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S Langlois

Publications and source records attributed to S Langlois.

At least 73 records · Page 4Linked to original sources
PubMed1993

Increased parental ages and uniparental disomy 15: a paternal age effect?

Parental ages associated with both maternal and paternal uniparental disomy (UPD) of chromosome 15 are highly elevated in comparison to Zurich population-based controls, with mean maternal and paternal ages of 35.6 and 38.1, respectively for UPD patients (diagnosed in Zurich) and 28.0 and 31.0, in controls. The parental ages are also significantly higher than observed for trisomies of other chromosomes diagnosed in Zurich. The higher age of UPD cases may be due to the fact that two errors, both a gain and a loss of a chromosome 15, are necessary. We suggest that gamete complementation, zygote formation from two gametes one of which is nullisomic and the other disomic for the same chromosome, may be a major mechanism of UPD formation, as well as secondary loss of a chromosome in a trisomic conception, and that there is an association between increased paternal age and nondisjunction.

Adult↗
PubMed1993

Non-invasive prenatal fetal testing by analysis of maternal blood.

As the number of women undergoing invasive prenatal diagnosis for cytogenetic, molecular, or biochemical testing is increasing, the development of new non-invasive methods of analyzing fetal cells is imperative. We have analyzed blood from 27 pregnant women (gestational age of 10-11 weeks) by the polymerase chain reaction (PCR) with oligonucleotide primers specific for Y sequences. The sensitivity of our assay, which did not include a step for fetal cell selection prior to PCR analysis, was 45% and the specificity was 89%. A review of the published studies of non-invasive prenatal diagnosis is provided. We conclude from our results and those of others that it is feasible to amplify fetal-specific sequences from maternal blood. However, techniques such as fluorescence-activated or magnetic-activated cell sorting of the maternal blood, as used in other studies, are necessary to enrich for fetal cells prior to analysis. With further improvements of these techniques, it is likely that fetal cell typing from maternal blood will be a feasible method of non-invasive prenatal diagnosis.

Chorionic Villi Sampling↗
PubMed1993

Nondisjunction of chromosome 15: origin and recombination.

Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N = 27) and Angelman syndrome patients (N = 5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination are utilized. Standard methods of centromere mapping are employed to determine the level of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, most paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome.

Aneuploidy↗
PubMed1993

Uniparental disomy for chromosome 16 in humans.

The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally diagnosed. Pregnancy outcome, levels of trisomic cells in term placentas, and fetal uniparental disomy were studied. Intrauterine growth retardation (IUGR), low birthweight, or fetal death was observed in six of these pregnancies and correlated with high levels of trisomic cells in the term placentas. Four of the five cases of IUGR or fetal death showed fetal uniparental disomy for chromosome 16. One of the infants with maternal uniparental disomy 16 had a significant malformation (imperforate anus). All infants with normal intrauterine growth showed term placentas with low levels of trisomic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Genetic diagnosis based on molecular analysis.

This article presents the significant advances made in the area of applied molecular genetics in recent years. DNA analysis is now possible for a large number of single gene disorders. The type of testing available for those disorders most commonly dealt with by pediatricians is briefly outlined. Rapid advancement is expected to continue as new techniques are developed and mutations detected. This in turn will lead to extending DNA applications from the family with an affected child to using DNA for population screening of certain disorders.

Genetic Diseases, Inborn↗
PubMed1991

DNA typing in hereditary disease.

An increasing number of hereditary diseases are becoming amenable to diagnosis by analysis of DNA as the responsible genes are located and identified. Gel electrophoresis of DNA fragments plays a central role in the diagnosis of hereditary disease. Electrophoretic separation of differently sized fragments enables the characterization or typing of normal variants which are known to be genetically linked to disease genes. For some diseases it is possible to directly detect mutations by DNA electrophoresis. Deletion mutants may be detected by a restriction fragment of altered size or by a failure to amplify a coding region with the polymerase chain reaction. Carriers of small deletions, involving a few base pairs, may be identified by DNA amplification which produces heteroduplexes that show characteristic, anomalous electrophoretic migration. Mutations that alter restriction sites also alter the sizes of restriction fragments. Common disease mutations that alter a single base pair may be detected using a pair of reactions with normal and mutant oligonucleotides under conditions where a perfect match is necessary for hybridization, amplification or ligation. Alternatively a mismatched oligonucleotide primer may be designed to generate a restriction site with either the normal or mutant allele, following DNA amplification. Finally a number of techniques are available that are useful as screening tools for novel mutations.

