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801.
X Zhang T YY Lai S WY Chiang P OS Tam D TL Liu C KM Chan C P Pang C Zhao L J Chen 《Eye (London, England)》2013,27(10):1204-1213
Purpose
Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients.Methods
Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12–16, 22–32, and 38–45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses.Results
Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study.Conclusions
Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP. 相似文献802.
803.
The peripheral dose outside the applicators in electron beams was studied using a Varian 21 EX linear accelerator. To measure the peripheral dose profiles and point doses for the applicator, a solid water phantom was used with calibrated Kodak TL films. Peak dose spot was observed in the 4 MeV beam outside the applicator. The peripheral dose peak was very small in the 6 MeV beam and was ignorable at higher energies. Using the 10 x 10 cm(2) cutout and applicator, the dose peak for the 4 MeV beam was about 12 cm away from the field central beam axis (CAX) and the peripheral dose profiles did not change with depths measured at 0.2, 0.5 and 1 cm. The peripheral doses and profiles were further measured by varying the angle of obliquity, cutout and applicator size for the 4 MeV beam. The local peak dose was increased with about 3% per degree angle of obliquity, and was about 1% of the prescribed dose (angle of obliquity equals zero) at 1 cm depth in the phantom using the 10 x 10 cm(2) cutout and applicator. The peak dose position was also shifted 7 mm towards the CAX when the angle of obliquity was increased from 0 to 15 degrees. 相似文献
804.
CE Beyer Q Lin B Platt J Malberg G Hornby KM Sullivan DL Smith T Lock PJ Mitchell NT Hatzenbuhler DA Evrard BL Harrison R Magolda MN Pangalos LE Schechter S Rosenzweig-Lipson TH Andree 《British journal of pharmacology》2009,157(2):307-319
Background and purpose
As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT1A receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT1A receptor antagonist activities, was evaluated in preclinical models.Experimental approach
Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models.Key results
WAY-211612 inhibited 5-HT reuptake (Ki = 1.5 nmol·L−1; KB = 17.7 nmol·L−1) and exhibited full 5-HT1A receptor antagonist activity (Ki = 1.2 nmol·L−1; KB = 6.3 nmol·L−1; Imax 100% in adenyl cyclase assays; KB = 19.8 nmol·L−1; Imax 100% in GTPγS). WAY-211612 (3 and 30 mg·kg−1, po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT1A receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3–30 mg·kg−1, po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg·kg−1, s.c.) and a 5-HT1A antagonist (WAY-100635; 0.3 mg·kg−1, s.c). WAY-211612 (3.3–30 mg·kg−1, s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3–30 mg·kg−1, i.p. and 10–56 mg·kg−1, po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg·kg−1, i.p.) in the rat scheduled-induced polydipsia model.Conclusions and implications
These findings suggest that WAY-211612 may represent a novel antidepressant. 相似文献805.
Background
Nasal modes of respiratory support cause variable amounts of gastric dilatation which may increase gastro-oesophageal reflux (GER) in preterms. To compare the incidence of GER in nasally ventilated, preterm babies with controls (babies not on ventilation). Type of study: A prospective, observational comparative study.Method
Twenty-three preterm babies of gestational age 28–36 weeks and weight ranging between 1,000 g and < 2,500 g on either nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure venti-lation (nIPPV) were assessed for GER. They were compared with controls not on ventilation some of who were test babies when off ventilation (subgroup A) and some were unrelated babies not on ventilator but matched for gestational age and weight with test babies (subgroup B). All babies were subjected to continuous, oesophageal pH monitoring with dual sensor (upper and lower oesophageal) catheters. Reflux index (RI) was calculated as the percentage of study time the lower oesophageal pH was < 4. Primary outcome was the RI in the test and controls groups. Secondary outcome was the temporal relation of the reflux with symptoms if any. Numerical data were shown as mean with standard deviation and statistical comparisons were done using the χ2-test, Fischer test, and t-test wherever applicable.Results
The RI was higher in ventilated babies as compared to the control group, particularly in the subgroup A, where test babies formed their own controls. Grade IV reflux (7 cases) was seen only in the ventilated babies. There was no difference in the incidence of GER in babies on nCPAP as compared with nIPPV. Grade IV reflux could not be reliably predicted by RI alone. No definite temporal relation between episodes of reflux and symptoms could be determined in this study.Conclusion
There is an increase in GER in preterms on nasal modes of ventilation. A combination of upper (pharyngeal) and lower oesophageal sensors are preferred to a single lower oesophageal sensor when assessing GER by oesophageal pHmetry in neonates. 相似文献806.
807.