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Biomedical subjects

F Basso

Publications and source records attributed to F Basso.

10 recordsLinked to original sources

Combined segregation and linkage analysis of fibrinogen variability in Israeli families: evidence for two quantitative-trait loci, one of which is linked to a functional variant (-58G > A) in the promoter of the alpha-fibrinogen gene.

The association of alpha- and beta-fibrinogen polymorphisms with plasma fibrinogen levels was examined in a sample of 452 family members from 80 Israeli kindreds. The measured genotype analysis indicated that the beta-fibrinogen -455G > A polymorphism was not associated with fibrinogen levels, while the alpha-fibrinogen -58G > A locus showed a significant association with fibrinogen levels (chi2= 17.7; df = 3; p < 0.001), with the -58A allele being associated with higher levels. Segregation analysis in this sample suggested a recessive quantitative-trait locus (QTL) with a major effect that controlled the sex- and age-adjusted fibrinogen levels. Results from a combined segregation/linkage analysis indicated that a single QTL influencing plasma fibrinogen is in gametic equilibrium with the beta-fibrinogen -455G > A and alpha-fibrinogen -58G > A polymorphisms. An extended analysis with a two-QTL model significantly improved the fit of the model (p < or = 0.001), and gave support for linkage between the fibrinogen QTL and the alpha-fibrinogen polymorphism. In vitro analysis with a DNA fragment containing this variant, linked to a reporter gene, showed 2-fold higher expression of the A allele compared to the G allele in the liver cell line HepG2, both under basal conditions and after stimulation with interleukin 6. These results demonstrate that two QTLs are jointly involved in determining plasma fibrinogen levels in this sample of families, one of which is located close to a functional variant in the alpha-fibrinogen locus.

Cell Line↗

A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease.

AIMS: The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study. METHODS: One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms, -670A-->C, -402G-->A, a 10 base pair insertion at -323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays. RESULTS: The -670A-->C and -402G-->A polymorphisms were in complete allelic association. The haplotype containing -670C and -402A (frequency =0.23) was associated with significantly increased plasma FVII coagulant activity and increased risk of an initial coronary event, particularly acute myocardial infarction, which remained after correction for conventional risk factors. In contrast, the -323 insertion and Q353 alleles (frequency =0.11 and 0.10, respectively) were associated with decreased plasma FVII levels, but hazard ratios for coronary events in carriers of these alleles were not significantly different from unity. In transiently transfected hepatoma cells, increased basal expression of the reporter gene was directed by a promoter fragment with rare haplotype -670C/-630G/-402A rather than by a promoter fragment with common haplotype -670A/-630A/-402G; -402A was not responsible for this effect. CONCLUSIONS: The promoter haplotype, -670C/-630G/402A, was associated with significantly increased plasma FVII coagulant activity, risk of an initial coronary event, particularly acute myocardial infarction, and reporter gene expression.

Alleles↗

Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages.

Atherogenesis involves several aspects of chronic inflammation and wound healing. Indeed, the atheroma is considered a special case of tissue response to injury. Injurious stimuli may include lipoproteins trapped within lesions where protein and lipid moieties have undergone chemical modifications. We have studied the effect of oxidized low density lipoproteins (ox-LDL) on inducible cyclooxygenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide (LPS). Levels of both Cox-2 and constitutive cyclooxygenase (Cox-1) were assessed using Western blot analysis. Prior incubation of macrophages with ox-LDL resulted in a strong inhibition of Cox-2 induced by LPS, without effect on Cox-1. The inhibitory effect was dependent on ox-LDL concentration and its onset was early in time (already detectable 1 hour after macrophage exposure to ox-LDL). Native LDL, and other forms of modified LDL, were without effect. The inhibition was dependent on endocytosis of ox-LDL and could be reproduced using the lipid extract from ox-LDL. Lysophosphatidylcholine, 7beta-hydroxycholesterol, and 7-oxocholesterol failed to mimic the inhibition, but oxidized arachidonic acid-containing phospholipids, produced by autoxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, markedly inhibited Cox-2. The observation that ox-LDL downregulates Cox-2 in human macrophages may explain the fact that, within atheromata, the transformation of macrophages into foam cells results in attenuation of the inflammatory response, thus contributing to progression of atherogenesis.

Cells, Cultured↗

Characterization of Bordetella pertussis strains of recent isolation.

During the clinical trial conducted in Italy to evaluate the efficacy of new acellular pertussis vaccines, the most favorable conditions for the recovery and characterization of Bordetella pertussis strains, isolated from children with cough, were adopted. The nasopharyngeal aspirates were collected and sent to the laboratory in refrigerated conditions within 24 hours. Charcoal agar selective and non selective plates were used, and most of the isolates were recovered after 3-4 days of incubation. Confirmation of all suspected colonies included the use of biochemical tests and specific agglutination reaction with B. pertussis antiserum. Serotyping of fimbriae, susceptibility to erythromycin and DNA fingerprinting by Pulsed Field Gel Electrophoresis (PFGE), were performed to characterize B. pertussis isolates and to determine relatedness among different strains. Serotype 1,3 was the most represented in the bacterial population examined. A predominant pulsetype (PTA) characterized most of the isolates accounting for 71.4% of the strains examined. Eight subclones (23.5%) and three unrelated pulsetypes were also found. No resistant strains to erythromycin were detected.

