Search PubMed⌕ Search

Biomedical subjects

F Rousseau

Publications and source records attributed to F Rousseau.

At least 73 records · Page 4Linked to original sources
PubMed1995

Screening for Down syndrome during the first and second trimesters: impact of risk estimation parameters.

OBJECTIVES: To evaluate impact of risk estimation parameters for screening for Down Syndrome during the first and second trimesters. METHODS: We prospectively examined for their performance in the prenatal prediction of trisomy 21, alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic gonadotropin (hCG), and its free subunits (free alpha-hCG, free beta-hCG) at both the first and second trimesters, and the impact of three sets of published risk estimation parameters. A total of 14,612 pregnancies were studied. All Down syndrome specimens (12 and 11 cases for first and second trimesters, respectively) and a sample of the unaffected pregnancies were analyzed. RESULTS: The median multiple of median (MoM) for total hCG was lower in the first trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative power was observed if the lower variability of the results in the first trimester is taken into account (interquartile range of 0.251 vs. 0.338). The choice of distribution parameters did not alter significantly the detection rates for the various combinations of markers (p > 0.05). False positive rates were affected significantly however and for the combination AFP-uE3-free beta-hCG they varied from 14.6% to 22.6% (p < 0.001). CONCLUSIONS: Our results suggest that specific distribution parameters would be necessary to account for the lower variability of the markers in the first trimester and the peculiarity of the total hCG assay we used.

Adult↗
PubMed1995

Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients.

The fragile X syndrome is the most frequent cause of inherited mental retardation. The molecular mechanism of the disorder is based on the expansion of a CGG repeat in the 5' UTR of the FMR1 gene in the majority of fragile X patients. The instability of this CGG repeat containing region is not restricted to the CGG repeat itself but expands to the flanking region as well. We describe four unrelated fragile X patients that are mosaic for both a full mutation and a small deletion in the CGG repeat containing region. Sequence analysis of the regions surrounding the deletions showed that both the (CGG)n repeat and some flanking sequences were missing in all four patients. The 5' breakpoints of the deletions were found to be located between 75-53 bp proximal to the CGG repeat. This suggests the presence of a hot spot region for deletions in the CGG repeat region of the FMR1 gene and emphasizes the instability of this region in the presence of an expanded CGG repeat.

Base Sequence↗
PubMed1995

A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture.

The fragile X syndrome is an X-linked inherited disease and is the result of transcriptional inactivation of the FMR1 gene and the absence of its encoded FMR protein (FMRP). Using a specific monoclonal antibody directed against human FMRP, we have studied the steady-state levels of its murine homolog in several tissues and organs of adult and young mice. In immunoblot analyses, the antibody recognizes a heterogeneous subset of proteins with apparent molecular weights ranging from 80 to 70 kDa. These proteins are detected in all the 27 tissues tested; however, the relative proportion of each polypeptide recognized varies between tissues, and a significantly higher expression is observed in young animals. Northern blot analysis of RNA extracted from selected tissues from adult mouse shows that these tissues express the major 4.8 kb mRNA, although at different levels, and contain several additional shorter transcripts, particularly in muscular tissues. We also report that expression of the FMR1 gene is modulated in proliferating and quiescent primary mouse kidney cell cultures with an inverse relationship between levels of FMR1 mRNA and of its encoded proteins. This suggests that FMRPs are highly stable in quiescent cells and that FMR1 expression is likely post-transcriptionally controlled. Our results document the widespread expression of the FMR1 gene, and suggest that it is controlled by different mechanisms implicated in cell growth and differentiation.

Animals↗
PubMed1995

Zero effect of crowding on arousal and performance: on 'proving' the null hypothesis.

This study examined the effect of crowded versus uncrowded conditions upon pulse and self-rated arousal, and upon verbal production performance in subjects' first and second languages. Participants were 52 francophone college students. Arousal estimates were identical for crowded and noncrowded conditions as was verbal performance, thereby contradicting the theories of Zajonc (1965) and Freedman and Perlick (1979) in which crowding is viewed as an activating and intensifying stimulus. Crowding itself appears to have no direct effect on arousal or behaviour as measured.

Adolescent↗
PubMed1995

Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome.

The fragile X syndrome is the second leading cause of mental retardation after Down syndrome. Fragile X premutations are not associated with any clinical phenotype but are at high risk of expanding to full mutations causing the disease when they are transmitted by a carrier woman. There is no reliable estimate of the prevalence of women who are carriers of fragile X premutations. We have screened 10,624 unselected women by Southern blot for the presence of FMR1 premutation alleles and have confirmed their size by PCR analysis. We found 41 carriers of alleles with 55-101 CGG repeats, a prevalence of 1/259 women (95% confidence interval 1/373-1/198). Thirty percent of these alleles carry an inferred haplotype that corresponds to the most frequent haplotype found in fragile X males and may indeed constitute premutations associated with a significant risk of expansion on transmission by carrier women. We identified another inferred haplotype that is rare in both normal and fragile X chromosomes but that is present on 13 (57%) of 23 chromosomes carrying FMR1 alleles with 53-64 CGG repeats. This suggests either (1) that this haplotype may be stable or (2) that the associated premutation-size alleles have not yet reached equilibrium in this population and that the incidence of fragile X syndrome may increase in the future.