Base Sequence↗
PubMed1990

Familial 5q11.2----q13.3 segmental duplication cosegregating with multiple anomalies, including schizophrenia.

We report on 2 relatives with a segmental duplication of 5q11.2----13.3. The phenotype is surprisingly limited for the degree of chromosome imbalance, the propositus presenting with schizophrenia. Using RFLP markers, we have shown that the gene for HEXB lies within the duplicated region. We suggest this region as a candidate region for the location of a single major gene which predisposes to schizophrenia and which may be assessed by linkage analysis.

Abnormalities, Multiple↗
PubMed1990

Infrared thermographic imaging, magnetic resonance imaging, CT scan and myelography in low back pain.

Sixty-five cases of chronic low back pain were studied. Infrared thermography (IRT) was abnormal in 92%, magnetic resonance imaging (MRI) in 89%, computerized tomography (CT) in 87% and myelography in 80%. IRT correlated with MRI in 94% of cases, and with CT in 87% of cases. Of 22 MRI positive disc and root cases, 21 (95%) had significant leg abnormalities on IRT. All 19 cases with radicular involvement on CT and all 18 with radicular involvement on myelography demonstrated significant leg changes on IRT.

Adult↗
PubMed1989

Electrochemical engineering approach to the irrigation of tooth canals under the influence of a vibrating file.

Doubt exists concerning the irrigation of secondary tooth canals when the vibration of a file introduced into the main root canal is superimposed on flow-through irrigation of the main canal. Depending on the type of commercial equipment used, the vibrations of the file are sonic or ultrasonic. We use the methodology of an electrochemical engineering approach in a study of the intensity of the irrigation of the secondary canals under the influence of sonic and ultrasonic vibrations of a file located at various heights in the main canal. The tooth canals are simulated by small electrochemical cells containing electrodes located at the end of cavities simulating the secondary canals. An electrochemical method is used to measure the mass transfer coefficients at these electrodes, a classical method in electrochemical engineering laboratories. The values of the mass transfer coefficients are representative of the importance of the irrigation of the electrodes. Thus they give a quantitative idea of the vibrations on the irrigation of secondary tooth canals. The work demonstrates the usefulness of the electrochemical engineering approach in contributing to the solution of a biomedical problem.

Electrochemistry↗
PubMed1989

A major insertion accounts for a significant proportion of mutations underlying human lipoprotein lipase deficiency.

Lipoprotein lipase (LPL; triacylglyceroprotein acylhydrolase, EC 3.1.1.34) is an important enzyme involved in triacylglycerol metabolism. Primary LPL deficiency is a genetic disorder that is usually manifested by a severe elevation in triacylglycerol levels. We have used a recently isolated LPL cDNA clone to study 15 probands from 11 families with this inherited disorder. Surprisingly, 7 of the probands from 4 families, of different ancestries, had a similar insertion in their LPL gene. In contrast to other human genetic disorders, where insertions are rare causes of mutation, this insertion accounts for a significant proportion of the alleles causing LPL deficiency. Detailed restriction mapping of the insertion revealed that it was unlikely to be a duplication of neighboring DNA and that it was not similar to the consensus sequence of human L1 repetitive elements. This suggests that there must be other mechanisms of insertional mutagenesis in human genetic disease besides transposition of mobile L1 repetitive elements.

Adult↗
PubMed1988

Interstitial 7q deletion [46,XX,del(7)(pter----q21.1::q22----qter)] and the location of genes for beta-glucuronidase and cystic fibrosis.

