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From a panel of nine inbred mice strains intranasally infected with Streptococcus pneumoniae type 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial clearance. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca but not BALB/c mice. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 h postinfection. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice, and there was a greater cellular infiltration into the lung tissue of BALB/c mice at the earlier time points. Our data suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils.

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The prevalence of asthma in children has doubled over the past 25 years.1 Two common polymorphisms exist in the adrenoceptor at amino acids 16 (glycine for arginine) and 27 (glutamic acid for glutamine). Both are functionally relevant in cultured cells, with the glycine 16 form of the receptor showing enhanced downregulation and the glutamic acid 27 form showing attenuated downregulation after exposure to agonists.2 The glutamine 27 polymorphism is associated with raised IgE concentrations in families with a history of asthma, and with increased reactivity of the airways in people with asthma.3 4 We measured the prevalence of these polymorphisms in a random population of children to identify their importance in the expression of reported asthma. Subjects, methods, and resultsWe approached children between the ages of 5 and 15 years (mean 10.5 years) and an accompanying parent who were attending the accident and emergency department of the Royal Aberdeen Children's Hospital. Approval from an ethics committee and written consent were obtained from the parents and participating children, and 425 (97%) of 438 agreed to participate. After completing a brief questionnaire each child provided a mouth wash sample (10 ml of boiled distilled water).1 From the resulting suspension of buccal epithelial cells DNA was extracted, and the 2 adrenoceptor polymorphisms were identified using the polymerase chain reaction and an allele specific oligonucleotide assay.3 Frequency tables and Pearson's 2 test were used for bivariate comparisons and logistic regression employed in the multivariate analysis.Complete information including phenotype information on both parents and genotype information in children was available for 410 children with genotyping data in 419. The childhood prevalence of reported asthma (104 out of 425, 24%) was similar to that observed in a recent postal questionnaire study from the same population. 5Thirty nine were arginine 16 homozygotes, 179 were glycine 16 homozygotes, and 201 were heterozygotes. Ninety three were glutamic acid 27 homozygotes, 107 were glutamine 27 homozygotes, and 219 were heterozygotes for the two. The two polymorphisms were in partial linkage disequilibrium. The allelic prevalences of the 2 polymorphisms in this child population were virtually identical with those found in a random sample of adults in Nottingham (unpublished data). Both polymorphisms were in Hardy-Weinburg equilibrium.Genotype at position 16 was not associated with reported asthma. Both homozygosity and heterozygosity for the glutamine 27 polymorphism were associated with reported asthma (table), with a significant association between the presence of this allele and reported asthma ( 2 = 4.38, df = 1, P = 0.04). On logistic regression analysis and taking other known factors into account (sex, maternal asthma, reported hay fever, and eczema) the glutamine 27 allele conferred an independent increased risk of reported asthma (odds ratio 2.18, confidence interval 1.13 to 4.23, P = 0.02). Conversely, homozygosity for the gl...

Development of novel congenic mouse strains has allowed us to better define the location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3. Congenic strains were identified by use of published and newly developed microsatellite markers, their genomes fingerprinted by a rapid, fluorescence-based approach, and their susceptibility to type 1 diabetes evaluated. The maximum interval containing Idd3 is now approximately 4 cM.