Search Results - (Author, Cooperation:J. M. Hopkin)

2015-02-25

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Adolescent ; Adult ; Asthma/blood/genetics ; Child ; CpG Islands/genetics ; DNA Methylation/*genetics ; Eosinophils/cytology/metabolism ; Epigenesis, Genetic/*genetics ; Female ; *Genetic Association Studies ; Genome, Human/*genetics ; Humans ; Immunoglobulin E/*blood ; Inflammation Mediators ; Male ; Middle Aged ; Mitochondrial Proteins/genetics ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Transcription Factors/genetics ; Young Adult

1749-6632

Blackwell Publishing Journal Backfiles 1879-2005

Natural Sciences in General

Electronic Resource

1399-3038

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

We have undertaken a double blind placebo controlled study of the effect of nasal beclomethasone on the tendency to wheeze in 20 unselected hay fever sufferers, half with a history of previous seasonal wheezing. We found no difference between either bronchial hyperresponsiveness, as measured by methacholine challenge, home-monitored PEFR, nor recorded wheeze nor cough between treated and placebo groups although the numbers were small. All were allowed the antihistamine cetirizine hydrochloride 10 mg daily. Eighteen out of the 19 patients had either bronchial hyper-responsiveness (PD20 methacholine 〈 8 μmol or a 〉 2 doubling dose change in their PD20 during the pollen season). We have shown a significant positive correlation between a hay fever score (HFS) (created by taking the sum of the home scored; nasal discharge, nasal blockage, eye irritation, sneeze and antihistamine use) and peak seasonal specific IgE to mixed grass pollen (Spearman correlation coefficient 0.5 P〈0.02). There was also a positive correlation between the rise in specific IgE from pre to peak season and the HFS, correlation coefficient 0.6 P =0.03).

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Twenty-five atopic children under 11 years of age were studied, using skin and RAST tests, for their specific IgE response to four species of pyroglyphid house dust mites, Dermatophagoides pteronyssinus, D. farinae, D. microceras and Euroglyphus maynei. All of the children were sensitive to D. pteronyssinus, 20 (80%) of these children were also sensitive to D. farinae and D. microceras, and 16 of the latter (64%) were also sensitive to E. maynei. Dust samples from various sites in the homes of the children revealed D. pteronyssinus in all homes studied but no D. farinae or D. microceras. E. maynei, although identified, was not present in significant numbers in any site. A control group of 20 atopic children of similar age who were not sensitive to house dust mite allergens had a similar exposure to the four mite species. These results suggest that factors in addition to mite exposure are important in the development of specific IgE responses to house dust mites.

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Pairwise analysis of siblings from 21 families showed that house dust mite (HDM) sensitive children were exposed to higher concentrations of Der p I allergen in their mattress (P= 0.005) and bedding (P= 0.04), but not bedroom floor (P= 0.33), than their atopic sibling who was not sensitive to HDM antigens. There was no difference in the exposure to HDM numbers/100 mg of dust in the mattress (P= 0.61) or bedroom floors (P= 0.09). In contrast, pairwise analysis of siblings from 15 families showed that HDM sensitive children were not exposed to significantly different concentrations of Der p I in the mattress (P= 0.96), bedding (P= 0.11) or bedroom floor (P= 0.70) nor HDM numbers/100 mg of dust in the mattress (P= 0.12) and bedroom floor (P= 0.98) than their non-atopic siblings. These findings were identical when absolute allergen load was compared in these pairs. Genetic linkage studies in these families suggest the tendency to atopic IgE responses is conferred by a putative atopy locus on chromosome 11q. These results together suggest that differences in allergen levels in beds, among siblings with a comparable genetic tendency to atopy, play a significant role in determining the development of HDM allergy.

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy.Objective The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan.Methods We conducted a case–control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods.Results Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P=0.0002−0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels.Conclusion These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The results of testing for linkage between atopy and the chromosome 11 marker D11S97 is shown for all the 723 subjects genotyped by us up to January 1992. Lod score estimations were confounded by the high population prevalence of atopy, maternal inheritance of atopy at the 11q locus, genetic heterogeneity, and excess of atopy in families not ascertained through a single proband. Affected sib-pair analysis shows evidence for linkage which is not dependent on the definition of atopy or model specification. We suggest that presentation of sib-pair data will be suitable for meta-analysis of the different studies of genetic linkage and atopy.

