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Smith, Edward R. The Korean Neurosurgical Society 2015 Journal of Korean neurosurgical society Vol.57 No.6
Moyamoya disease (MMD) is an arteriopathy of the intracranial circulation predominantly affecting the branches of the internal carotid arteries. Heterogeneity in presentation, progression and response to therapy has prompted intense study to improve the diagnosis and prognosis of this disease. Recent progress in the development of moyamoya-related biomarkers has stimulated marked interest in this field. Biomarkers can be defined as biologically derived agents-such as specific molecules or unique patterns on imaging-that can identify the presence of disease or help to predict its course. This article reviews the current categories of biomarkers relevant to MMD-including proteins, cells and genes-along with potential limitations and applications for their use.
Pediatric Cerebral Vascular Malformations : Current and Future Perspectives
Edward R. Smith 대한신경외과학회 2024 Journal of Korean neurosurgical society Vol.67 No.3
Intracranial vascular malformations typically encountered by pediatric neurosurgeons include arteriovenous malformations, vein of Galen malformations and cavernous malformations. While these remain amongst some of the most challenging lesions faced by patients and caregivers, the past decade has produced marked advances in the understanding of the pathophysiology of these conditions, with concomitant innovations in treatment. This article will highlight present and future perspectives relevant to these diseases, with a focus on an emerging approach utilizing disease-specific mutations to develop a novel taxonomy for these conditions.
Edwards, H.D.,Shelver, W.L.,Choi, S.,Nisbet, D.J.,Krueger, N.A.,Anderson, R.C.,Smith, S.B. Applied Science Publishers 2017 Food chemistry Vol.218 No.-
Lipolysis and biohydrogenation in ruminal animals promote the accumulation of saturated fatty acids in their meat and milk. Antibodies were generated against key ruminal lipase contributors Anaerovibrio lipolyticus, Butyrivibrio fibrisolvens, Propionibacterium avidum and acnes. An anti-Pseudomonas lipase antibody was generated to determine if an antibody against a purified protein would be more effective. Each bacterium was cultured and assayed without or with increasing levels of each antibody. Butyrivibrio fibrisolvens H17C also participates in biohydrogenation and therefore the antibody was tested to determine if it could effectively reduce biohydrogenation. Butyrivibrio fibrisolvens was assayed without and with the anti-B. fibrisolvens antibody and linoleic or α-linolenic acid. All antibodies were effective at reducing lipolysis with the anti-Pseudomonas lipase averaging a 78% reduction. The anti-B. fibrisolvens showed a tendency for a reduction (P=0.0713) in biohydrogenation products of α-linolenic acid. Results demonstrate that lipolysis and biohydrogenation can be immunologically inhibited in vitro.
Management of Pediatric Intracranial Arteriovenous Malformations
Alfred Pokmeng See,Edward R. Smith 대한신경외과학회 2024 Journal of Korean neurosurgical society Vol.67 No.3
Pediatric intracranial arteriovenous malformations (AVMs) are challenging lesions managed by pediatric neurosurgeons. The high risk of hemorrhage and neurologic injury is compounded by the unique anatomy of each malformation that requires individualizing treatment options. This article reviews the current status of pediatric AVM epidemiology, pathophysiology and clinical care, with a specific focus on the rationale and methodology of surgical resection.
Katie Pricola Fehnel,David L. Penn,Micah Duggins-Warf,Maxwell Gruber,Steven Pineda,Julie Sesen,Alexander Moses-Gardner,Nishali Shah,Jessica Driscoll,David Zurakowski,Darren B. Orbach,Edward R. Smith 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2: EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n=30), other cerebrovascular disease (n=14) and control patients (n=29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p=0.04) and migration (p=0.08), impaired tube formation (p=0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p=0.03 and p<0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2>25.7pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Posttreatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.