We report on a patient with a de novo chromosome abnormality del(7)(q21.1q22). The cells of this patient were used to determine the assignment of the gene for the enzyme beta-glucuronidase and the DNA probes around the cystic fibrosis gene--pJ3.11 and metH. Both the beta-glucuronidase gene and the DNA probes pJ3.11 and metH were found in 2 copies in our patient, indicating that neither locus lies in the deleted segment.

Chromosome Deletion↗
PubMed1988

Pharmacokinetics of diltiazem in patients undergoing continuous ambulatory peritoneal dialysis.

The disposition of a single oral dose of diltiazem hydrochloride was studied in six male patients treated by continuous ambulatory peritoneal dialysis. Peak concentrations were obtained 2 to 4 hours postdose. The mean absorption rate constant was 0.94 +/- 0.21 (sd) hr-1, and the mean elimination half-life was 3.09 +/- 1.16 hr. Serum levels of deacetyldiltiazem, a metabolite of diltiazem, were always below 10 ng/mL. The amounts of diltiazem and deacetyldiltiazem eliminated in dialysate over 24 hours represent less than 0.1% of the administered dose. The pharmacokinetic parameters of diltiazem determined in these patients did not differ from those determined in healthy volunteers and in patients suffering from end-stage renal disease.

Adult↗
PubMed1988

Characterization of six partial deletions in the low-density-lipoprotein (LDL) receptor gene causing familial hypercholesterolemia (FH).

Two hundred thirty-four unrelated heterozygotes for familial hypercholesterolemia (FH) were screened to detect major rearrangements in the low-density-lipoprotein (LDL) receptor gene. Total genomic DNA was analyzed by Southern blot hybridization to probes encompassing exons 1-18 of the LDL receptor gene. Six different mutations were detected and characterized by the use of exon-specific probes and detailed restriction mapping. Each mutation is unique and suggests that molecular heterogeneity underlies the molecular pathology of FH. There appear to be preferential sites within the LDL receptor gene for major rearrangements resulting in deletions.

Chromosome Deletion↗
PubMed1988

A polymorphic DNA marker that represents a conserved expressed sequence in the region of the Huntington disease gene.

A polymorphic marker (D4S62) that is genetically closely linked to D4S10 and is in the region of the gene for Huntington disease is described. A four-allele polymorphism is detected when HincII-digested DNA is hybridized with D4S62. D4S62 maps, by Southern blot analysis using somatic-cell hybrids, to 4p16.1 closer to the centromere than does D4S10. The use of the polymorphisms detected by D4S62 increases the informativeness of markers close to the gene for Huntington disease and will be useful for preclinical diagnosis. D4S62 detects transcripts of approximately 6,000 nucleotides in rat, mouse, and monkey liver and brain. This represents the first demonstration of conserved expressed sequences close to the gene for Huntington disease.

Alleles↗
PubMed1987

First-trimester prenatal diagnosis for Huntington's disease with DNA probes.

Polymorphic DNA probes linked to the locus for Huntington disease (HD) were used for prenatal diagnosis of a 10-week fetus at 25% risk for the disease. The fetus proved to have a 48% risk of having inherited the HD mutation which was similar to that for the at-risk parent (50%). On this basis the parents elected to terminate the pregnancy. When appropriate family members are available and DNA studies are informative, prenatal diagnosis of HD with polymorphic DNA probes can determine the at-risk status of the fetus with 96% accuracy.

Adult↗
PubMed1987

Assay of diltiazem and deacetyldiltiazem by capillary gas chromatography.

A highly sensitive gas chromatographic method for the analysis of diltiazem and deacetyldiltiazem in plasma or serum is reported. After silylation with bis (trimethylsilyl) trifluoroacetamide, separation was obtained on a cross-linked fused-silica column and detection was by electron-capture. The minimum measurable concentrations were 3 and 1 ng/ml for diltiazem and deacetyldiltiazem, respectively. Intra- and inter-day coefficients of variation were less or equal to 6.0 and 8.0%, respectively, for both compounds. The method was used to study the kinetics of a single oral dose of 60 mg of diltiazem hydrochloride in a patient with renal failure.

Biotransformation↗