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract. In order to test for human histocompatibility leucocyte antigens (HLA) class II restriction of IgE responses, 431 subjects from 83 families were genotyped at the HLA-DR and HLA-DP loci and serotyped for IgE responses to six major allergens from common aero-allergen sources. A possible excess of HLA-DR 1 was found in subjects who were responsive to FeldI compared with those who were not (Odds Ratio (OR) = 2, P = 0.002), and a possible excess of HLA-DR4 was found in subjects responsive to Alt a I (OR = 1–9, P = 0.006). Increased sharing of HLA-DR/DP haplotypes was seen in sibling pairs responding to both allergens. Der p I, Der p II, Phi p V and Can f I were not associated with any definite excess of HLA-DR alleles. No significant correlations were seen with HLA-DP genotype and reactivity to any of the allergens. The results suggest class II HLA restriction is insufficient to account for individual differences in reactivity to common allergens.

Electronic Resource

1365-2222

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2958

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Medicine

Electronic Resource

1365-2958

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Medicine

A 6.8 kjlobase fragment of mJtochondrial DNA from Pneumocystis carinii encodes for apocytochrome b, NADH dehydrogenase subunits 1, 2, 3, and 6, cytochrome oxidase subunit II, and the small subunit of ribosomal RNA. Comparative sequence analysis with a series of organisms representative of the fungal and protozoan groups shows that R carinii has, consistently, an average similarity of 60% with the fungi but only 20% with the protozoa. The data indicate homology with the fungi for this opportunistic pathogen.

Electronic Resource

1398-9995

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

We recently described a protective effect of the low molecular weight protein tyrosine phosphatase (LMPTP) BC genotype, associated with the highest total enzymatic activity, against high serum IgE levels both in the English and the Italian populations. Here we test the hypothesis of a role of LMPTP in the negative modulation of IL-4 signal transduction checking for genetic interaction between interleukin-4 receptor alpha chain (IL-4RA) genetic polymorphisms and LMPTP polymorphism in the predisposition to high total IgE levels in the English population. We find a significant interaction between LMPTP polymorphism and the intracellular Gln/Arg polymorphism in position 551 of IL-4RA. Our data support the hypothesis of a direct or indirect biochemical interaction between LMPTP and IL-4RA resulting in different modulation of IL-4 signal transduction among joint genotypes.

Electronic Resource

1398-9995

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Atopy is the state of allergy to common environmental antigens. Genetic and environmental factors promote the disorder. The impressive rise in prevalence, mainly centred on socio-economically developed communites around the world, emphasizes the potent action of environmental factors in moulding this immune disorder which is characterized by inadequately restrained Th-2 immune mechanisms and IgE production. Reversing the epidemiological trend depends on our identifying the major environmental inputs and acting against these. As yet, the nature of these environmental factors remains to be clarified. Candidate factors include changes in diet, chemical air pollution and microbial exposures in developed countries. This article limits its scope to changing microbial exposures as a potential mechanism. (a) It records epidemiological data that have associated atopic status with less natural exposure to pathogens, parasites and commensal micro-organisms, but with more exposure to certain antibiotics and public health immunizations in early life. (b) It records studies in mice that support the concept that certain microbial exposures can inhibit experimental allergy. (c) It considers potential immune mechanisms for such an action, including the possibility that certain natural infections promote immune regulatory processes that can restrain atopy. It is concluded that the hypothesis that changing patterns of microbial exposure may have promoted the rise in atopy is viable, and that exciting possibilities for reversing the rise of atopy may be derived from further studies.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] The responses of cultured lymphocytes from four groups of people to four doses of smoke condensate were examined by the visual scoring of induced SCEs. We used the same methods as in our original report6 and, as before, samples were coded and scored 'blind'. Smoke condensate produced from a ...

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Table 1 Cigarette condensate yields Average dimensions of Weight of condensate Tar cigarette (wet in mg) category of Length Weight Butt length collected from 24 cigarettes cigarette (mm) (mg) (mm) smoked together* High 70 1,008 20 1,020 Middle 70 988 20 530 Low ...

Electronic Resource

1432-1203

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract The gene encoding Clara cell-derived inflammatory molecule CC16 has been cited as a candidate gene for atopic asthma on chromosome 11q13. A genetic association study was performed with variants of the CC16 gene on chromosome 11q13 in relation to asthma in British (n=275) and Japanese (n=300) populations. No significant association was found between asthma and CC16 genotypes, irrespective of atopic status in these two populations. These data suggest that CC16 might not be the major locus for asthma on 11q13.

Electronic Resource