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Elaine Delvaux Karen Bentley Victoria Stubbs Marwan Sabbagh Paul D. Coleman 《Neurobiology of aging》2013
Because amyloid precursor protein (APP) fragments exist in many tissues throughout the body, including the fluid compartments of blood, they have been the focus of numerous investigations into their potential as a biomarker of Alzheimer's disease. Using immunohistochemistry, immunoelectron microscopy, Western blot, and quantitative real-time-polymerase chain reaction (qRT-PCR) analysis we examined whether APP processing in leukocytes is analogous to APP processing in the brain. We show APP immunoreactivity at light and electron microscopic levels in the cytoplasm and nucleus of peripheral blood leukocytes (PBL) yet our Western blot analysis data demonstrated that brain and PBL contain different APP fragments and differentially expressed APP processing enzymes. A Disintegrin and Metalloproteinase domain 10 (ADAM10), nicastrin, and beta-secretase 2 (BACE2) were present in brain but were undetected in PBL. Presenilin 1 and beta-secretase 1 (BACE1) were detected in both tissues but showed different patterns in Western blots. Quantitative PCR results identified Neprilysin as the only processing enzyme we interrogated in which Western and quantitative PCR data coincided. Although our data on differential processing of APP in brain and PBL point to exercising caution when generalizing between blood and brain with regard to mechanisms, they have no implications regarding utility as biomarkers. 相似文献
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Todd C. Villines Subhi J. Al’Aref Daniele Andreini Marcus Y. Chen Andrew D. Choi Carlo N. De Cecco Damini Dey James P. Earls Maros Ferencik Heidi Gransar Harvey Hecht Jonathon A. Leipsic Michael T. Lu Mohamed Marwan Pál Maurovich-Horvat Edward Nicol Gianluca Pontone Jonathan Weir-McCall Gudrun M. Feuchtner 《Journal of Cardiovascular Computed Tomography》2021,15(2):180-189
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Health literacy in patients referred for transplant: do patients have the capacity to understand? 下载免费PDF全文
Lisa R. Miller‐Matero Maren E. Hyde‐Nolan Anne Eshelman Marwan Abouljoud 《Clinical transplantation》2015,29(4):336-342
Adequate levels of health literacy are needed for transplant recipients to be able to understand and comply with medical recommendations. However, little is known about health literacy among transplant candidates. Therefore, the purpose of this study was to examine the levels of health literacy and cognitive functioning among patients being evaluated for various types of transplantation. There were 398 patients who completed a required psychological evaluation prior to being listed for transplant. This included a screen for cognitive impairment and limited reading and math ability. The prevalence of limited reading ability was 27.5%, limited math ability was 42.8%, and 30.7% had probable cognitive impairment. Rates of limited reading and math ability and cognitive impairment varied for each type of end‐stage disease. Limited reading ability was related to poorer cognitive functioning. Those with a higher likelihood of limited reading ability included blacks and males. Those more likely to have cognitive impairment included blacks and patients who are older. Results from this study suggest that patients should be regularly screened for health literacy and cognitive impairment. Once patients with difficulties are identified, recommendations can be provided to these patients at a level that they are able to understand. 相似文献
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Celestino-Soper PB Violante S Crawford EL Luo R Lionel AC Delaby E Cai G Sadikovic B Lee K Lo C Gao K Person RE Moss TJ German JR Huang N Shinawi M Treadwell-Deering D Szatmari P Roberts W Fernandez B Schroer RJ Stevenson RE Buxbaum JD Betancur C Scherer SW Sanders SJ Geschwind DH Sutcliffe JS Hurles ME Wanders RJ Shaw CA Leal SM Cook EH Goin-Kochel RP Vaz FM Beaudet AL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):7974-7981
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism. 相似文献
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Rickard L. Sjöberg Björn Häggström Johanna Philipsson Jan Linder Marwan Hariz Patric Blomstedt 《Neurocase》2013,19(5):601-606
Ear advantage during a dichotic listening task tends to mirror speech lateralization. Previous studies in stroke patients have shown that lesions in the dominant hemisphere often seem to produce changes in ear advantage. In this study six Parkinson’s disease (PD) patients treated for motor symptoms with deep brain stimulation (DBS) of the left subthalamic nucleus (STN) were tested preoperatively and at approximately 6 and 18 months postoperatively with a dichotic listening task. Results show a significant decline of the right ear advantage over time. In three of the patients a right ear advantage preoperativley changed to a left ear advantage 18 months postoperatively. This suggests the possibility that additional longitudinal studies of this phenomenon could serve as a model for understanding changes in indirect measures of speech lateralization in stroke patients. 相似文献
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Laura Cif Diane Ruge Victoria Gonzalez Patricia Limousin Xavier Vasques Marwan I. Hariz John Rothwell Philippe Coubes 《Brain stimulation》2013,6(4):500-505
BackgroundDeep brain stimulation (DBS) of the internal globus pallidus (GPi) is an established therapy for primary generalized dystonia. However, the evolution of dystonia symptoms after DBS discontinuation after years of therapy has only rarely been reported. We therefore longitudinally studied the main physiological measurements known to be impaired in dystonia, with DBS ON and then again after termination of DBS, after at least five years of continuous DBS.ObjectiveWe studied whether dystonia evolution after DBS discontinuation in patients benefiting from long-term GPi DBS is different from that observed in earlier stages of the therapy.MethodsIn eleven DYT1 patients treated with bilateral GPi DBS for at least 5 years, dystonia was assessed ON-DBS, immediately after switch-off (OFF-DBS1) and 48 h after DBS termination (OFF-DBS2). We studied the influence of DBS intensity on dystonia when DBS was discontinued.ResultsOn average a significant difference in symptoms was measured only between ON-DBS and OFF-DBS1 conditions. Importantly, none of the patients returned to their preoperative dystonia severity, even 48 h after discontinuation. The amount of clinical deterioration in the OFF conditions positively correlated with higher stimulation current in the chronic ON-DBS condition.ConclusionsThe duration of DBS application influences symptom evolution after DBS termination. DBS intensity seems to have a prominent role on evolution of dystonic symptoms when DBS is discontinued. In conclusion, DBS induces changing modulation of the motor network with less worsening of symptoms after long term stimulation, when DBS is stopped. 相似文献
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