Pyrazolo[1,5-a]-1,3,5-triazine C-nucleoside as deoxyadenosine analogue: synthesis, pairing, and resistance to hydrolysis.

The synthesis of a pyrazolo[1,5-a]-1,3,5-triazine C-nucleoside (dA(PT)), designed to form two hydrogen bonds with a complementary dT residue, is reported. Oligonucleotides including this dA nucleoside analogue possess base-pairing properties similar to those of the parent oligonucleotide. This dA nucleoside analogue is more resistant to acid-catalyzed hydrolysis than dA.

Synthesis and properties of 2'-O-neopentyl modified oligonucleotides.

2'-O-Neopentyldeoxyuridine (Un) was synthesized and incorporated into a series of oligodeoxyribonucleotides. Single and triple incorporations in various arrangements were performed. The Watson and Crick pairing properties with complementary DNA and RNA were investigated by UV melting curves, CD spectroscopy, and molecular dynamic simulations.

A novel strategy for human papillomavirus detection and genotyping with SybrGreen and molecular beacon polymerase chain reaction.

Human papillomaviruses (HPVs) play an important role in the pathogenesis of cervical cancer. For identification of the large number of different HPV types found in (pre)malignant lesions, a robust methodology is needed that combines general HPV detection with HPV genotyping. We have developed for formaldehyde-fixed samples a strategy that, in a homogeneous, real-time fluorescence polymerase chain reaction (PCR)-based assay, accomplishes general HPV detection by SybrGreen reporting of HPV-DNA amplicons, and genotyping of seven prevalent HPV types (HPV-6, -11, -16, -18, -31, -33, -45) by real-time molecular beacon PCR.

Linear 2' O-Methyl RNA probes for the visualization of RNA in living cells.

U1snRNA, U3snRNA, 28 S ribosomal RNA, poly(A) RNA and a specific messenger RNA were visualized in living cells with microinjected fluorochrome-labeled 2' O-Methyl oligoribonucleotides (2' OMe RNA). Antisense 2' OMe RNA probes showed fast hybridization kinetics, whereas conventional oligodeoxyribonucleotide (DNA) probes did not. The nuclear distributions of the signals in living cells were similar to those found in fixed cells, indicating specific hybridization.

Simultaneous A8344G heteroplasmy and mitochondrial DNA copy number quantification in myoclonus epilepsy and ragged-red fibers (MERRF) syndrome by a multiplex molecular beacon based real-time fluorescence PCR.

The association of a particular mitochondrial DNA (mtDNA) mutation with different clinical phenotypes is a well-known feature of mitochondrial diseases. A simple genotype-phenotype correlation has not been found between mutation load and disease expression. Tissue and intercellular mosaicism as well as mtDNA copy number are thought to be responsible for the different clinical phenotypes.

Effect of pravastatin, a HMG CoA reductase inhibitor, on blood lipids and aortic lipidosis in cholesterol-fed White Carneau pigeons.

The effect of pravastatin, an inhibitor of HMG CoA reductase, on blood lipids and aortic lipidosis was studied in young cholesterol-fed White Carneau pigeons. The birds were fed with normal ('N group', n = 20) or atherogenic diet (grains + 0.4% cholesterol + 4% lard) alone ('C group', n = 20) and in association with pravastatin ('P group', n = 20).

Relationship between smoking status and serum lipids in a hyperlipidemic population and analysis of possible confounding factors.

The aim of our study was to estimate the potential relationship between smoking behavior and other coronary heart disease risk factors in 250 hyperlipidemic patients. We present data obtained through self-reporting of the number of cigarettes smoked per day, measurements of three tobacco markers, and data on dietary habits and lipid variables. We measured cotinine (by HPLC) and thiocyanate and used a recent colorimetric assay for the indirect evaluation of the nicotine metabolites in a single urine specimen.

Carotid stenosis is a powerful predictor of a positive exercise electrocardiogram in a large hyperlipidemic population.

Hypercholesterolemia is a major risk factor in coronary heart disease (CHD) and ischemic stroke. However, there is no general agreement on the usefulness of systematic screening of patients with hyperlipidemia by stress exercise electrocardiogram (ECG). The feasibility of this approach would depend on selecting patients with a high risk of CHD, since the sensitivity and specificity of the test depends on the prevalence of the disease.

Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method.

To investigate the molecular basis of familial hypercholesterolemia (FH) in France, we applied the single strand conformation polymorphism (SSCP) method to the promoter region and the 18 exons of the low density lipoprotein receptor (LDLR) gene. Seven probands, 4 heterozygotes, 2 compound heterozygotes, and 1 homozygote, belonging to FH families were tested. In all cases, previous genetic analysis and/or LDL receptor fibroblast assay had shown that the disease was due to defects in the LDLR gene.

