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231.
This year's 40th season of Keystone symposia meetings was held in Banff, Alberta, Canada, on February 11-16 and sponsored by Astellas Pharma and Regulus Therapeutics. The meeting was organized by Gregory Hannon, Curtis Harris, and Martine Roussel and centered on microRNAs (miRNA), noncoding RNAs, and cancer. The meeting was grouped around the following topical areas: miRNA mechanisms, oncogenesis, immune response, angiogenesis and metastasis, cancer biomarkers, stem cells, and therapeutics. This report highlights findings and concepts presented during this meeting. 相似文献
232.
We report the clinical, cytogenetic, and molecular data of two patients diagnosed with acute lymphoblastic leukemia characterized by the rare translocation t(12;17)(p13;q12). This translocation has been reported in 25 cases and its putative molecular consequence, the formation of a TAF15-ZNF384 fusion gene, in only six cases. We used fluorescence in situ hybridization followed by long-range polymerase chain reaction to find the translocation breakpoints. A fusion between TAF15 and ZNF384 was identified and confirmed by nucleotide sequencing. Our results confirm that the t(12;17)(p13;q12) leading to a TAF15-ZNF384 fusion gene characterizes a specific subgroup of acute lymphoblastic leukemia and suggest that two different breakpoints in TAF15 may be involved. Whether the two variants of the TAF15-ZNF384 fusion that these correspond to are in any way hematologically or prognostically different, is unknown. 相似文献
233.
Sokołowska P Urbańska A Namiecińska M Biegańska K Zawilska JB 《Neuroscience letters》2012,506(2):303-306
Orexin A and B (hypocretin-1 and -2) are hypothalamic peptides that exert their biological functions by stimulation of two specific, membrane-bound receptors, OX1R and OX2R. Recently, we have demonstrated the expression of both types of orexin receptors in rat cortical neurons, with the OX2R level being markedly higher compared to OX1R. In the present study we investigated the receptor-mediated effects of orexin A, an agonist of OX1R and OX2 R, orexin B and [Ala11-D-Leu15]orexin B, preferential agonists of OX2R, on survival of cultured neurons derived from rat cerebral cortex. The three tested peptides markedly increased neuronal viability in a concentration-dependent manner. The pro-survival properties of orexins were associated with an attenuation of caspase-3 activity. Comparable potency of orexin A, orexin B and [Ala11-D-Leu15]orexin B suggests a predominant role of OX2R in the studied phenomenon. Our findings provide new insights into the role of orexins in CNS as potential neuroprotective factors. 相似文献
234.
Catalano R Margerison-Zilko CE Saxton K LeWinn K Anderson E 《Social science & medicine (1982)》2011,72(6):1016-7; discussion 1018-20
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236.
Woldan-Tambor A Biegańska K Wiktorowska-Owczarek A Zawilska JB 《Pharmacological reports : PR》2011,63(3):717-723
The effects of orexins, which are also named hypocretins, on cAMP formation were examined in primary cultures of rat astrocytes. Orexin A, an agonist of OX1 and OX2 receptors, stimulated cAMP production with an EC50 value of 0.68 µM and potentiated the forskolin-induced increase in the nucleotide synthesis. [Ala11-D-Leu15]orexin B, an agonist of OX2 receptors, was inactive. The effects of orexin A were antagonized by SB 408124, a selective blocker of OX1 receptors, but were not affected by TCS OX2 29, a selective antagonist of OX2 receptors. We hypothesized that the activation of OX1 receptors stimulated cAMP synthesis in primary rat astrocyte cultures. 相似文献
237.
