Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triph...Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures.He La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR structures.In He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS mixed.Ribavirin and MPA treatments induced only IMPDH2-based RR.Cells were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 construct.Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR.These results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.展开更多
背景:急性缺血性脑卒中是各种原因导致的脑组织血液供应障碍,并由此产生缺血缺氧性坏死,进而出现神经功能障碍的一组临床综合征。方法:进行前瞻性随机对照临床试验,病例来源于乌鲁木齐市友谊医院急诊科就诊的前循环AIS患者。采用16 cm宽...背景:急性缺血性脑卒中是各种原因导致的脑组织血液供应障碍,并由此产生缺血缺氧性坏死,进而出现神经功能障碍的一组临床综合征。方法:进行前瞻性随机对照临床试验,病例来源于乌鲁木齐市友谊医院急诊科就诊的前循环AIS患者。采用16 cm宽体CT (Revolution CT, GE, USA)进行扫描,图像后处理。通过ASPECTS评分方法,CTP各参数的计算方法,常规mCTA软脑膜侧枝评分进行影像评估。由两名经验丰富的放射科医生,在不知道患者临床结果及临床评分的情况下,间隔一定时间,将患者各种图像进行评分。对主要结局指标及随访指标进行数据分析。结果:AIS患者得到的图像质量良好,并请影像科及神经内科医生按课题设计的研究方法进行阅片,阅片的结果比较接近:ColorVizmCTA图像的解读较常规mCTA、CTP图像更简单、直观、迅速、可操作性强,对医生的基础及背景要求不高,而且大部分医生的诊断一致性好。用ColorVizmCTA图像诊断结果与用常规mCTA、CTP诊断的结果一致性较好。结论:ColorVizmCTA图像的解读较常规mCTA、CTP图像更简单、直观、迅速、可操作性强。ColorViz mCTA对于前循环AIS患者的侧枝循环的评价效能与常规mCTA具有良好的一致性,对患者最终梗死体积的预测与CTP参数的评估一致性良好。Background: Acute ischemic stroke is a group of clinical syndromes in which the blood supply of brain tissue is impaired due to various causes, which leads to hypoxic-ischemic necrosis, and then neurological dysfunction. Methods: A prospective randomized controlled clinical trial was conducted. Patients with anterior circulation AIS were recruited from the emergency department of Urumqi Friendship Hospital. Scanning was performed on a 16 cm wide-body CT (Revolution CT, GE, USA), and the images were post-processed. The ASPECTS score method, CTP parameter calculation method, and conventional mCTA leptomeningeal collateral score were used for imaging evaluation. The images of the patients were scored by two experienced radiologists at a certain interval without knowing the clinical results and clinical scores of the patients. The primary outcome indicators and follow-up indicators were analyzed. Results: The quality of the images obtained from AIS patients was good, and the results were similar when the images were read by radiologists and neurologists according to the study design. The interpretation of ColorViz mCTA images is simpler, more intuitive, faster and more operable than conventional mCTA and CTP images. It does not require high basic and background requirements for doctors, and most doctors have good diagnostic consistency. The diagnostic results of ColorViz mCTA images were consistent with those of conventional mCTA and CTP images. Conclusion: ColorViz mCTA image interpretation is simpler, more intuitive, faster and more maneuverable than conventional mCTA and CTP images. ColorViz mCTA is in good agreement with conventional mCTA in evaluating the collateral circulation of patients with anterior circulation AIS. The prediction of the final infarct volume of patients is in good agreement with the evaluation of CTP parameters.展开更多
基金supported by the Brazilian Government Research Foundation CAPES (Coordination for the Improvement of Higher Education Personnel,No.9028-11-0)the Sao Paulo State Research Foundation (Sao Paulo Government agency FAPESP,No.2011/12448-0)both granted to LECA and GDK,and by the research grant from Brazilian Government Agency CNPq (No.305064/2011-8) to LECA
文摘Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures.He La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR structures.In He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS mixed.Ribavirin and MPA treatments induced only IMPDH2-based RR.Cells were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 construct.Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR.These results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.
文摘背景:急性缺血性脑卒中是各种原因导致的脑组织血液供应障碍,并由此产生缺血缺氧性坏死,进而出现神经功能障碍的一组临床综合征。方法:进行前瞻性随机对照临床试验,病例来源于乌鲁木齐市友谊医院急诊科就诊的前循环AIS患者。采用16 cm宽体CT (Revolution CT, GE, USA)进行扫描,图像后处理。通过ASPECTS评分方法,CTP各参数的计算方法,常规mCTA软脑膜侧枝评分进行影像评估。由两名经验丰富的放射科医生,在不知道患者临床结果及临床评分的情况下,间隔一定时间,将患者各种图像进行评分。对主要结局指标及随访指标进行数据分析。结果:AIS患者得到的图像质量良好,并请影像科及神经内科医生按课题设计的研究方法进行阅片,阅片的结果比较接近:ColorVizmCTA图像的解读较常规mCTA、CTP图像更简单、直观、迅速、可操作性强,对医生的基础及背景要求不高,而且大部分医生的诊断一致性好。用ColorVizmCTA图像诊断结果与用常规mCTA、CTP诊断的结果一致性较好。结论:ColorVizmCTA图像的解读较常规mCTA、CTP图像更简单、直观、迅速、可操作性强。ColorViz mCTA对于前循环AIS患者的侧枝循环的评价效能与常规mCTA具有良好的一致性,对患者最终梗死体积的预测与CTP参数的评估一致性良好。Background: Acute ischemic stroke is a group of clinical syndromes in which the blood supply of brain tissue is impaired due to various causes, which leads to hypoxic-ischemic necrosis, and then neurological dysfunction. Methods: A prospective randomized controlled clinical trial was conducted. Patients with anterior circulation AIS were recruited from the emergency department of Urumqi Friendship Hospital. Scanning was performed on a 16 cm wide-body CT (Revolution CT, GE, USA), and the images were post-processed. The ASPECTS score method, CTP parameter calculation method, and conventional mCTA leptomeningeal collateral score were used for imaging evaluation. The images of the patients were scored by two experienced radiologists at a certain interval without knowing the clinical results and clinical scores of the patients. The primary outcome indicators and follow-up indicators were analyzed. Results: The quality of the images obtained from AIS patients was good, and the results were similar when the images were read by radiologists and neurologists according to the study design. The interpretation of ColorViz mCTA images is simpler, more intuitive, faster and more operable than conventional mCTA and CTP images. It does not require high basic and background requirements for doctors, and most doctors have good diagnostic consistency. The diagnostic results of ColorViz mCTA images were consistent with those of conventional mCTA and CTP images. Conclusion: ColorViz mCTA image interpretation is simpler, more intuitive, faster and more maneuverable than conventional mCTA and CTP images. ColorViz mCTA is in good agreement with conventional mCTA in evaluating the collateral circulation of patients with anterior circulation AIS. The prediction of the final infarct volume of patients is in good agreement with the evaluation of CTP parameters.
