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991.
Connie J. Chen Stuart Kaufman Kirk Packo Heidi Stöhr Bernhard H. F. Weber Morton F. Goldberg 《Ophthalmic genetics》2016,37(1):102-108
Background: Mutations in BEST1 account for autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare inherited retinal dystrophy with presenile cataracts and incomplete anterior segment development. The long-term clinical findings and visual prognosis of these patients continues to evolve over time.Materials and Methods: The retina was assessed by fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Sanger dideoxy chain-termination sequencing identified mutations in BEST1. Bioinformatic tools were used to predict changes in splicing. An in vitro splicing assay was applied to evaluate for altered pre-mRNA splicing.Results: Long-term follow up of the first ever reported ADVIRC proband revealed progressive foveal atrophy in both eyes 3 decades after his initial presentation. Progressive retinal ischemia, bilateral iris atrophy, and pseudophakodnesis were observed on follow up. The patient was heterozygous for a c.248G?>?A missense mutation in exon 4 of BEST1, affecting a highly conserved transmembrane domain. Although computational prediction models suggest a change in the binding probability of splicing-associated SR proteins, in vitro splicing assays failed to demonstrate an effect of the c.248G?>?A mutation on splicing of BEST1 exon 3 or exon 4.Conclusions: Progressive posterior chorioretinal changes occurred over time in the initial ADVIRC proband, leading to visual loss. The causative mutation in this patient falls in the transmembrane domain of the BEST1 protein, with unclear functional consequences. Although previous studies showed alteration in pre-mRNA splicing, in vitro splicing assays failed to demonstrate this in our patient. 相似文献
992.
《Biomaterials》2015
Mesoporous silica nanoparticles (MSNs) can provide a structural foundation for a new generation of nanocarriers with a broad range of functionalities. Multifunctional MSNs can serve as all-in-one diagnostic and therapeutic tools that can be used to simultaneously visualize and treat various diseases, such as cancer. This research study is the first time that two lanthanide-based imaging systems have been combined to incorporate controlled drug release and targeted tracing into a single MSN-based nano-platform for a novel theranostic drug delivery system. Doping lanthanide ions, i.e., europium (Eu) and gadolinium (Gd) ions, into an MSN structure (EuGd-MSNs) imparts fluorescence and magnetism to the nanostructure that can be used to develop magnetic resonance imaging (MRI) and biological fluorescence tools. Current cancer research has revealed that most human cancer cells express a large number of folate receptors on their surface. Grafting folic acid (FA) onto the EuGd-MSN surface (EuGd-FA-MSNs) imparts a targeting function to the MSN because of the specificity of the binding of FA to cell surface receptors. Furthermore, grafting anticancer drugs, such as camptothecin (CPT), onto the surface of these MSNs by forming disulfide bonds (EuGd-SS-CPT-FA-MSNs) enables intracellular controlled drug release. A high concentration of intracellular glutathione cleaves the disulfide bond to release the drug and treat the disease. The results of in vitro and in vivo studies show that the functionalized MSNs can be successfully used as a platform to integrate dual-imaging, targeting, and therapeutic treatment in multifunctional diagnosis drug delivery systems. 相似文献
993.
994.
Imaging chemical exchange saturation transfer (CEST) effects following tumor‐selective acidification using lonidamine 下载免费PDF全文
Increased lactate production through glycolysis in aerobic conditions is a hallmark of cancer. Some anticancer drugs have been designed to exploit elevated glycolysis in cancer cells. For example, lonidamine (LND) inhibits lactate transport, leading to intracellular acidification in cancer cells. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on intracellular pH. Amine and amide concentration‐independent detection (AACID) and apparent amide proton transfer (APT*) represent two recently developed CEST contrast parameters that are sensitive to pH. The goal of this study was to compare the sensitivity of AACID and APT* for the detection of tumor‐selective acidification after LND injection. Using a 9.4‐T MRI scanner, CEST data were acquired in mice approximately 14 days after the implantation of 105 U87 human glioblastoma multiforme (GBM) cells in the brain, before and after the administration of LND (dose, 50 or 100 mg/kg). Significant dose‐dependent LND‐induced changes in the measured CEST parameters were detected in brain regions spatially correlated with implanted tumors. Importantly, no changes were observed in T1‐ and T2‐weighted images acquired before and after LND treatment. The AACID and APT* contrast measured before and after LND injection exhibited similar pH sensitivity. Interestingly, LND‐induced contrast maps showed increased heterogeneity compared with pre‐injection CEST maps. These results demonstrate that CEST contrast changes after the administration of LND could help to localize brain cancer and monitor tumor response to chemotherapy within 1 h of treatment. The LND CEST experiment uses an anticancer drug to induce a metabolic change detectable by endogenous MRI contrast, and therefore represents a unique cancer detection paradigm which differs from other current molecular imaging techniques that require the injection of an imaging contrast agent or tracer. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
995.
