/or precancerous conditions is examined in the light of epidemiological studies and experimental observations. Particular mention is made of significant clinical studies that provide valuable indications about the use of vitamin A and its derivates in particular for the treatment of precancerous and cancerous conditions. Vitamin A and its derivates apparently play a fundamental role not only in the treatment of proliferating malignancies of the skin (carcinomas, severe aclinic keratosis) or involving the skin (fungoid mycosis, skin metastases of solid tumours) but also in the prevention of recurring bladder tumours and the treatment of several bronchial dysplasias.

Ascorbic Acid↗
PubMed1986

Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia.

Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic. The absence and presence of this site, as determined by genomic blotting analysis of PstI-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe, were associated with 3.3-kb and 2.2-kb hybridization bands, respectively. The 3.3-kb band appeared in 4.1 percent of 123 randomly selected control subjects and in 3.3 percent of 30 subjects with no angiographic evidence of coronary artery disease. In contrast, among 88 patients who had severe coronary disease before the age of 60, as documented by angiography, the 3.3-kb band occurred in 32 percent (P less than 0.0001). It was also found in 8 of 12 index cases (P less than 0.0001) of kindreds with familial hypoalphalipoproteinemia. In the two patient groups, the allele frequencies of the site that produced the 3.3-kb band were 17 and 42 percent, respectively, as compared with an allele frequency of only 2 percent in the control populations. Within kindreds with familial hypoalphalipoproteinemia and among first-degree relatives of patients with coronary artery disease, the 3.3-kb band was associated with decreased HDL cholesterol levels. Among all patients with coronary artery disease, 58 percent had HDL cholesterol levels below the 10th percentile of normal values; however, this frequency increased to 73 percent when patients with the 3.3-kb band were considered. These findings indicate that the polymorphism in the region between the apolipoprotein A-I and apolipoprotein C-III genes may be a useful marker for the risk of premature coronary artery disease and familial hypoalphalipoproteinemia.

Age Factors↗