Burroughs SL Duncan RS Rayudu P Kandula P Payne AJ Clark JL Koulen P Kaja S 《Journal of neuroscience methods》2012,203(1):141-145
Drug discovery and development efforts critically rely on cell-based assays for high-throughput screening. These assay systems mostly utilize immortalized cell lines, such as human embryonic kidney cells, and can provide information on cytotoxicity and cell viability, permeability and uptake of compounds as well as receptor pharmacology. While this approach has proven extremely useful for single-target pharmacology, there is an urgent need for neuropharmacological studies to screen novel drug candidates in a cellular environment resembles neurons in vivo more closely, in order to gain insight into the involvement of multiple signaling pathways. Primary cultured neuronal cells, such as cortical neurons, have long been used for basic research and low-throughput screening and assay development, and may thus be suitable candidates for the development of neuropharmacological high-throughput screening approaches. We here developed and optimized protocols for the use of primary cortical neuronal cells in high-throughput assays for neuropharmacology and neuroprotection, including calcium mobilization, cytotoxicity and viability as well as ion channel pharmacology. Our data show low inter-experimental variability and similar reproducibility as conventional cell line assays. We conclude that primary neuronal cultures provide a viable alternative to cell lines in high-throughput assay systems by providing a cellular environment more closely resembling physiological conditions in the central nervous system. 相似文献
238.
Kristoffersen AH Thue G Ajzner E Claes N Horvath AR Leonetti R Kallion K Kitchen D Kitchen S Kutt M Meijer P Muller M Nilsson E Perich C Plum I Rogic D Tirimacco R van der Meer FJ Watine J Sandberg S 《Thrombosis research》2012,130(3):309-315
Introduction
Standardisation of treatment with vitamin K antagonists (VKAs) is still an issue after 60 years of use. The study aimed to explore aspects of VKA monitoring in primary and secondary care.Methods
Two case histories were distributed to physicians in 13 countries. Case history A focused on a patient with atrial fibrillation on stable anticoagulation (latest INR 2.3). Physicians were asked about frequency of INR measurement, when to change the VKA dose, and the patient's annual risk of ischemic stroke and bleeding. Case history B focused on a patient with an unexpected INR of 4.8, asking for the patient's 48-hour bleeding risk, the immediate dose reduction and time until a repeat INR.Results
Altogether, 3016 physicians responded (response rate 8 - 38%), of which 82% were from primary care and 18% from secondary care. Answers varied substantially within and between countries regardless of level of care and VKA used. Median number of weeks between INR measurements was 4 - 6 weeks. Median threshold INR for increasing or decreasing the VKA dose was 1.9 and 3.1, respectively. Risk of ischemic stroke and bleeding were overestimated 2 - 3 times. In case history B, the median dose reduction the two first days was 75% for GPs and 55% for specialists, irrespective of estimates of bleeding risk; with one week to a repeat INR.Conclusion
Variation in VKA monitoring is substantial implying clinical consequences. Guidelines seem either unknown or may be considered impracticable. Further efforts towards standardisation of VKA management are needed. 相似文献239.
Magnhild Kverneland Karl Otto Nakken Dag Hofoss Annette Holth Skogan Per Ole Iversen Kaja Kristine Selmer Morten Ingvar Lossius 《Epilepsia》2023,64(5):e69-e74
Ketogenic diet, a high-fat, low-carbohydrate diet, is an established treatment for patients with severe epilepsy. We have previously reported a moderate reduction in seizure frequency after treatment with a modified Atkins diet. This study aimed to see whether dietary therapy impacts patients' health-related quality of life (HRQOL). In a randomized controlled design, we compared the change in self-reported HRQOL among adults with difficult-to-treat epilepsy after a 12-week diet intervention. Thirty-nine patients with drug-resistant focal epilepsy (age = 16–65 years) were randomized to eat a modified Atkins diet with maximum 16 g of carbohydrate per day (diet group, n = 19) or to continue eating habitual diet (control group, n = 20). No changes to the other epilepsy treatments were allowed. Patient-reported HRQOL was assessed with the Quality of Life in Epilepsy Inventory-89 (QOLIE-89). The diet group experienced a statistically significant improvement in mean total score of QOLIE-89 of 10 points compared to controls (p = .002). Moreover, although not statistically significant when using a cutoff of 50% seizure reduction, our data suggest an association between diet-induced reduction in seizure frequency and improvement in HRQOL. The improvement in HRQOL was not associated with diet-induced weight reduction. 相似文献
240.