Increased brain perfusion contrast with T2‐prepared intravoxel incoherent motion (T2prep IVIM) MRI 下载免费PDF全文
The feasibility to measure brain perfusion using intravoxel incoherent motion (IVIM) MRI has been reported recently with currently clinically available technology. The method is intrinsically local and quantitative, but is contaminated by partial volume effects with cerebrospinal fluid (CSF). Signal from CSF can be suppressed by a 180° inversion recovery (180°‐IR) magnetization preparation, but this also leads to strong suppression of blood and brain tissue signal. Here, we take advantage of the different T2 relaxations of blood and brain relative to CSF, and implement a T2‐prepared IVIM (T2prep IVIM) inversion recovery acquisition, which permits a recovery of between 43% and 57% of arterial and venous blood magnetization at excitation time compared with the theoretical recovery of between 27% and 30% with a standard 180°‐IR. We acquired standard IVIM (IVIM), T2prep IVIM and dynamic susceptibility contrast (DSC) images at 3 T using a 32‐multichannel receiver head coil in eight patients with known large high‐grade brain tumors. We compared the contrast and contrast‐to‐noise ratio obtained in the corresponding cerebral blood volume images quantitatively, as well as subjectively by two neuroradiologists. Our findings suggest that quantitative cerebral blood volume contrast and contrast‐to‐noise ratio, as well as subjective lesion detection, contrast quality and diagnostic confidence, are increased with T2prep IVIM relative to IVIM and DSC. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
996.
997.
目的探讨经皮冠状动脉介入(PCI)和静脉溶栓在急性心肌梗死患者中的应用价值。方法选择我院2013年1月至2014年9月收治的60例急性心肌梗死患者作为研究对象,随机分为实验组和对照组各30例。实验组患者采用PCI治疗,对照组患者采用静脉溶栓治疗,比较两组患者血管再通率、死亡发生率、ST段回落情况、住院时间、近远期不良事件发生率、左室舒张末径和左室射血分数变化情况。结果实验组血管再通率显著高于对照组,差异有统计学意义(P<0.05),而近期和远期不良事件发生率均低于对照组,近期不良事件发生率组间比较差异有统计学意义(P<0.05),而远期不良事件发生率比较差异无统计学意义(P>0.05)。实验组患者死亡发生率、ST段回落和住院时间均低于对照组,差异均有统计学意义(P<0.05)。实验组左室射血分数在术后1个月、3个月和6个月时均显著高于对照组,差异均有统计学意义(P<0.05)。结论急性心肌梗死患者应用PCI治疗可显著提高血管再通率、降低死亡和不良事件发生率,有效改善心功能。 相似文献
998.
目的:观察脑心通胶囊(步长制药)治疗脑梗死合并心肌缺血患者的临床疗效。方法选取2013年10月至2014年12月北京21所医院神经内科收治的符合入组条件的急性脑梗死伴心肌缺血患者,非随机分为脑心通组(基础治疗基础上加用步长脑心通胶囊)和对照组(仅基础治疗)。对比分析第4周、8周、12周时2组心电图变化以及使用NIHSS和改良mRankin评估第12周时神经功能变化。结果入组544例,剔除16例(不良事件2例、自动放弃1例、违背规则1例、失访6例、其他6例),实际完成试验528例(包含测量资料缺失病例),其中脑心通组291例,对照组237例。心肌缺血改善的有效率脑心通组和对照组第4周差异无统计学意义(18.1%、14.9%, P =0.704);但第8周(27.7%、14.3%, P =0.001)和第12周(31.3%、16.9%,P <0.01)差异有统计学意义( P <0.05)。第12周时NIHSS减少≥2分脑心通组(77.7%)明显高于对照组(68.4%)( P <0.05),mRankin 减少≥1分脑心通组(67.7%)显著高于对照组(56.1%)( P <0.05)。多因素分析心电图改善的独立影响因素是脑心通( P =0.005)和第12周时AST的降低( P =00.47);神经功能改善的影响因素包括脑心通治疗、基线收缩压和肌酐水平、既往心脏病或高脂血症病史。结论脑心通胶囊联合基础治疗对脑梗死合并心肌缺血临床疗效确切。 相似文献
999.
《Vaccine》2016,34(28):3310-3316
In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab′)2 fragments produced from Equine Rabies Immunoglobulin (F(ab′)2 – ERIGs). According to international regulation, quality control of F(ab′)2 – ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab′)2 – ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab′)2 – ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r = 0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice. 相似文献
1000.