Bacterial Typing Techniques↗

Antibody kinetics and long-term sero-prevalence in the Italian clinical trial of acellular pertussis vaccines.

In the Italian Pertussis Vaccine Trial, data were collected to evaluate the persistence of anti-pertussis antibodies. A sub-cohort of 1275 children was followed for this purpose until a mean age of 21 months. An additional evaluation included pooled cross-sectional analysis of serum specimens collected for analysis of cough illnesses. Antibodies to PT, FHA and PRN were measured by ELISA using a standardized technique. With both acellular vaccines in the study (the Chiron Biocine three-component and SmithKline Beecham three-component vaccines) there was a fast and steep decrease of mean geometric titres for PT, FHA and PRN in the months immediately following vaccination. Titres were close to the detection limit 15 months after the end of primary immunization. The immunogenicity of the whole-cell study vaccine (produced by Connaught Laboratories, Inc. Swiftwater, USA) was poor as determined one month after the third dose and no antibody was detected in nearly all children 15 months after the end of vaccination.

Adhesins, Bacterial↗

Comparison of Laparoscopic versus Conventional Treatment of Ovarian Endometrioma

An observational prospective cohort study was conducted with a historical control group and 140 infertile women with the laparoscopic diagnosis of ovarian endometrioma over 1 cm diameter. The groups were comparable regarding age, duration of infertility, and disease severity. All patients had a follow-up of 12 months after treatment, and at least one patent tube. The laparoscopic group (group A) consisted of 46 woman, 35 of whom received suppressive treatment with danazol, Gestinone, or leuprolide acetate for 4 to 6 months. In the control group (group B), 94 women underwent diagnostic laparoscopy plus 6 months of danazol or Gestinone therapy. After 3 months, microsurgery by laparotomy was performed. During the follow-up, period 24 pregnancies were achieved in group A (52%) and 58 in group B (61%, chi2 0.796). Fifteen (48%) of 31 women with cysts 1 to 3 cm in group A conceived, as did 52 (62%) of 81 in group B. Nine (60%) of the 15 with cysts over 3 cm in group A, and 7 (58%) of 12 in group B conceived. No significant difference was found among the suppressive drugs in either group. Only 4 (36%) of the 11 women in group A not receiving suppressive treatment became pregnant. No significant difference (p >0.05) was found when comparing the combined treatment group (57%). According to the revised classification of endometriosis, 18 (51%) of 35 pregnancies were achieved in women with moderate disease in group A and 41 (64%) of 64 in group B. In those with severe disease, 6 (55%) of 11 became pregnant in group A and 17 (57%) of 30 in group B. There was no significant difference between the groups when comparing global results, ovarian endometrioma size, medical treatment, and severity of endometriosis. Given comparable surgical expertise, operative laparoscopy should be the procedure of choice in the treatment of ovarian endometrioma whenever possible, due to its recognized advantages.

Journal Article↗

Adherence of Borrelia burgdorferi and Borrelia hermsii to mammalian cells in vitro.

This study investigated the ability of Borrelia burgdorferi and Borrelia hermsii to attach the surface of several types of in vitro-cultured mammalian cells. Borreliae showed different adhesion efficiencies depending on cell type and temperature. Temperatures both lower and higher than 33 degrees and 37 degrees C respectively, decreased the adhesion of borreliae which preferentially adhere to human fibroblast-like cells. The adhesion process, mediated by structures exposed onto the surface of the microorganisms, also proved to be sensitive to the treatment of mammalian cells with hyaluronidase and sialidase, confirming that carbohydrate receptors are involved in the adhesion of borreliae to eukaryotic cells.

Animals↗

Amitriptyline-related peripheral neuropathy. Case report.

Although amitriptyline is not usually regarded as toxic to the peripheral nervous system (PNS) and is even prescribed by some for neuropathic pain, there are sporadic reports of peripheral neuropathy following overdose or prolonged use of the drug. The scarcity of data leads us to report a case we have followed for 3 years clinically and electromyographically. A 54 year old man on oral amitriptyline 150 mg uninterruptedly for 2 years consulted us for lower limb paresthesias and was found on clinical examination to have reduced ankle jerks and mild distal global hypoesthesia. EMG yielded a pattern of sensorimotor neuropathy compatible with axonal disease in all four limbs. The history was unremarkable and the laboratory data were within normal limits. After discontinuation of amitriptyline therapy both the clinical and EMG pattern gradually normalized. We draw attention to the possible risk, infrequent though it is, of PNS neurotoxicity of a widely used drug reputedly harmless from this point of view.

Amitriptyline↗