المؤلفون: Rak, S. G.¹ Simone.Rak@tiho-hannover.de, Drögemüller, C.¹, Leeb, T.¹, Quignon, P.², André, C.², Scott, A.³, Breen, M.³, Distl, O.¹

المصدر: Cytogenetic & Genome Research. 2003, Vol. 101 Issue 2, p130-135. 6p. 1 Color Photograph, 2 Charts.

مصطلحات موضوعية: *GENE mapping, *CYTOGENETICS, *GENETIC disorders, *FLUORESCENCE in situ hybridization, *ANIMAL genetics, *ANIMAL genome mapping

مستخلص: The analysis of inherited diseases in the domestic dog (Canis familiaris) provides a resource for the continued use of this species as a model system for human diseases. Many different dog breeds are affected by congenital sensorineural deafness. Since mutations in various genes have already been found causative for sensorineural hearing impairment in humans or mice, 20 of these genes were considered as candidates for deafness in dogs. For each of the candidate genes a canine BAC clone was isolated by screening with heterologous human or murine cDNA probes. The gene-containing BAC clones were physically assigned to the canine genome by FISH and the BAC-derived STS-markers were positioned with the RHDF5000 panel on the canine RH map. The mapping data, which confirm the established conservation of synteny between canine and human chromosomes, provide a resource for further association studies in segregating canine populations and the basis for new insights into this common canine and human disease. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

المؤلفون: Nouri–Aria, K.T., Masuyama, K., Jacobson, M.R., Rak, S., Lowhagen, O., Schotman, E., Hamid, Q., Durham, S.R.

المصدر: International Archives of Allergy & Immunology; Dec1998, Vol. 117 Issue 4, p248-254, 7p

مصطلحات موضوعية: GRANULOCYTE-macrophage colony-stimulating factor, ALLERGIC rhinitis, ALLERGENS, COLONY-stimulating factors (Physiology), EOSINOPHILIA

مستخلص: Background: Allergen–induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2–type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage–colony stimulating factor (GM–CSF) may contribute to late–responses and tissue eosinophilia and is inhibitable by topical corticosteroid. Methods: Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM–CSF. Results: Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5–fold increase in cells expressing mRNA for GM–CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM–CSF mRNA[sup +] cells were co–localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM–CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM–CSF. Conclusions: The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM–CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM–CSF from T lymphocytes or reducing autocrine production of GM–CSF from eosinophils. [ABSTRACT FROM AUTHOR]

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