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81.
Macdonald D Murgolo N Zhang R Durkin JP Yao X Strader CD Graziano MP 《Molecular pharmacology》2000,58(1):217-225
A molecular model of the human melanin-concentrating hormone (MCH) peptide was constructed and docked into a helical, bacteriorhodopsin-based model of the recently identified human MCH receptor. From this hormone-receptor complex, potential sites of agonist-receptor interaction were identified, and site-directed mutagenesis was used to substitute residues predicted to reside within the receptor binding pocket. Substitution of Asp(123)(3.32) in the third transmembrane domain of the receptor resulted in a loss of detectable (125)I-MCH binding and of MCH-stimulated Ca(2+) flux; cell surface expression of the mutant receptor was not affected. Arg(11) and Arg(14) of the MCH ligand were identified as potential sites of interaction with Asp(123)(3.32). [Ala(14)]-MCH was equipotent to native MCH in its ability to bind to and activate the wild-type MCH receptor, whereas [Ala(11)]-MCH displayed a 3000-fold reduction in binding affinity and a complete loss of measurable functional activity. Furthermore, [Lys(11)]-MCH and [D-Arg(11)]-MCH displayed reduced affinity for the receptor. [Lys(11)]-MCH was observed to be a partial agonist, eliciting approximately 67% of the native peptide's activity in a Ca(2+) flux assay, and [D-Arg(11)]-MCH was determined to be a functional antagonist with a K(b) valve of 15.8 microM. These data provide evidence that a basic moiety with specific stereochemical requirements at this site is needed for receptor activation. We conclude that both Asp(123)(3.32) in the MCH receptor and Arg(11) in the MCH peptide are required for the formation of the MCH peptide/receptor complex and propose that they form a direct interaction that is critical for receptor function. 相似文献
82.
Identification of kaempferol as a monoamine oxidase inhibitor and potential Neuroprotectant in extracts of Ginkgo biloba leaves 总被引:5,自引:0,他引:5
Sloley BD Urichuk LJ Morley P Durkin J Shan JJ Pang PK Coutts RT 《The Journal of pharmacy and pharmacology》2000,52(4):451-459
The effects of Ginkgo biloba leaf extract on rat brain or livermonoamine oxidase (MAO)-A and -B activity, biogenic amine concentration in nervous tissue, N-methyl-D-aspartate (NMDA)- and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)-induced neurotoxicity and antioxidant activity was investigated to determine the effects of the extract on monoamine catabolism and neuroprotection. Ginkgo biloba leaf extract was shown to produce in-vitro inhibition of rat brain MAO-A and -B. The Ginkgo biloba extract was chromatographed on a reverse-phase HPLC system and two of the components isolated were shown to be MAO inhibitors (MAOIs). These MAOIs were identified by high-resolution mass spectrometry as kaempferol and isorhamnetin. Pure kaempferol and a number of related flavonoids were examined as MAOIs in-vitro. Kaempferol, apigenin and chrysin proved to be potent MAOIs, but produced more pronounced inhibition of MAO-A than MAO-B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO-A were 7 x 10(-7), 1 x 10(-6) and 2 x 10(-6) M, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex-vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Kaempferol was shown to protect against NMDA-induced neuronal toxicity in-vitro in rat cortical cultures, but did not prevent DSP-4-induced noradrenergic neurotoxicity in an in-vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid-peroxidation assay. This data indicates that the MAO-inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability. 相似文献
83.
84.
Kevin Durkin Andrew Whitehouse Emma Jaquet Kathy Ziatas Allan J. Walker 《Research in autism spectrum disorders》2010,4(2):314-318
While young people have generally been at the forefront of the adoption and use of new communications technologies, little is known of uses by exceptional youth. This study compares cell phone use by a group of adolescents with Asperger Syndrome (n = 35) with that by a group of adolescents with typical development (n = 35). People with Asperger Syndrome tend to have limited ability to take part in reciprocal communication and weaker social motivation. We predicted that this group would be less likely to have access to cell phones and, if they did have them, would be less likely to use them for talking to peers and more likely to use non-communicative features, such as games. These predictions received strong support. The findings have implications for theoretical accounts of new media use by the young, for our knowledge of the lives of individuals with AS, and for caregivers of children with exceptional conditions. 相似文献
85.
Radiologically guided balloon catheters were used to dilate 94 gastrointestinal strictures in 92 patients over a 6-year period. Fifty strictures were esophageal and 44 nonesophageal (22 gastroenterostomies, 11 antral-pyloric strictures, four colorectal strictures, four enteroenterostomies, and three miscellaneous strictures). Factors influencing the success of stricture intubation included patient age, stricture location (esophageal vs. nonesophageal and proximal vs. distal esophageal), and association with a surgical anastomosis. Malignancy was associated with greater postdilation irregularity and a smaller increase in stricture diameter, as measured radiographically. Procedural failures occurred in 8% of cases (2% of esophageal and 30% of nonesophageal lesions). Two small, asymptomatic mucosal tears were seen after dilation (one esophageal and one colonic); no other procedural complications occurred. Following successful dilation, 16 patients (17%; six with esophageal and ten with non-esophageal strictures) had recurrence of symptoms during short-term (30-day) follow-up. 相似文献
86.
87.
A retrospective review of congenital cleft foot was done on 16 patients with 32 involved feet. The average age at the time of surgery was 4 years (range, 5 months to 13 years). The average follow-up after surgery was 7.8 years, with a range of 2-45 years. A simple classification based on severity of deficiency was developed. Twenty-three of the 24 procedures performed gave a satisfactory result. Six of the nine untreated feet were satisfactory. Based on our classification, the following treatment is recommended: type I, central partial forefoot cleft was treated by a soft-tissue syndactylism and a partial hallux valgus correction, if needed. Type II, for a complete forefoot cleft to the tarsus, soft-tissue syndactylism with first-ray osteotomy if necessary before age 5 years is recommended. First-ray amputation is advised after age 5 years. Type III: Complete absence of first through fourth ray did not need forefoot surgery. 相似文献
88.
Artioli Silvana Schellini Shane R Durkin Erika Hoyama Flavio Hirai Ricardo Cordeiro Robert J Casson Dinesh Selva Carlos Roberto Padovani 《BMC ophthalmology》2009,9(1):8-9
Background
This paper reports population-based data on the prevalence and causes of visual impairment among children and adults in Botucatu, Brazil. 相似文献89.
90.
SG Hannover 《MedR Medizinrecht》2002,20(6):319-320
Ohne Zusammenfassung 相似文献