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排序方式: 共有2958条查询结果,搜索用时 406 毫秒
91.
92.
Elmeri M. Jokinen Pekka A. Postila Mira Ahinko Sanna Niinivehmas Olli T. Pentikinen 《Chemical biology & drug design》2019,94(4):1799-1812
A novel virtual screening methodology called fragment‐ and negative image‐based (F‐NiB) screening is introduced and tested experimentally using phosphodiesterase 10A (PDE10A) as a case study. Potent PDE10A‐specific small‐molecule inhibitors are actively sought after for their antipsychotic and neuroprotective effects. The F‐NiB combines features from both fragment‐based drug discovery and negative image‐based (NIB) screening methodologies to facilitate rational drug discovery. The selected structural parts of protein‐bound ligand(s) are seamlessly combined with the negative image of the target's ligand‐binding cavity. This cavity‐ and fragment‐based hybrid model, namely its shape and electrostatics, is used directly in the rigid docking of ab initio generated ligand 3D conformers. In total, 14 compounds were acquired using the F‐NiB methodology, 3D quantitative structure–activity relationship modeling, and pharmacophore modeling. Three of the small molecules inhibited PDE10A at ~27 to ~67 μM range in a radiometric assay. In a larger context, the study shows that the F‐NiB provides a flexible way to incorporate small‐molecule fragments into the drug discovery. 相似文献
93.
Anne‐Maree Kelly Oene Van Meer Gerben Keijzers Justina Motiejunaite Peter Jones Richard Body Simon Craig Mehmet Karamercan Sharon Klim Veli‐Pekka Harjola Franck Verschuren Anna Holdgate Michael Christ Adela Golea Colin A. Graham Jean Capsec Cinzia Barletta Luis Garcia‐Castrillo Win S. Kuan Said Laribi 《Internal medicine journal》2020,50(2):200-208
94.
Kim Fejgin Jacob Nielsen Michelle R. Birknow Jesper F. Bastlund Vibeke Nielsen Jes B. Lauridsen Hreinn Stefansson Stacy Steinberg Helge B.D. Sorensen Troels E. Mortensen Peter H. Larsen Ib V. Klewe Søren V. Rasmussen Kari Stefansson Thomas M. Werge Pekka Kallunki Kenneth V. Christensen Michael Didriksen 《Neuropsychopharmacology》2014
95.
Objective : To resolve if TBX22 mutations cause isolated tongue-tie in the Finnish population. Design : Mutation analysis of the coding region of the TBX22 gene in 50 Finnish isolated tongue-tie patients and 61 control samples. Results : One putative sequence variation was identified from two male patients, but whether this represents a polymorphism or causative mutation remains unknown. Conclusions : Mutations in the coding region of the TBX22 gene are not a major cause of ankyloglossia in the Finnish population and do not explain the sex difference or inheritance of tongue-tie. 相似文献
96.
Missing a canine is of serious concern in social life of a patient in most of societies. While conventional fixed partial dentures and implant-supported restorations may often be the treatment of choice, fiber-reinforced composite (FRC) resins offer a conservative, fast and cost-effective alternative for single and multiple teeth replacement. This clinical report presents two cases where FRC technology was successfully used to restore canine edentulous area in terms of esthetic-cosmetic values and functionality. 相似文献
97.
Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19% improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity, and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for Rps19-deficient hematopoiesis and was associated with down-regulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA. 相似文献
98.
Ukkola A Mäki M Kurppa K Collin P Huhtala H Kekkonen L Kaukinen K 《European Journal of Internal Medicine》2012,23(4):384-388
ObjectiveThe clinical presentation of coeliac disease has changed and patients are often overweight at diagnosis. There is concern that patients might gain further weight while on a gluten-free diet (GFD). The aim of the study was to evaluate the impact of a GFD on the body mass index (BMI) in a nationwide cohort of coeliac patients and to determine variables predictive of favourable or unfavourable BMI changes.MethodsWe prospectively investigated weight and disease-related issues in 698 newly detected adults diagnosed due to classical or extraintestinal symptoms or by screening. BMI at diagnosis and after one year on a GFD were assessed and compared with that in the general population.ResultsAt diagnosis, 4% of subjects were underweight, 57% normal, 28% overweight and 11% obese. On a GFD, 69% of underweight patients gained and 18% of overweight and 42% of obese lost weight; in the rest BMI remained stable. Changes were similar in both symptom- and screen-detected patients. The coeliac group had a more favourable BMI pattern than the general population. Favourable BMI changes were associated with subjects' self-rated expertise on GFD and young age at diagnosis, but not dietary counselling received.ConclusionsBMI improved similarly in screen- and symptom-detected coeliac disease patients on a GFD. 相似文献
99.
100.
Matti Pokela Ville Jäntti Pasi Lepola Pekka Romsi Jussi Rimpiläinen Kai Kiviluoma 《Scandinavian cardiovascular journal : SCJ》2013,47(3):154-157
Objective--To evaluate whether electroencephalography (EEG) recovery could be considered a reliable marker of brain injury after experimental hypothermic circulatory arrest (HCA). Design--Cortical electrical activity was registered before and after a 75-min period of HCA in 27 pigs that survived 7 days after the experiment. The sum of EEG bursts was counted as a percentage of the sum of artifact-free bursts and suppressions, and this percentage was used as a measure of EEG activity in the analysis. Results--Brain infarction developed in 13 animals (48.1%), in 12 cases (44.4%) having involved the cortex, in 1 case the thalamus (3.7%) and in another the hippocampus (3.7%). The mean EEG burst percentage significantly correlated with the total brain histopathological score (ρ?=??0.588, P?=?0.001). EEG burst percentage from the 2?h 20?min to the 7?h 20?min interval correlated with the total brain histopathological score and with the cortex, brainstem and cerebellum scores. The mean EEG burst percentage rate was higher, but not significantly, among the animals without brain infarction (38.5% vs 32.4%), but such a difference was significant at the 3?h 20?min postoperative interval (P?=?0.02). The mean EEG burst percentage significantly correlated with brain glucose concentration at the 1?h interval (ρ?=?0.387; P?=?0.046), brain lactate concentration at the 2?h interval (ρ?=??0.431; P?=?0.025), and the brain lactate/glucose ratio at the 1?h 30?min interval from the start of rewarming (ρ?=??0.433; P?=?0.024). Conclusion--A decreased EEG burst percentage seems to be associated with an increased risk of developing histologically evident brain ischemic injury in the cortex, brainstem and cerebellum after experimental HCA. 相似文献