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Biomedical subjects

R Williamson

Publications and source records attributed to R Williamson.

At least 415 records · Page 23Linked to original sources
PubMed1983

Absence of maternal contamination of chorionic villi used for fetal-gene analysis.

Chorionic villi can be obtained by direct transcervical aspiration at 9 to 10 weeks' gestation and used for analysis of fetal DNA. However, for the method to be reliable, there must be no detectable contamination by maternal DNA. To investigate the question of contamination, we compared the DNA of chorionic villi from five fetuses with that obtained from maternal lymphocytes, using the restriction endonuclease Taql and specific DNA probes for a pair of alleles on the X chromosome. The alleles yield fragments of different lengths when digested with Taql (length polymorphism), which can be demonstrated by electrophoresis and hybridization with the radioactive DNA probes. If the pattern obtained with the chorionic DNA is different from that obtained with the maternal DNA, contamination is not present. In two cases the fetal DNA of the chorionic villi was shown to be uncontaminated by maternal tissue. In one of these cases the mother was heterozygous and the fetus was homozygous; in the other the mother was homozygous and the fetus was heterozygous. In three other cases no definitive conclusions could be drawn, because the genotypes of the fetus and mother were identical. We conclude that chorionic villi at 9 to 10 weeks' gestation are a source of fetal DNA that can be used for gene analysis, with no detectable contamination by maternal DNA.

Alleles↗
PubMed1983

Treatment of hypertension following endotracheal intubation. A study comparing the efficacy of labetalol, practolol and placebo.

Labetalol, a new adrenergic receptor antagonist, has both alpha- and beta-blocking properties. Intravenous labetalol (0.25 and 0.5 mg/kg), practolol (0.4 mg/kg) and saline (1 ml), injected prior to anaesthesia, were compared with respect to their effect on the haemodynamic consequences of direct laryngoscopy followed by the passage of an endotracheal tube. When compared with intravenous saline injection, both labetalol and practolol obtunded the tachycardia induced by endotracheal intubation. The higher dose of labetalol was more effective in reducing the hypertensive response than the lower dose of practolol. However, none of the regimens completely abolished the adverse haemodynamic consequences of laryngotracheal manipulations.

Blood Pressure↗
PubMed1983

Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome.

The inheritance of two restriction fragment length polymorphisms (RFLPs) on the short arm of the human X chromosome has been studied relative to Duchenne muscular dystrophy. This provides a partial genetic map of the short arm of the human X chromosome between Xp110 and Xp223. The data were derived from the segregation between a RFLP located at Xp21-Xp223, the DMD locus, and a RFLP located at Xp110-Xp113. The genetic distance from Xp110 to Xp223 was found to be approximately 40 centimorgans (cM). This provides experimental confirmation that 1cM corresponds to approximately 1,000 kilobase pairs of DNA for this region of the human X chromosome. Our data confirm that the DMD mutation lies between Xp223 and Xp110. The availability of flanking probes surrounding the DMD locus will assist in the ordering of further DNA sequences relative to the mutation.

Alleles↗
PubMed1983

The isolation of cDNA clones for human apolipoprotein E and the detection of apoE RNA in hepatic and extra-hepatic tissues.

We have isolated cDNA clones coding for apolipoprotein E (apoE) from a cDNA library prepared from adult human liver mRNA. Mixtures of 128 different oligonucleotides, 17 residues long were synthesised to be complementary to regions of the mRNA corresponding to amino acids 1-6 and 151-156. Five independent apoE clones were selected by direct screening of 5000 recombinants with the two oligonucleotide mixtures. Two overlapping clones contain the 3'-untranslated sequence, the entire coding sequence and an additional 30 bases 5' to the amino terminus of the mature protein. The DNA sequence has been determined spanning the known sites of amino acid substitutions which account for the observed protein polymorphism of apoE. Using the clones as probes in Northern blot analysis of total human liver and kidney RNAs and leucocyte poly(A)+ RNA we have detected a single species of mRNA in liver and kidney of 1.2 kb and two larger species in leucocyte RNA. The level of expression of the mRNA in kidney is approximately 10% of that in liver while the level of apoE RNA sequences in the leucocytes is less than 1% of that in the liver.

Adult↗
PubMed1983

Methods to analyse the human genome.

There is much interest in the use of gene-specific probes for the study of dysfunction in human pathology. For the haemoglobinopathies, globin gene recombinants (either prepared from DNA sequences complementary to messenger RNA, or from genomic DNA) are used to determine whether globin genes are present, whether they are expressed in the nucleus, and whether they are correctly processed to give functional mRNAs. This has not only allowed a fuller understanding of the molecular aetiology of the thalassaemias, but also permitted antenatal diagnosis both by direct analysis of the gene lesion, and by linkage analysis using adjacent genes. Similar approaches are being applied to many other single gene defects. There are, however, other possible ways to study human hereditary disease using recombinants. It is now feasible to use random human chromosome-specific sequences to establish a linkage map for the entire human genome. Such a map may then be used either to determine the chromosomal localisation of any "single gene" phenotype by linkage analysis, or to study the contribution of different genes to a complex phenotype determined by several genes, as in multifactorial disease.

Chromosome Mapping↗
PubMed1983

On the genetic length of the short arm of the human X chromosome.