Alleles↗
PubMed1994

Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.

Achondroplasia, the most common cause of chondrodysplasia in man (1 in 15,000 live births), is a condition of unknown origin characterized by short-limbed dwarfism and macrocephaly. More than 90% of cases are sporadic and there is an increased paternal age at the time of conception of affected individuals, suggesting that de novo mutations are of paternal origin. Affected individuals are fertile and achondroplasia is transmitted as a fully penetrant autosomal dominant trait, accounting for rare familial forms of the disease (10%). In contrast, homozygous achondroplasia is usually lethal in the neonatal period and affects 25% of the offspring of matings between heterozygous achondroplasia parents. The gene responsible for achondroplasia has been mapped to chromosome 4p16.3 (refs 7, 8); the genetic interval encompassing the disease gene contains a member of the fibroblast-growth-factor receptor (FGFR3) family which is expressed in articular chondrocytes. Here we report the finding of recurrent missense mutations in a CpG doublet of the transmembrane domain of the FGFR3 protein (glycine substituted with arginine at residue 380, G380R) in 17 sporadic cases and 6 unrelated familial forms of achondroplasia. We show that the mutant genotype segregates with the disease in these families. Thus it appears that recurrent mutations of a single amino acid in the transmembrane domain of the FGFR3 protein account for all cases (23/23) of achondroplasia in our series.

Achondroplasia↗
PubMed1994

High throughput and economical mutation detection and RFLP analysis using a minimethod for DNA preparation from whole blood and acrylamide gel electrophoresis.

We report a simple, rapid, and high throughput method which allows the simultaneous processing of multiple whole blood samples for routine DNA purification and analysis. The method is based on a microscale DNA preparation and digestion using minimal amounts of reagents and handling. The amount of material necessary for a Southern blot analysis (5-7 micrograms) is obtained from 200 microliters of whole blood. All steps involved in DNA preparation and restriction digestion are processed in a single 1.5-ml Eppendorf tube. DNA preparation is performed using a salting out procedure with a proteinase K digestion step but no phenol/chloroform extraction. Restricted fragments are separated by electrophoresis through polyacrylamide slab gels followed by electrotransfer to nylon membranes. By varying the electrophoresis parameters (V/cm or duration), fragments of interest up to 12 kb length can be separated with high resolution. At least 80 samples can be processed at once per DNA preparation, and multiples of this number depend on the available equipment. This economical and rapid method allows routine DNA analysis for mutation or RFLP detection to be performed on a large scale which is a mandatory feature in any DNA-based population screening program. In addition, the DNA purified by the minimethod can be used as an economical source for PCR analysis.

Blotting, Southern↗
PubMed1994

A gene for achondroplasia-hypochondroplasia maps to chromosome 4p.

Achondroplasia (ACH) is a frequent condition of unknown origin characterized by short-limbed dwarfism and macrocephaly. Milder forms, termed hypochondroplasias (HCH) result in short stature with radiological features similar to those observed in ACH. We report on the mapping of a gene causing ACH/HCH to human chromosome 4p16.3, by linkage to the iduronidase A (IDUA) locus, in 15 informative families (Z max = 3.01 at theta = 0 for ACH; Z max = 4.71 at theta = 0 for ACH/HCH). Multipoint linkage analysis provides evidence for mapping the disease locus telomeric to D4S412 (location score in log 10 = 4.60). Moreover, this study supports the view that ACH and HCH are genetically homogeneous in our series.

Achondroplasia↗
PubMed1994

No mental retardation in a man with 40% abnormal methylation at the FMR-1 locus and transmission of sperm cell mutations as premutations.

We report the case of a mentally normal male carrier of a fragile X full mutation with a 'methylation mosaic' hybridization pattern, who carried premutation-size mutations in his sperm cells and transmitted one of them to a daughter. Clinical evaluation of the father revealed a phenotype resembling that of the fragile X syndrome but without mental impairment and 4% fragile sites on cytogenetic analysis. Direct FRAXA genotyping revealed 40% abnormal methylation at the classical EagI FMR-1 restriction site, a delta of 400 bp to 1400 bp associated, in the non-methylated region, to a widely spread smear. This is thus a rare occurrence of a male carrier of a fragile X full mutation with significant methylation of the EagI site and no mental impairment. A premutation of 400 bp was detected in his daughter's leukocytes and analysis of sperm cells from the father revealed a normal spermogram and only 400 bp premutations. This is the first documented case of transmission (with analysis of sperm DNA) of a fragile X mutation from a male carrier of a full fragile X mutation to a girl. This may be due to the early setting apart of progenitor germ cells in males having inherited a premutation from their mother. It is more likely that there could be a strong selection process favouring those cells with a reverted full mutation which produced a small and unmethylated FMR-1 CpG island allowing for re-expression of the FMR-1 gene, especially in male germ cells.

