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Biomedical subjects

M W Turner

Publications and source records attributed to M W Turner.

At least 19 recordsLinked to original sources
PubMed1992

Identical point mutation leading to low levels of mannose binding protein and poor C3b mediated opsonisation in Chinese and Caucasian populations.

A common opsonic defect occurring in 7% of the Caucasian population is associated with low serum levels of the lectin mannose binding protein (MBP). This study sought to determine whether the deficiency was also present in a Chinese population using sera obtained from 100 healthy Chinese children (age range 6 weeks-16 years). The distribution profiles of MBP levels and C3b/C3bi fragments binding to mannan coated plates were both bimodal and similar to the corresponding Caucasian profiles. Serum MBP levels were low in 9% of the Chinese children and all of these sera generated low levels of C3b/C3bi fragments. Overall there was a high significant correlation between MBP levels and C3b opsonin generation (r = 0.77; P less than 0.001). By analogy with similar findings in a Caucasian population we believe this correlation to be a reflection of antibody independent complement activation by MBP. In a pilot study of DNA obtained from three adult Chinese with low MBP levels the point mutation causing MBP deficiency in Caucasians was identified in all three cases.

Adolescent↗
PubMed1992

High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene.

We have previously identified, in three British families having an index child with frequent infections, a point mutation (GGC-->GAC) in codon 54 of exon 1 of the gene for the human lectin mannose binding protein (MBP). This was associated with low serum levels of this complement activating protein and would be anticipated to impair opsonization of mannose rich microorganisms. We now report a second point mutation (GGA-->GAA) in Gambians from West Africa, involving codon 57 of exon 1. By substituting carboxylic acids for axial glycines in the translated proteins both mutations would be expected to disrupt the secondary structure of the collagenous triple helix of the 96 kDa MBP subunits. In the Gambians the codon 57 mutation was studied by PCR, sequence analysis and restriction analysis and found to be remarkably common (frequency of the mutant gene 0.29 in adults and 0.23 in newborns) whereas the codon 54 mutation was very rare (frequency 0.003). However, the codon 54 mutation was frequent in both a British Caucasian and a Hong Kong Chinese population (frequency of the mutant gene 0.17 and 0.11 respectively). It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway. Our data indicate that the two mutations have arisen independently since the divergence of African and non African populations and both have attained high frequencies.

Adult↗
PubMed1992

Role of cell wall polysaccharide in the assessment of IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae in childhood.

The interference of antibodies to pneumococcal cell wall polysaccharide (CWPS) in the measurement of antibodies to capsular polysaccharides in children was assessed after vaccination with pneumococcal polysaccharide vaccine. ELISAs were developed to measure IgG subclasses specific for pneumococcal types 3, 6, 19, and 23 and CWPS. Analysis of antibody levels to all four capsular polysaccharides was affected by the presence of antibodies to CWPS, and their removal altered both anti-capsular polysaccharide antibody levels and the interpretation of responses to the vaccine. Thus, it is likely that CWPS contaminating pure capsular polysaccharide reagents used in most standard immunoassays is responsible for falsely elevated measurements of antibodies to capsular polysaccharide and the incorrect assessment of anti-pneumococcal antibody status in childhood.

Adolescent↗
PubMed1991

Molecular basis of opsonic defect in immunodeficient children.

Low serum mannose-binding protein (MBP) concentrations are associated with a common opsonic defect. Sequence analysis of the MBP gene in three children with recurrent infections, the opsonic defect, and low serum MBP concentrations showed a point mutation at base 230 of exon 1 causing a change of codon 54 from GGC to GAC. The replacement of glycine with an aspartic acid residue disrupts the fifth Gly-Xaa-Yaa repeat in the collagen-like domain of each 32 kD MBP peptide chain and probably prevents the formation of the normal triple helix. Study of sixteen members of the three families showed autosomal dominant co-inheritance of the mutation and low serum MBP concentrations.

Alleles↗
PubMed1991

Childhood asthma: clinical and immunological changes over a decade.

A group of 26 Australian asthmatic children with laboratory-proven bronchial hyper-reactivity to the allergens of rye grass pollen and/or the house dust mite has been studied over a 9-year period. Clinical symptoms and drug scores were used to evaluate the severity of the patients' asthma and, wherever possible, blood samples were obtained before, during and after the rye grass pollen seasons. The cumulative symptom and drug scores for the 20 patients with bronchial hyper-reactivity to rye grass pollen extract tended to increase during and fall after each pollen season but the peaks were of decreasing amplitude over the 9 years. Since a proportion of these patients underwent hyposensitization to rye grass during year 1, longitudinal comparisons were made between year 2 and year 9. Comparing the individuals at the same three seasonal time-points revealed significantly lower drug scores in year 9 compared with year 2, and in parallel with this, significantly lower total IgE, IgE anti-rye and IgG anti-rye antibodies at all three assessment points. In the 14 patients with bronchial hyper-reactivity to house dust mite the severity of the asthma and the median levels of IgE and IgG mite specific antibodies all decreased over the study period. Despite the progressive improvement in asthma and diminishing immune responses to both rye grass and house mite in the patients, no immunological feature could be identified that correlated significantly with clinical outcome.