Published estimates of the length of the human X chromosome are unreliable because they are based on scanty linkage data and complex assumptions about the frequency and distribution of chiasmata in female meiosis. In recent months we have established linkage between restriction fragment length polymorphisms (RFLPs) and several genes on the short arm of the X chromosome. These and previous data can be combined to construct a continuous linkage map spanning the short arm from the Xg gene to the centromere. They suggest that the genetic length of the Xg-Xcen segment may be in the order of 75-90 cM.

Chromosome Mapping↗
PubMed1983

Genetic linkage relationship between the Xg blood group system and two X chromosome DNA polymorphisms in families with Duchenne and Becker muscular dystrophy.

The existence of linkage has been investigated between the Xg blood group system, two DNA restriction fragment length polymorphisms (RFLPs) located on the short arm of the X chromosome, Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). No linkage was found between the Xg locus and the more proximal RFLP (L 1.28); close linkage between Xg and the more distal RFLP (lambda RC8) was also excluded. Both RFLPs show linkage with DMD but are not closely linked with each other. Analyses of 11 families with DMD and ten with BMD, informative for the Xg blood group, reinforce the conclusions of others that there is no measurable linkage between the loci for Xg and for the X-linked forms of muscular dystrophy.

Blood Group Antigens↗
PubMed1983

Sir Busick Harwood: a reappraisal.

Sir Busick Harwood was Professor of Anatomy in the University of Cambridge from 1785 to 1814 and simultaneously Downing Professor of Medicine from 1800 to 1814. Some historical accounts suggest that he was not highly regarded either as a scientist or a teacher, and this note attempts to restore his academic reputation and show how his achievements helped to initiate improvements in medical education at that time.

Anatomy↗
PubMed1983

A model system to demonstrate that beta-lactamase-associated antibiotic trapping could be a potential means of resistance.

Addition of beta-lactamase to cultures of antibiotic-sensitive Escherichia coli protected the bacteria against lysis induced by either a hydrolyzable (cephalothin) or relatively nonhydrolyzable (ceftriaxone) cephalosporin. The later addition of a nonhydrolyzable, non-lysis-inducing beta-lactam antibiotic (oxacillin), which had a higher affinity for the beta-lactamase than ceftriaxone, allowed the reversal of the protection and the onset of lysis. These results suggest that trapping of the antibiotic by the enzyme, without significant hydrolysis, is a reversible process that may play a role in the resistance of some gram-negative bacteria to third-generation cephalosporins.

Cefotaxime↗
PubMed1983

Studies on the mechanism of intrinsic resistance to beta-lactam antibiotics in group D streptococci.

Six penicillin-binding proteins (PBPs) were detected in clinical isolates of each one of three group D streptococci: Streptococcus bovis, S. faecalis and S. faecium. When examined in whole organisms, the PBPs of S. faecium, the most penicillin-resistant species of group D streptococci, generally had lower affinities for the antibiotic than those of S. faecalis (intermediate penicillin resistance), which in turn were of lower affinity than those of S. bovis (penicillin-sensitive). On the other hand, no quantitative correlation could be established between the binding of penicillin to any one PBP or group of PBPs, and the penicillin MIC value for the corresponding micro-organism. Examination of the amounts of antibiotic bound and the rates of binding to PBPs of equal numbers of protoplasts and whole bacteria of S. faecalis and S. faecium, indicated that there was no permeability barrier to benzylpenicillin in the cell walls of these species. The lower antibacterial effectiveness of cephalothin compared with ampicillin in group D streptococci was paralleled by the higher concentrations of cephalothin needed in competition assays to inhibit the lower molecular size PBPs of these bacteria.

Ampicillin↗
PubMed1983

Absence of genetic heterogeneity in Duchenne muscular dystrophy shown by a linkage study using two cloned DNA sequences.

A linkage study using two different restriction fragment length polymorphisms (RFLPs) identified with cloned DNA sequences has failed to provide evidence for genetic heterogeneity in Duchenne muscular dystrophy (DMD) when tested against intelligence quotient (IQ). Analysis of data for age of confinement to a wheelchair against IQ gave no evidence for heterogeneity. These results are of a practical as well as theoretical significance, since the existence of multiple loci causing DMD would make it more difficult to apply linkage data to genotype prediction in this disease.

Child↗
PubMed1983

Linkage analysis of myotonic dystrophy and sequences on chromosome 19 using a cloned complement 3 gene probe.

Variations in DNA sequence generate polymorphisms which can be followed through families. A cloned gene specific probe for human complement 3 (C3) was hybridised to DNA samples digested with restriction endonucleases. The C3 probe detects several restriction fragment length polymorphisms (RFLPs) that occur frequently in the general population. These DNA alleles can be readily used in linkage analyses of loci on chromosome 19, since most families studied are informative. The inheritance of one such polymorphism was followed through myotonic dystrophy families. The segregation data for both the C3 protein polymorphism and the C3 RFLP support the linkage of myotonic dystrophy (DM) and C3.

Chromosome Mapping↗
PubMed1983

Cystic fibrosis is not caused by a defect in the gene coding for human complement C3.

A human genomic clone containing a portion of the structural gene for the third component of complement (C3) was used as a hybridization probe to DNA from two genetically informative families in which cystic fibrosis (CF) occurs. Several restriction fragment length polymorphisms (RFLPs) can be identified using the C3 probe, which appears to detect a high level of sequence variation in the general population. The inheritance of C3 RFLP was found to be independent of the inheritance of the CF phenotype. Assuming that CF is caused by a mutation affecting a single genetic locus, the demonstration that an allele of the C3 gene does not segregate with CF proves that a defect of complement C3 cannot be the cause of the disease.

Complement C3↗