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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Atopy, with or without associated asthma, provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class II gene products are involved in the control of immune responses.Objectives We investigated whether susceptibility or resistance to the disease was associated with HLA class II genes.Methods Blood samples were obtained from two groups of unrelated European-born white adults: 56 atopic patients (52 of them with asthma) and 39 healthy controls with no personal or familial history of asthma or atopy. Genomic DNA was extracted from peripheral blood lymphocytes. The exons of DQA1, DQB1, DRB and DPBl genes were selectively amplified by the polymerase chain reaction (PCR) method. Geno-typing was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which can recognize allelic variations in the polymorphic exon.Results We found no significant difTerences in the frequency of DPBl alleles between patients and controls. HLA class II DR4 and DR7 alleles were present in 39.2% of the patients and in 2.5% of the healthy subjects (Pc*2± 3.9 10−3). Conversely, DQA1*0103 and DQB1*0502 alleles were more frequent in the control subjects. These results confirm a previous study of an extended pedigree, which showed that DR4 and DR7 alleles were absent in all healthy members of the family and were frequently observed in atopic and/or in asthmatic subjects.Conclusion We observed that HLA-DR 4 and DR7 alleles are significantly implicated in their susceptibility to the disease and suggest that this susceptibility is more related to atopy than to specific responses to allergens. According to previous studies, we could also submit that in atopic patients with asthma, DR4 alleles at the least, could be more closely associated with atopy than with asthma per se. Conversely, we suggest that some allelic DQA1 and DQB1 sequences might confer protection against the disease.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Nasal polyps are characterized by a proliferation of the epithelial layer of the mucosa. cellular infiltrates and other pathological changes; however the mechanisms involved in polyp pathogenesis remain largely unclear.Objectives We have taken two different approaches to study the cellular events involved in nasal polyposis.Methods First, through use of immunohistochemical methods, we have studied the expression of HLA class II antigens in epithelial cells of nasal polyps and the distribution of lymphocytes in the epithelium and in the subepithelial layer in patients with clinical conditions, such as asthma, atopy, aspirin intolerance or cystic fibrosis, and in subjects with an absence of concomitant diseases. Second, in order to investigate whether HLA class II expression is controlled at the pre- or post-transcriptional level, we studied the effect of interferon gamma (INFγ) on epithelial cells in primary culture, which were derived from HLA class II negative and HLA class II positive nasal polyps. Total RNA was extracted from the cells and reverse-transcribed, and the c-DNA corresponding to DR, DP, DQ loci was amplified by PCRResults Expression of HLA class II antigens by the epithelia of nasal polyps was more common in the presence rather than in the absence of concomitant asthma, atopy or cystic fibrosis (59% versus 409%). HLA-DR was the only HLA class II antigen expressed in the seven polyps taken from cystic fibrosis patients. The number of CD8+ cells was significantly higher in polyps associated with known clinical conditions and HLA class II antigen expression than it was in ‘isolated’ polyps and in HLA class II negative polyps. RNA transcripts for at least one or all three HLA-DR, DP and DQ antigens were detected in 10 cultures of the 11 HLA class II positive polyps. Conversely, 8 of 10 cultures derived from HLA class II negative polyps did not express HLA class II transcripts in the absence of INFγ. Adding INFγ (100U/ml) to the latter cell cultures caused expression of transcripts of one or more HLA class II genes.Conclusions We have shown that HLA class II antigens were more frequently detected in polyps of patients with an identified clinical syndrome than in those of asymptomatic subjects. Our results also suggest that IFN γ regulates expression of HLA class II antigens in airway epithelial cells of the nasal polyps at the transcriptional level, and that cultured cells from nasal polyps represent a suitable modei to investigate immune mechanisms involved in diseases such as atopy, asthma and cystic fibrosis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0167-4889
    Keywords: Cell separation ; Density gradient centrifugation ; Differentiation control ; Insulin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0167-4889
    Keywords: (Rat preadipocyte) ; Differentiation ; Glucagon ; Hormone sensitivity ; Insulin ; Isoproterenol ; Lipogenic enzyme ; Lipoprotein lipase
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 54 (1999), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Allergic asthma is a multifactorial and probably multigenic inflammatory disease of the upper airways, and has been associated with the HLA class II alleles DR4 and DR7. Here we investigated possible associations with other polymorphic susceptibility/resistance genes located within the major histocompatibility complex, i.e., the genes coding the major 70-kDa heat-shock proteins (HSP; Hsp70) hsp70–1, hsp70–2, and hsp70-HOM, whose products are overexpressed in the bronchi of asthmatic patients. Methods: Genomic DNA was extracted from peripheral blood lymphocytes or buccal epithelial cells of 48 patients with allergic asthma and 31 selected nonatopic control subjects, in whom we previously reported a strong association of atopy with DR4/DR7 alleles.Results: No evidence was found for an independent role of hsp70 gene polymorphism in susceptibility to allergic asthma. However, hsp70 alleles might be involved in extended haplotypes of HLA markers. Conclusions: Our data suggest that Hsp70 overexpression in asthma results from complex interactions between environmental exposures and genetic background rather than from specific genetic variations in hsp70 genes.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-9071
    Keywords: Key words. Heat shock element; promoter; allelles; binding-activity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. A bi-allelic polymorphism found in the regulatory region of the human heat shock (HS) protein (HSP) hsp70-1 gene, which comprises an A→C transversion, 3 bp upstream of the HS element (HSE), has been associated with extended HLA haplotypes. In view of the chaperoning and protective functions of Hsp70, we investigated whether this hsp70-1 bi-allelic polymorphism could modulate the stress response, which may relate to enhanced resistance or susceptibility to certain diseases. We compared the basal and HS-induced HS factor (HSF)-binding activity of the two polymorphic HSEs, hsp70-1 mRNA accumulation and HSP expression in two human Epstein–Barr virus (EBV)-transformed B cell lines typed for hsp70-1 promoter alleles. Our results suggest that hsp70-1 promoter polymorphism does not influence HSF-binding activity, hsp70 mRNA accumulation or synthesis in human EBV-transformed B cell lines.
    Type of Medium: Electronic Resource
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