139 research outputs found
Lack of evidence of a significant association between HLA-DR, DQ and DP genotypes and atopy in families with HDM allergy
No full textBackground: HLA class II genetic polymorphism has been variably implicated in susceptibility to specific immune responsiveness to house dust mite (HDM) allergens, and may also influence the development of atopy.Objective: In order to assess accurately the influence of HLA alleles in the atopic immune response, we typed 22 families selected from 131 previously obtained randomly selected families (i.e. without regard to atopy or asthma), chosen on the basis of two or more members having skin prick reactivity to HDM.Methods: Each individual was fully typed for HLA-DRB1, DQA1, DQB1 and DPB1 class II alleles using a combination of sequence-specific oligonucleotide probes (SSOP) and sequence-specific primer (SSP) polymerase chain reaction (PCR) typing and direct sequencing.Result: Using appropriate statistical tests, no significant allelic associations were found between any DRBl, DQB1 or DPBl alleles and atopy or skin prick reactivity to Dermataphagoides pteronyssinus (Der p) or D. farinae (Der f). However, positive associations were found between DQA 1*0301 and skin prick reactivity to Der f (P= 0.009) and atopy (P= 0.027). Sib-pair analysis revealed no significant sharing of alleles between affected sib pairs for any of the phenotypes studied.Conclusion: These results fail to confirm a previously reported association between the DRB1*04 and 07 haplotypes and atopy, and suggest that HLA class II restriction does not play a major role in the development of the IgE response to domestic house dust mite allergens in the British population.<br/
[Genetic factors involved in asthma and atopy. Studies in British families]
No full textBoth asthma and atopy run families indicating a strong genetic component. To investigate possible candidate gene regions, we have recruited 131 families without reference to atopy and asthma (random sample) and 60 extended families with two or more members affected by asthma (multiplex sample). Using both candidate and genome screen approaches, we have been able to provide evidence supporting the presence of candidate genes on chromosome 11q (E237G) and 12q but we have been unable to confirm reports of linkage and association for asthma on 5q. Our experience to date suggests that larger numbers of families are needed to increase the confidence of gene localisation and there is a need to improve the phenotypic description of asthma. Finally, it is essential that claims for linkage or association are confirmed in different populations using the same markers
Functional heterogeneity of pulmonary surfactant protein-D in cystic fibrosis
No full textPulmonary surfactant protein-D (SP-D) is a soluble collagenous C-type lectin with important anti-microbial and anti-inflammatory properties. Although it is subject to functionally relevant modification by common polymorphisms and unregulated inflammation, the functional status of SP-D in cystic fibrosis (CF) remains unclear. Given the importance of infection and inflammation in CF lung pathology we have undertaken the first systematic analysis of SP-D lectin activity in this population. By ELISA, we found that airway lavage fluid SP-D expression was greater in CF compared to control patients but was reduced in CF patients with infection and correlated negatively with markers of neutrophilic inflammation. In a functional assay, the percentage of SP-D capable of binding zymosan rarely exceeded 60% in CF or control patients and similarly restricted binding activity was observed towards maltose–agarose. SP-D lectin activity also correlated negatively with infection and neutrophilic inflammation but there was little evidence of major proteolytic degradation amongst the non-bound material. SP-D which failed to bind zymosan exhibited features of lower oligomeric form compared to bound material when tested by native gel electrophoresis. Furthermore, when separated by gel chromatography, high and low oligomeric populations of SP-D were observed in CF lavage fluid but only high oligomeric forms exhibited substantial lectin activity towards yeast derived mannan. Our data demonstrate that oligomeric heterogeneity underlies functional diversity amongst SP-D in health and disease and that dynamic regulation of oligomerisation is an important feature of SP-D biology.<br/
Exclusion from proximal 11q of a common gene with megaphenic effect on atopy
No full textWe have typed three markers on proximal 11q in 131 random families with three or more children studied for atopy. A summary map that includes the FCER1B candidate was constructed. Using a 2-locus disease model, we performed combined segregation and linkage analysis of three models, none of which suggested linkage. Nine marker loci on other chromosomes were also negative. In the regions swept by these 12 markers we cannot rule out a rare gene, perhaps of large effect, nor a common gene of small effect. However, a common gene of large effect is excluded. These results and alternative strategies are discussed in the perspective of inconsistent evidence for a major atopy gene
Autonomía política y construcción de la Soberanía en el Imaginario Estadounidense. Un estudio de Teología Política
No full textEl artículo desarrolla, en clave hegeliana, una posible explicación del papel que desempeña la idea protestante de la autonomía subjetiva en la conformación del imaginario político estadounidense, y su paradigma respectivo de la democracia. El punto de arranque es una importante indicación de James Doull, desarrollada luego por David Peddle, sobre lanociónde la venia interna para la aceptación de las instituciones políticas, formulada originalmente en el seno de la tradición calvinista del Pacto. A mi juicio, esta observación es correcta, pero insuficiente para explicar cabalmente la conformación del imaginario de la soberanía del Demos. Siguiendo la línea del propio Doull, cuyo examen proyecta la filosofía hegeliana, lo que se requiere, a mi juicio, es indagar el tipo de experiencia específico de la consciencia americana en el periodo colonial desde la perspectiva de análisis que Hegel desarrolla en la Fenomenología del Espíritu.
Autonomía política y construcción de la Soberanía en el Imaginario Estadounidense. Un estudio de Teología Política
No full textThe article develops, in a Hegelian key, a possible explanation of the role that the Protestant idea of subjective autonomy plays in the shaping of the American political imaginary, and its respective paradigm of democracy. The starting point is an important indication by James Doull, later developed by David Peddle, on the notion of internal consent for the acceptance of political institutions, originally formulated within the Calvinist tradition of the Covenant. In my opinion, this observation is correct but insufficient to fully explain the conformation of the imaginary of the sovereignty of the Demos. Following Doull's own line, whose examination projects Hegelian philosophy, what is required, in my opinion, is to investigate the specific type of experience of American consciousness in the colonial period from the perspective of analysis that Hegel develops in the Phenomenology of the SpiritEl artículo desarrolla, en clave hegeliana, una posible explicación del papel que desempeña la idea protestante de la autonomía subjetiva en la conformación del imaginario político estadounidense, y su paradigma respectivo de la democracia. El punto de arranque es una importante indicación de James Doull, desarrollada luego por David Peddle, sobre lanociónde la venia interna para la aceptación de las instituciones políticas, formulada originalmente en el seno de la tradición calvinista del Pacto. A mi juicio, esta observación es correcta, pero insuficiente para explicar cabalmente la conformación del imaginario de la soberanía del Demos. Siguiendo la línea del propio Doull, cuyo examen proyecta la filosofía hegeliana, lo que se requiere, a mi juicio, es indagar el tipo de experiencia específico de la consciencia americana en el periodo colonial desde la perspectiva de análisis que Hegel desarrolla en la Fenomenología del Espíritu.
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