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991.
K Salchow ME Bond SC Evans NJ Press SJ Charlton PA Hunt ME Bradley 《British journal of pharmacology》2010,159(7):1429-1439
Background and purpose:
We have previously shown that SB265610 (1-(2-bromo-phenyl)-3-(7-cyano-3H-benzotriazol-4-yl)-urea) behaves as an allosteric, inverse agonist at the C-X-C chemokine (CXCR)2 receptor. The aim of this study was to determine whether SB265610, in addition to two other known antagonists, bind to either of the two putative, topographically distinct, allosteric binding sites previously reported in the Literature.Experimental approach:
Ten single point mutations were introduced into the CXCR2 receptor using site-directed mutagenesis. Three CXCR2 antagonists were investigated, SB265610, Pteridone-1 (2-(2,3 difluoro-benzylsulphanyl)-4-((R)-2-hydroxy-1-methyl-ethylamino)-8H-pteridin-7-one) and Sch527123 (2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5-methyl-furan-2-yl)-propyl]amino]-3,4-dioxo-cyclobut-1enylamino}-benzamide), and the effect of these mutations on their binding affinity and ability to inhibit interleukin-8-stimulated binding of [35S]GTPγS was examined.Key results:
Seven of the nine mutations introduced into the C-terminal domain and intracellular loops of the receptor produced a significant reduction in affinity at least one of the antagonists tested. Of those seven mutations, three produced a significant reduction in the affinity of all three antagonists, namely K320A, Y314A and D84N. In all but one mutation, the changes observed on antagonist affinity were matched with effects on inhibition of interleukin-8-stimulated [35S]GTPγS binding.Conclusions and implications:
These antagonists bind to a common intracellular, allosteric, binding site of the CXCR2 receptor, which has been further delineated. As many of these mutations are close to the site of G protein coupling or to a region of the receptor that is responsible for the transduction of the activation signal, our results suggest a molecular mechanism for the inhibition of receptor activation. 相似文献992.
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The authors present the case report of a patient in whom hypopituitarism, diplopia, and visual field defects were due to eosinophilic granuloma. Radiographic studies were suggestive of a pituitary tumor and subsequent histological evaluation showed replacement of the anterior pituitary by histiocytic cells. Eosinophilic granuloma should be included in the differential diagnosis of an intrasellar mass. 相似文献
995.
ME HIBBERT C HAMILL M ROSIER J CAUST G PATTON G BOWES 《Journal of paediatrics and child health》1996,32(5):372-377
Objective : To examine the utility of notebook computers in the collection of data in large scale surveys.
Methodology : A notebook computer administered survey of health in adolescents was conducted in 1992 using a multi-instrument questionnaire. Students in school years 7,9 and 11 in private and government schools in Melbourne and rural Victoria participated.
Results : Parental consent was obtained with an 83% response rate. Each student answered questions directly onto the computer taking an average of 68 min to complete the highly branched confidential but not anonymous questionnaire. Students were presented with on average 33% of the 897 possible questions. Over 90% of students reported enjoying using the computer. Those who reported answering the questions honestly all the time ranged from 68 to 85%, increasing with grade level.
Conclusions : The use of computers in survey research provides many advantages in data collection including exposure only to relevant questions and the opportunity of asking sensitive questions. 相似文献
Methodology : A notebook computer administered survey of health in adolescents was conducted in 1992 using a multi-instrument questionnaire. Students in school years 7,9 and 11 in private and government schools in Melbourne and rural Victoria participated.
Results : Parental consent was obtained with an 83% response rate. Each student answered questions directly onto the computer taking an average of 68 min to complete the highly branched confidential but not anonymous questionnaire. Students were presented with on average 33% of the 897 possible questions. Over 90% of students reported enjoying using the computer. Those who reported answering the questions honestly all the time ranged from 68 to 85%, increasing with grade level.
Conclusions : The use of computers in survey research provides many advantages in data collection including exposure only to relevant questions and the opportunity of asking sensitive questions. 相似文献
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The importance of age of the recipient (uterine age) with regards to
pregnancy rate, delivery rate and miscarriage rate following oocyte
donation was evaluated using retrospective data analysis of cases where two
recipients from different age groups shared oocytes from a single donor and
had equal numbers of embryos transferred. A total of 104 women (21-52 years
of age) underwent a total of 104 cycles of oocyte donation. They were
divided into groups according to age (group A: age 39 years or less and
group B: age between 40 and 52 years). The minimum age difference between a
pair of recipients was five years. Hormone replacement therapy (HRT) was
given using oestradiol valerate (6 mg daily) for at least 10 days, followed
by a combination of oestradiol with either intramuscular progesterone (100
mg daily), or vaginally administered micronized progesterone (300 microg
daily). Women with ovarian function received down-regulation using a
luteinizing hormone- releasing hormone (LHRH) analogue before hormone
replacement was commenced. A total of 52 transfer cycles was performed in
each age group and pregnancy, delivery and miscarriage rates were analysed
as outcome measures; 20 pregnancies were achieved in each group (an
identical pregnancy rate of 38.5%). In group A seven pregnancies miscarried
out of 20 (35%), which was not significantly different from the rate in the
older population, group B, where eight out of 20 pregnancies miscarried
(40%). The delivery rate in group A was 25% (13 out of 52), again not
significantly different from the delivery rate in group B of 23.1% (12 out
of 52). In conclusion, using egg donation as a model, the decline in
fecundity with age cannot be explained by uterine factors alone.
相似文献
999.
NUMANS ME; VAN DER GRAFF Y; DE WIT NJ; TOUW-OTTEN FWMM; DE MELKER RA 《Family practice》1994,11(4):382-388
A cross-sectional diagnostic prevalence study was carried outwithin a multi-centre experiment with open access gastroscopyin Utrecht, The Netherlands. The objective of the study wasto contribute to improvement of patient selection for open accessgastroscopy and to evaluate diagnostic determinants for pepticulcer. Data were analysed in all 861 patients who were consecutivelynewly referred during the experiment to undergo gastroscopy.Patient characteristics and outcomes of gastroscopies were recorded.Univariate and multivariate (logistic) analyses were carriedout and the results were evaluated with ROC (receiver operatingcharacteristic) analysis. The most important clinical characteristicsto be used for prediction of peptic ulcer are pain on an emptystomach, absence of pain after a meal and absence of obstructivecomplaints. The scoring list derived from the full model, comprisingthese characteristics together with age, sex, information onformer dyspeptic diseases, medication and smoking (basiccharacteristics), predicted peptic ulcer with an AUCof 0.78. The ulcer-like model, with characteristicsknown from the literature, had an AUC of 0.76. The amount ofgastroscopy requests on patients suspected of a peptic ulcercould have been reduced from 60 to 44%. Forcing basiccharacteristics into scoring lists on peptic ulcer improvedthe pre-diagnostic test capacities. The presented scoring listmay improve gastroscopy requesting by GPs aiming at findingpeptic ulcers. Practical manageability of the list should beprospectively evaluated in future experiments. 相似文献
1000.