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The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.   相似文献   
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The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.   相似文献   
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Bronchial hyperreactivity to histamine 4 days following vaccination with the human respiratory pathogenHaemophilus influenzae was tested in twoin vivo and onein vitro models. Conscious vaccinated guinea pigs exposed to aerosolized histamine became asphyxial significantly faster than saline-treated controls. Also the bronchoconstriction in anaesthetized guinea pigs as a result of i.v. histamine was significantly potentiated in theH. influenzae pretreated group. Isoprenaline (30g/kg) partially inhibited the bronchoconstriction. The difference in histamine sensitivity between the two groups however remained. Protection against bronchoconstriction by atropine on the other hand was significantly enhanced in the vaccinated animals. This suggests a hyperreactivity of the parasympathetic, cholinergic pathways as a result ofH. influenzae vaccination.To whom correspondence should be addressed.  相似文献   
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Guinea pigs were inoculated intra-tracheally with bovine parainfluenza type 3 virus (PI-3) to investigate airway responsiveness to histamine and arecolinein vitro. Two days after saline or PI-3 inoculation no difference in the reactivity of the tracheal spirals was observed after cumulative concentration/response curves with both drugs. Similarly, contractions of parenchymal strips, induced by histamine, did not differ between both groups. However, 4 days after PI-3 inoculation the histamine induced contraction of the tracheal spirals was increased by 47% and the arecolinc induced contractions by 32% as compared to the control group. Further, the contractions induced by histamine in parenchymal strips were significantly enhanced (p<0.01) in the PI-3 treated group. In conclusion, PI-3 infection of guinea pig respiratory tract induces hyperreactivity of the central and peripheral airwaysin vitro.  相似文献   
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Kloek  J.  Van Ark  I.  De Clerck  F.  Bloksma  N.  Nijkamp  F. P.  Folkerts  G. 《Inflammation research》2003,52(3):126-131
OBJECTIVE AND DESIGN: Since oxidative stress contributes to the pathogenesis of asthma, this study addressed the question whether supplementing the endogenous antioxidant, glutathione (GSH), would alleviate features of allergic asthma in the mouse. MATERIAL AND METHODS: Ovalbumin-sensitized mice received aerosols of the GSH-donors, glutathione-ethyl ester (GSEt) or N-acetylcysteine, before or during respiratory allergen challenges, or during methacholine challenges given one day after the last allergen challenge. Lung GSH levels were measured shortly after allergen or methacholine challenge. In addition, the effect of GSH supplements on airway hyperresponsiveness and inflammatory cell numbers in the airway lumen was assessed. RESULTS: GSEt decreased allergen-induced airway hyperresponsiveness when given in combination with methacholine. However, when given before or during allergen challenge, both GSH-donors failed to decrease the methacholine-induced airway contractility, change cell numbers in the airway lumen, or increase lung GSH levels. In addition, allergen challenges of sensitized mice did not decrease lung GSH levels. CONCLUSION: In contrast to guinea pigs and humans, allergen challenges in mice does not lead to acute oxidative stress.  相似文献   
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1. Motor responses to des-Arg9-bradykinin and bradykinin were studied in the isolated mouse trachea (precontracted with carbachol, 10 microM) and the urinary bladder of either Swiss, C57B1/6J or bradykinin B2 receptor knockout (Bk2r(-/-)) mice after 1-6 h in vitro. The expression of mRNA for the mouse B1 receptor in tracheal and urinary bladder tissues was also studied by using Northern blot analysis. 2. In isolated tracheae, des-Arg9-bradykinin produced a relaxant response that increased over time: no response was observed after 1 h of incubation, whereas after 6 h the maximum response (1 microM) was 68-84% of the relaxation produced by isoproterenol (1 microM) in the three mouse strains. The relaxant response to bradykinin (1 microM) observed at 1 h (38-51% of isoproterenol) was increased (62-65% of isoproterenol) after 6 h in Swiss and C57B1/6J mice, but was absent in Bk2r(-/-) mice. In the presence of cycloheximide, des-Arg9-bradykinin did not cause any response at 6 h. 3. Similar findings were obtained in the urinary bladder: at 1 h des-Arg9-bradykinin (1 microM) did not cause any motor effect, whereas at 6 h it caused a contraction that was 28-59% of that produced by carbachol (1 microM) in the three mouse strains. Cycloheximide blocked the response to des-Arg9-bradykinin. Bradykinin (1 microM) contracted urinary bladders at 1 h (34-35% of carbachol), as well as at 6 h (66-77% of carbachol) in Swiss and C57B1/6J strains, but was without effect in Bk2r(-/-) mice. 4. Northern blot hybridization with a specific cDNA probe against mouse B1 receptor mRNA using total RNA extracted from tracheae and urinary bladders freshly removed from Swiss and Bk2r(-/-) mice revealed minimal expression. However, marked hybridization was detected 150 min after in vitro exposure in both tissues. 5. Evidence is provided that in vitro exposure of mouse trachea and urinary bladder causes a time-dependent induction of B1 receptors that cause relaxation and contraction, respectively.  相似文献   
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