Adolescent↗
PubMed1990

Branhamella catarrhalis: antigenic determinants and the development of the IgG subclass response in childhood.

A recently developed whole cell ELISA was used to investigate the development of IgG subclass antibodies to Branhamella catarrhalis in childhood. In addition, SDS-PAGE and immunoblotting were used to study the interaction between the outer membrane proteins (OMPs) of B. catarrhalis and IgG subclass antibodies. Specific IgG3 antibodies were undetectable or present only in low amounts in children less than 4 years old but were an important constituent of the response of older children. OMPs prepared from different isolates had similar molecular masses and bound IgG with identical immunoblotting patterns. Binding appeared subclass-specific, with IgG3 binding to the broadest range of OMPs. These findings should provide a better understanding of the pathogenic role of this organism and suggest possible strategies for the development of a vaccine.

Agammaglobulinemia↗
PubMed1978

Defective yeast opsonization and C2 deficiency in atopic patients.

Twenty-seven per cent of atopic patients initially presenting with infantile eczema or hay fever were defective for yeast opsonization and 18% had low levels of C2; these deficiencies were mutually exclusive, suggesting that they are primary. Both defects were associated with each of four different atopic syndromes, some of which were related to certain HLA haplotypes.

Adolescent↗
PubMed1977

Prevention of eczema.

In a prospective study of the development of reaginic allergy, infants of allergic parents were either subjected to an allergen-avoidance regimen from birth for six months or managed conventionally. The group on the allergen-avoidance regimen had less eczema at six months and one year than did the control group at six months. They also had a lower mean serum-total-IgE level at six weeks.

Allergens↗
PubMed1977

IGE in human urine and milk.

IgE was found in urine from healthy adult volunteers at very low levels (approximately 0.003-0.010 IU/ml), corresponding to a 24-h excrection rate of 3-16 IU. IgE was not detected in 36 out of 47 samples of milk and colostrum. In samples from six women the protein was present at low concentration 1-2 days postpartum but was not detected in later samples (usually day 5 or 6). Mammary secretions from four allergic donors were studied, and IgE was detected at low concentrations in samples from the two most severely affected individuals. The levels of IgE observed in both urine and milk suggest that there is no significant synthesis of the protein in either the urinary tract or in mammary tissue.

Adult↗
PubMed1977

HLA in eczema and hay fever.

The presumed HLA haplotype A1:B8 was more frequent and the combination of A3 and B7 was less frequent in allergic subjects presenting with eczema, than in those presenting with hayfever. A1:B8 was most frequent (36%) in eczema complicated by asthma and/or hay fever, and least frequent (5%) in hay fever alone, considerably above and below the frequency in the general population (17%).

Adolescent↗
PubMed1976

HLA antigens and atopic features in steroid-responsive nephrotic syndrome of childhood.

Atopic systems were more common in children with steroid-responsive nephrotic syndrome (S.R.N.S.) than in matched controls, and HLA-B12 was more common in children with S.R.N.S. than in adult controls. Atopic symptoms (particularly hayfever), positive prick tests with grass pollen antigens, and a higher mean serum concentration of IgE antibody to timothy grass pollen were more common in nephrotic children with HLA-B12 than in those without HLA-B12. There was also an increased frequency of the haplotype HLA-A1 and HLA-B8, mainly among the non-atopic patients.

Adolescent↗
PubMed1976

Predisposing factors and the development of reaginic allergy in infancy.

In a prospective study of fifty-eight newborn infants of parents with reaginic allergy, twenty-seven developed eczema and twenty-eight positive prick tests to one or more of six antigens during the first year of life. These reaginic manifestations were related to presymptomatic transient IgA deficiency. The development of positive skin tests was also related to HLA A1 B8, and to season of birth. The order of frequency of positivity was Dermatophagoides, grass pollens, cat fur, feathers and cow's milk. The skin tests were often positive in infants in whom serum IgE was not detected. The eczema disappeared and the skin tests became negative in some infants at the end of the first year. This work suggests that sensitization in the new-born period is important in the subsequent development of disease.

Antibodies↗