RFLPs of the LDL-receptor gene: their use in the diagnosis of FH and in evaluation of different levels of gene expression on normal subjects.

The usefulness of the RFLPs of the LDL-receptor gene in early diagnosis of Familial Hypercholesterolemia (FH) was investigated in 122 FH-families. Four RFLPs, produced by digestion with the enzymes PvuII, ApaLI and AvaII/XbaI were able to detect the affected gene and to follow the inheritance of the disease in 72 out of 97 families (74%). In the remaining 25 families, unambiguous diagnosis was possible in 66% of the cases by use of PvuII, ApaLI and BstEII/EcoRI RFLPs. The RFLPs were also useful to distinguish true homozygotes from compound heterozygotes and to detect families where recombination events occurred or where hypercholesterolemia was not due to a defect of the LDL-receptor gene. In a normal population PvuII RFLP account for 9.6% of the total variance of the LDL cholesterol levels adjusted for confounding variables. The P2 allele was associated with lower LDL cholesterol concentrations (average excess -9.1 mg/dl). This finding allows us to presume there is a DNA sequence, close to the variable PvuII cutting site in intron 15, which could act as an enhancer of the LDL-receptor gene expression.

Variation in the low density lipoprotein receptor gene is associated with differences in plasma low density lipoprotein cholesterol levels in young and old normal individuals from Italy.

We have used four restriction fragment length polymorphisms (RFLPs) of the human low density lipoprotein receptor (LDL-R) gene, detected by the restriction enzymes Ava II, Pvu II, and ApaLI (5' and 3'), to study the effect of variation at this gene locus in determining plasma cholesterol and LDL cholesterol levels. Two hundred eighty-nine normolipidemic individuals were studied from the Liguria region of Italy. The Pvu II RFLP was significantly associated with differences in plasma total and LDL cholesterol levels, explaining 9.6% of the sample variance in LDL cholesterol levels. The other RFLPs, which are in strong linkage disequilibrium with the Pvu II RFLP, were associated with smaller effects on LDL cholesterol. The Pvu II allele, distinguished by the presence of the variable cutting site (P2 allele), was associated with lower levels of total and LDL cholesterol, and the frequency of the P2 allele was significantly reduced in individuals with LDL cholesterol levels higher than the 75th percentile. The frequency of the P2 allele was significantly higher in the group of individuals over 65 years old, and in this group the P2 allele was also associated with a similar reduction in LDL cholesterol levels. Because of linkage disequilibrium, only four RFLP haplotypes were common in this sample. Of these, only the haplotype P2A2VI (relative frequency, 0.269) was associated with a reduction in LDL cholesterol (average excess, -11.5 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

[Rheologic effects of salmon calcitonin on post-menopausal osteoporosis. Results of a preliminary study]. / Effetti reologici della calcitonina di salmone nell'osteoporosi post-menopausale. Risultati di uno studio preliminare.

The aim of this random blind vs placebo study was to assess the effect of salmon calcitonin (sCT) (100 UI/day intermuscular for 4 weeks) on the haemorheological pattern of 20 women, all non-smokers, aged between 50 and 65 years of age and affected by post-menopausal osteoporosis. Hematocrit, whole blood viscosity at high and low shear rates, plasma viscosity, red blood cell aggregation, dynamic deformation and viscosity were monitored. Our results show sCT ex vivo seems to act upon mechanisms regulating the plastic properties of the red blood cell membrane.

[Visualization of carotid and femoral atherosclerotic lesions using autologous lipoprotein reinjection containing apo-B marked with 131I: preliminary data]. / Visualizzazione delle lesioni aterosclerotiche del distretto carotideo e femorale mediante reiniezione di lipoproteine autologhe contenenti apo-B marcate con 131I: dati preliminari.

Atherosclerotic lesions can be detected by several methods, such as angiography, B-mode ultrasonography, computed tomography and magnetic resonance. Radioisotopic techniques, recently introduced by using radiolabelled platelets and LDL (low-density lipoproteins), can give more informations about the "metabolic activity" of atherosclerotic lesions. The aim of this study was to detect atherosclerotic lesions in 7 hyperlipemic patients using autologous apo-B containing lipoproteins labelled with 131I in order to evaluate different functional patterns of these lesions. Carotid and femoral accumulations of this radiocompound were detected in the majority of patients. The method appears promising for evaluating the "in vivo" relationships between lipoproteins, which are involved in the pathogenesis of atherosclerosis, and the vessel wall.

Correlation between hemorheologic parameters and carotid atherosclerosis in stroke.

An evaluation of the hemorheologic parameters and an ultrasonographic study of the extracranial carotid tract were performed on 48 patients, age range: sixty to seventy-five years, affected by acute stroke, 23 of whom had hypertension, while 27 were smokers. None of them was suffering from hyperlipidemia, diabetes mellitus, or symptomatic coronary heart or peripheral artery disease. The echotomographic analysis, using B-mode real-time echotomography revealed atherosclerotic lesions in 26 patients. The hemorheologic pattern (hematocrit, fibrinogen, whole blood filterability, whole blood and plasma viscosity) was determined in all the patients three months after the clinical event. Statistical analysis of the results indicates a possible link between atherosclerotic lesions of the extracranial carotid tract and age, fibrinogen levels, and whole blood filterability.