Adult↗
PubMed1994

The fragile X syndrome: implications of molecular genetics for the clinical syndrome.

The fragile X syndrome of mental retardation is one of the most common genetic diseases. Characterization of the mutations involved has greatly improved our knowledge of the transmission of fragile X syndrome and new DNA-based diagnostics tools significantly outperform cytogenetic testing both for establishing the diagnosis and for determining carrier status. Fragile X mutations consist of an expansion of a CGG trinucleotide repeat localized in a gene (FMR-1) that is abnormally methylated in all affected individuals. They are classified as premutations (asymptomatic) and full mutations (associated with the disease). Several different DNA analysis protocols are used for fragile X genotyping but only a few have been tested on large samples of individuals. There are several clinical indications for direct DNA genotyping for fragile X including mental retardation, learning disability or hyperactivity in children with or without a family history of mental retardation, the establishment of carrier diagnosis in fragile X families and prenatal screening of children from carrier women.

Child↗
PubMed1994

A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases.

We report the results of a 14-center collaborative study of genotype-phenotype correlations in 318 fragile X families; these families comprised 2,253 individuals, 1,344 of whom carried a fragile X mutation and 693 of whom had a typical full fragile X mutation. This study demonstrates that direct DNA diagnosis establishes the genotype at the FRAXA-FMR-1 locus. There was a significantly higher prevalence of "mosaic" cases among males who carry a full mutation (12%) than among females who carry a full mutation (6%); the mosaic males had a larger expansion than did the mosaic females. Mental status of premutated individuals did not differ from that of those with a normal genotype. Both the abnormal methylation of the FMR-1-EagI site and the size of the expansion were highly correlated with cytogenetics, facial dysmorphism, macroorchidism, and mental retardation (MR). Among female carriers of a full mutation, those with MR had significantly larger expansion than did those without MR. Among 164 independent couples, 3 unrelated husbands carried a premutation that suggests that the prevalence of fragile X premutations in the general population is approximately 0.9% of the X chromosomes. Our data validate the use of direct DNA testing for fragile X diagnosis as well as for carrier identification and support and complete the established relationships among the DNA results and the cytogenetic, physical, and psychological aspects of the disease.

Adolescent↗
PubMed1993

Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion.

Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.

Adult↗
PubMed1993

Evidence for the involvement of PSI-E subunit in the reduction of ferredoxin by photosystem I.

Of the stroma-accessible proteins of photosystem I (PSI) from Synechocystis sp. PCC 6803, the PSI-C, PSI-D and PSI-E subunits have already been characterized, and the corresponding genes isolated. PCR amplification and cassette mutagenesis were used in this work to delete the psaE gene. PSI particles were isolated from this mutant, which lacks subunit PSI-E, and the direct photoreduction of ferredoxin was investigated by flash absorption spectroscopy. The second order rate constant for reduction of ferredoxin by wild type PSI was estimated to be approximately 10(9) M-1s-1. Relative to the wild type, PSI lacking PSI-E exhibited a rate of ferredoxin reduction decreased by a factor of at least 25. After reassociation of the purified PSI-E polypeptide, the original rate of electron transfer was recovered. When a similar reconstitution was performed with a PSI-E polypeptide from spinach, an intermediate rate of reduction was observed. Membrane labeling of the native PSI with fluorescein isothiocyanate allowed the isolation of a fluorescent PSI-E subunit. Peptide analysis showed that some residues following the N-terminal sequence were labeled and thus probably accessible to the stroma, whereas both N- and C-terminal ends were probably buried in the photosystem I complex. Site-directed mutagenesis based on these observations confirmed that important changes in either of the two terminal sequences of the polypeptide impaired its correct integration in PSI, leading to phenotypes identical to the deleted mutant. Less drastic modifications in the predicted stroma exposed sequences did not impair PSI-E integration, and the ferredoxin photoreduction was not significantly affected. All these results lead us to propose a structural role for PSI-E in the correct organization of the site involved in ferredoxin photoreduction.

Amino Acid Sequence↗
PubMed1993

Prolonged and fatal disseminated cytomegalovirus infection in an immunocompetent woman.

The case of an immunocompetent woman who died of disseminated cytomegalovirus infection with encephalitis and skin ulcerations is reported. The duration of the disease, from onset to death, was five months. Cytomegalovirus was found in the blood, urine, skin, muscle, liver and periventricular brain tissue, but not in frontal cortex tissue. This case underlines the fact that cytomegalovirus may exceptionally cause life-threatening illness in immunocompetent adults.

Adult↗