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L Osborne

Publications and source records attributed to L Osborne.

11 recordsLinked to original sources
PubMed1992

Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene.

The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15,000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the delta F508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a "severe" mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.

Base Sequence↗
PubMed1992

Simple non-radioactive detection of the CFTR mutation N1303K by artificial creation of a restriction site.

N1303K is one of the most frequent non-delta F508 mutations causing cystic fibrosis in Central Europe. Since no restriction site is altered by this mutation and no other frequent mutations are known so far in exon 21, the detection requires a separate and laborious test. A mismatched primer was used to create an artificial Hin dIII site in amplified wildtype DNA, which is destroyed by the mutation. This allows for rapid and convenient detection by restriction enzyme digestion.

Base Sequence↗
PubMed1991

A mutation in the second nucleotide binding fold of the cystic fibrosis gene.

The discovery last year of the deletion of a phenylalanine residue at amino acid position 508 of the cystic fibrosis (CF) gene has meant that approximately 70% of mutant chromosomes associated with CF can be accounted for. We report the finding of a substitution at nucleotide position 4041 of the CF gene, resulting in a change from asparagine to lysine at amino acid position 1303. We believe that this is a disease-causing mutation, as it involves a nonconservative amino acid change and has only been found on CF chromosomes with a consistent haplotype background. The mutation was detected using direct sequencing of PCR-amplified genomic DNA and was confirmed by dot hybridization to both normal and mutant allele-specific oligonucleotides. The mutation was detected on three chromosomes from four individuals but not on any normal chromosome. Its presence in the heterozygous state is not correlated with the clinical status of the individual patients.

Adult↗
PubMed1990

Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis.

The concordance of pancreatic and pulmonary status among siblings with cystic fibrosis, the cystic fibrosis genotype, and non-genetic factors were analysed in adult patients with cystic fibrosis. Genetic factors were more important than non-genetic factors in affecting the severity of pancreatic and lung disease. The genetic factors were independent of each other and did not invariably cosegregate with specific mutations at the cystic fibrosis locus.

Adult↗
PubMed1990

Linked marker haplotypes and the delta F508 mutation in adults with mild pulmonary disease and cystic fibrosis.

The frequencies of the delta F508 mutation and haplotypes at the loci linked to the cystic fibrosis (CF) gene have been compared in adult CF patients with very mild and with severe lung disease. In patients who are compound heterozygotes for the delta F508 mutation, or who lack the mutation on both chromosomes, the as yet undefined mutations may influence the severity of lung involvement. In patients homozygous for the delta F508 mutation, non-genetic factors cannot fully account for variation in the severity of lung disease. Genes outside the CF locus may influence clinical expression of the disease.

Adolescent↗
PubMed1989

Effects of ethanol on human fractionated response times.

The effects of ethanol (EtOH) on response components varying along a central vs. peripheral dimension were studied in five subjects. Reaction times (RTs) were fractionated by electromyographical recordings into premotor (central) and motor (peripheral, contractile) components. Highly practiced subjects performed a simple and discrimination RT task and related movement without significant impairment at the moderate blood ethanol concentration (BEC) (0.10%). At the higher BEC (0.17%), all components involving central processing (response time, RT and premotor time) were impaired in both simple and discrimination RT. More peripheral components (contractile time and movement time) were little affected. Contractile time was slowed slightly but significantly, but only in the combination of EtOH and the discrimination task which suggests that the stimulus discrimination stage of information processing can influence the activation of motor units involved in carrying out the movement.

Adult↗