[Comparison about the efficacy and tolerability between simvastatin and bezafibrate in the treatment of hypercholesterolemia].

Simvastatin and bezafibrate actions on blood lipids and their side effects were compared in a double-blind trial involving 24 adults with severe type IIa or IIb primary hypercholesterolemia (mean plasma cholesterol = 4.35 g/l). During a 12-week period, the patients received either bezafibrate, 600 mg 3 times a day, or simvastatin, 10 or 20 mg once a day, with a doubling of the dosage at week 6 if the LDL-cholesterol level remained above 1.

Lp(a) levels in different types of dyslipidemia in the French population.

The serum lipoprotein Lp(a) concentration was measured in 1065 individuals in order to assess whether there was a relation between the type of dyslipidemia and the level of Lp(a). Males and females, aged between 2 and 83 years old, were included in the study. Quantification was performed by an immunonephelometric technique.

An initiation codon mutation in the apoC-II gene (apoC-II Paris) of a patient with a deficiency of apolipoprotein C-II.

We have identified the genetic defect that leads to a deficiency of apoC-II in the proband from the Paris kindred. Analysis of the apoC-IIParis DNA by Southern blot hybridization revealed no major gene rearrangements, but sequencing of polymerase chain reaction-amplified apoC-IIParis DNA revealed an A to G transition that changed the initiation AUG (methionine) codon to GUG (valine). Potential initiation of translation at the closest inframe methionine codon eliminates the entire signal peptide and the first 8 amino-terminal residues of apoC-II which would prevent apoC-II secretion into plasma.

[Lipoprotein Lp(a): a new risk factor of atherogenesis].

Lp(a) is a lipoprotein present in all individuals in concentrations that are genetically determined. Its structure is characterized by the presence of an apoprotein with a high carbohydrate content called apoprotein a. Since 1972, numerous concordant data have endowed Lp(a) with a high risk of atherogenesis.

Coagulation factor VII and plasma triglycerides. Decreased catabolism as a possible mechanism of factor VII hyperactivity.

High circulating levels of coagulation factor VII (FVII) are known to be associated with elevated concentrations of blood lipids. More specifically, hypertriglyceridemia is correlated with raised FVII coagulant activity (FVIIc). Recently, evidence has been described which suggests that elevation in FVIIc might reflect an increase in the total concentration of FVII, as evaluated by quantitation of FVII antigen (FVIIag).

Plasma factor VII, triglyceride concentration and fibrin degradation products in primary hyperlipidemia: a clinical and laboratory study.

There is evidence that the increase in coagulation factor VII (FVII) represents a predictive risk factor of arterial thrombosis in coronary heart disease. Its relative contribution to this multifactorial process and its relationship to other risk factors, namely cholesterol and triglycerides, is yet a matter of investigation. In this study we aimed to clarify whether FVII synthesis or activation correlated with plasma lipid concentrations.

[Comparison between treatments of severe forms of familial hypercholesterolemia by total plasma exchange and selective removal of low density lipoproteins (LDLapheresis)].

A plasma exchange program for familial hypercholesterolaemia was started in 1982. Ten patients aged from 7 to 58 years were progressively included: 3 had an heterozygous form of the disease with ischaemic heart disease; 3 had an homozygous form with defective low density lipoprotein receptor activity, 4 had a receptor-negative homozygous familial hypercholesterolaemia and had previously undergone portacaval shunt. During total plasma exchange against human albumin (470 sessions in 9 patients) low density lipoprotein cholesterol values, but also high density lipoprotein cholesterol values, decreased by 40 per cent.

[Van Bogaert's cerebrotendinous xanthomatosis. A study of 3 cases].

The authors report three observations of cerebro-tendinous xanthomatosis (CTX). The three patients presented tendinous xanthoma and cataract. The neurologic disorders were different in each case.

Bartter's syndrome with normal chloride reabsorption during indomethacin treatment.

A 17-year-old male patient with Bartter's syndrome was admitted for renal function studies. This patient had persistent hypokalemia, first found at age 5; the diagnosis of Bartter's syndrome with renal hypersecretion of prostaglandins E2 and F2 alpha had been established at age 13. A congenital defect of chloride reabsorption was expected, but after 4 years of indomethacin treatment no such defect was found.

Direct fetal blood examination for prenatal diagnosis of homozygous familial hypercholesterolemia.

Prenatal diagnosis of homozygous hypercholesterolemia was achieved at the 24th week of gestation by analysis of lipid values in a fetal blood sample obtained by a needle guided by ultrasound. These abnormal values were compared to values in blood obtained from normal fetuses at the same stage of gestation. After abortion, the diagnosis was confirmed by measuring LDL receptor activity on fibroblast cultures from a skin biopsy.