The three human alleles of apolipoprotein E (APOE) differentially influence outcome after CNS injury and affect one's risk of developing Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g., amyloid plaques and synaptic and neuron loss). Here, we systematically examined whether apoE isoforms (E2, E3, E4) exhibit differential effects on dendritic spine density and morphology in APOE targeted replacement (TR) mice, which lack AD pathological changes. Using Golgi staining, we found age-dependent effects of APOE4 on spine density in the cortex. The APOE4 TR mice had significantly reduced spine density at three independent time points (4 weeks, 3 months, and 1 year, 27.7% Ϯ 7.4%, 24.4% Ϯ 8.6%, and 55.6% Ϯ 10.5%, respectively) compared with APOE3 TR mice and APOE2 TR mice. Additionally, in APOE4 TR mice, shorter spines were evident compared with other APOE TR mice at 1 year. APOE2 TR mice exhibited longer spines as well as significantly increased apical dendritic arborization in the cortex compared with APOE4 and APOE3 TR mice at 4 weeks. However, there were no differences in spine density across APOE genotypes in hippocampus. These findings demonstrate that apoE isoforms differentially affect dendritic complexity and spine formation, suggesting a role for APOE genotypes not only in acute and chronic brain injuries including AD, but also in normal brain functions.
BackgroundApolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ clearance. We previously showed that an apoE-derived peptide containing a double repeat of the receptor-binding region was similarly effective in increasing APP processing in vivo. Here, we further examined whether peptides containing tandem repeats of the apoE receptor-binding region (amino acids 141-149) affected APP trafficking, APP processing, and Aβ production.ResultsWe found that peptides containing a double or triple tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased cell surface APP and decreased Aβ levels in PS1-overexpressing PS70 cells and in primary neurons. This effect was potentiated by a sequential increase in the number of apoE receptor-binding domain repeats (trimer > dimer > monomer). We previously showed that the apoE dimer increased APP CTF in vivo; to determine whether the dimer also affected secreted APP or Aβ levels, we performed a single hippocampal injection of the apoE dimer in wild-type mice and analyzed its effect on APP processing. We found increased sAPPα and decreased Aβ levels at 24 hrs after treatment, suggesting that the apoE dimer may increase α-secretase cleavage.ConclusionsThese data suggest that small peptides consisting of tandem repeats of the apoE receptor-binding region are sufficient to alter APP trafficking and processing. The potency of these peptides increased with increasing repeats of the receptor binding domain of apoE. In addition, in vivo administration of the apoE peptide (dimer) increased sAPPα and decreased Aβ levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Aβ production both in vitro and in vivo.
The aim of this study was to determine the prevalence of different diagnostic image viewing platforms used by radiologists while on-call, and to assess the opinions and preferences of radiology program directors and chief residents regarding their use. An online survey was sent electronically to radiology residency program directors and chief residents via the Association of University Radiologists. Forty-two radiology program directors and 25 chief residents completed the survey, yielding response rates of 24.9 and 8.5 %, respectively. From the survey results, 10 different Picture Archiving Communications Systems (PACS) were identified; GE (25 %), Philips (17 %), and Agfa Impax (15 %) were the most prevalent. Interestingly, only 5 % of all respondents use a secondary "Digital Imaging and Communications in Medicine" viewer for oncall studies. Perceptions of PACS functionality were generally neutral to weakly positive. Most respondents strongly agreed that it is important to have a single integrated PACS for viewing oncall studies and agreed that the PACS should be integrated into the Electronic Medical Records (EMR). The overwhelming majority of respondents use their institution's PACS while oncall. The results show there is still a wide variety of PACS platforms used by different institutions; however, GE, Phillips, and Agfa were some of the most prevalent. Most radiologists surveyed have neutral to slightly positive perceptions about the functionality and ease of use of their PACS. Finally, while radiologists agree that PACS should be integrated with EMR, only 53 % of respondents currently have this arrangement.
Purpose:(1) To assess the efficacy of empiric gastroduodenal artery and left gastric artery embolization in reducing recurrent hemorrhage compared to image-guided targeted embolization.(2) To assess the efficacy of embolization of the GDA in reducing recurrent hemorrhage compared to the LGA. Materials and Methods:A single-institution retrospective study was done by reviewing medical records of patients who had catheter angiography for major upper gastrointestinal bleeding (UGIB) refractory to endoscopic intervention from June 2009 to April 2013 (n ¼ 53). Groups were assigned based on either targeted or empiric embolization. Technical success was defined as absence of contrast extravasation by the vessel of interest and collateral circulation. Clinical success was defined as a combination of technical success with an improvement in hemoglobin, no evidence of further hemorrhage after embolization, and no requirement for further intervention in the successive four weeks.Results: The technical and clinical success rates for targeted and empiric embolization groups were, respectively, 100 vs. 100%, and 88 vs. 93%. There was no statistical significance in the recurrent hemorrhage rate, reintervention rate, or 30 day mortality between targeted and empiric embolization groups.The technical and clinical success rates for embolization of the GDA and LGA were, respectively, 100 vs. 100%, and 81 vs. 94%. There was no statistical significance in the recurrent hemorrhage rate, reintervention rate, or 30 day mortality between GDA and LGA embolization. Conclusion:In patients with upper gastrointestinal bleeding refractory to endoscopic interventions, empiric embolization should be considered as the first-line management to control the hemorrhage. Empiric embolization of the GDA or LGA in patients with major UGIB refractory to endoscopic treatment appears to be a safe and effective treatment, with low reintervention rates and good clinical outcomes that are comparable to that of patients where the site of hemorrhage is localized and embolized under the guidance of imaging. Embolization of the GDA and LGA also demonstrate similar outcomes with regards to low rebleeding rates, low reintervention rates, and good clinical outcomes.
In 1964, Charles Dotter and Melvin Judkins performed the first successful transluminal angioplasty of a superficial femoral artery stenosis. Since then, techniques of revascularization have been the cornerstone of interventional radiology (IR) practices. Angioplasty became a more recognized therapy in the mid-1970s, and in the ensuing 40 years, there have been continual advancements in this technology, resulting in highly sophisticated devices that are now available in IR suites around the world. The array of materials available is constantly evolving, as are the various uses of balloons and stents. In addition to their use in restoring patency of occluded or stenotic arteries and veins, balloons and stents are employed to restore patency in other structures, including bile ducts and ureters. In this chapter, properties of these commonly used tools and indications for their use are discussed in detail.
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