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Phoenix, AZ, United States

Schraml F.V.,Barrow Neurologic Institute | Beason-Held L.L.,U.S. National Institute on Aging
Neuroendocrinology Letters | Year: 2010

OBJECTIVE: The purpose of this study was to correlate hypothyroid-related symptomatology with regional cerebral blood flow (rCBF) during hypothyroidism. MATERIALS AND METHODS: Nine thyroidectomized patients underwent neuropsychological testing and single photon emission computed tomography (SPECT) of their brains with technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), a lipophilic cerebral blood flow radiotracer, while hypothyroid, and again following thyroid hormone replacement. Neuropsychological test scores and TSH levels while hypothyroid were correlated with rCBF in hypothyroid-affected areas of the brain. RESULTS: Correlations were found during hypothyroidism between the noted parameters and ECD radiotracer accumulation in the following respective regions, all of which demonstrated hypothyroid-related cerebral blood flow (CBF) aberrations: TSH and left middle occipital gyrus; psychomotor performance speed and left precentral gyrus; and depression and right middle frontal gyrus, left middle frontal gyrus, right insula, and left thalamus. CONCLUSIONS: Severity of psychomotor impairment and depression, and TSH level during hypothyroidism appeared to correlate with CBF to brain regions associated with motor activity, mood and vision, respectively; and previously shown to manifest significantly altered rCBF during hypothyroidism. © 2010 Neuroendocrinology Letters.

Kidd S.A.,National Fragile X Foundation | Lachiewicz A.,Duke University | Barbouth D.,University of Miami | Blitz R.K.,Barrow Neurologic Institute | And 5 more authors.
Pediatrics | Year: 2014

Fragile X syndrome (FXS) is the most common known genetic cause of inherited intellectual disability and the most common known single-gene cause of autism spectrum disorder. It has been reported that a spectrum of medical problems are commonly experienced by people with FXS, such as otitis media, seizures, and gastrointestinal problems. Previous studies examining the prevalence of medical problems related to FXS have been challenging to interpret because of their marked differences in population, setting, and sampling. Through this comprehensive review, we update the literature by reviewing studies that have reported on prominent medical problems associated with FXS. We then compare prevalence results from those studies with results from a large cross-sectional database consisting of data collected by fragile X clinics that specialize in the care of children with FXS and are part of the Fragile X Clinical and Research Consortium. It is vital for pediatricians and other clinicians to be familiar with the medical problems related to FXS so that affected patients may receive proper diagnosis and treatment; improved care may lead to better quality of life for these patients and their families. Copyright © 2014 by the American Academy of Pediatrics.

Weltzin M.M.,Barrow Neurologic Institute | Schulte M.K.,University of the Sciences in Philadelphia
Journal of Pharmacology and Experimental Therapeutics | Year: 2015

Alterations in expression patterns of α4β2 nicotinic acetylcholine receptors have been demonstrated to alter cholinergic neurotransmission and are implicated in neurologic disorders, including autism, nicotine addiction, Alzheimer's disease, and Parkinson's disease. Positive allosteric modulators (PAMs) represent promising new leads in the development of therapeutic agents for the treatment of these disorders. This study investigates the involvement of the β2-containing subunit interfaces of α4β2 receptors in the modulation of acetylcholine (ACh)-induced responses by the PAM desformylflustrabromine (dFBr). Eight amino acids on the principal face of the β2 subunit were mutated to alanine to explore the involvement of this region in the potentiation of ACh-induced currents by dFBr. A Chinduced responses obtained from wild-type and mutant α4β2 receptors expressed in Xenopus laevis oocytes were recorded in the presence and absence of dFBr using two-electrode voltage clamp electrophysiology. Wild-type and mutant receptors were expressed in both high and low ACh sensitivity isoforms by using biased injection ratios of 1:5 or 5:1 α4 to β2 complementary RNA. Mutations were made in the B, C, and A loops of the principal face of the β2 subunit, which are regions not involved in the binding of ACh. Mutant β2(Y120A) significantly eliminated dFBr potency in both isoform preparations. Several other mutations altered dFBr potentiation levels in both preparations. Our findings support the involvement of the principal face of the β2 subunit in dFBr modulation of ACh-induced responses. Findings from this study will aid in the improved design of dF Brlike PAMs for potential therapeutic use. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Willson M.C.,Foothills Medical Center | Ross J.S.,Barrow Neurologic Institute
Neuroimaging Clinics of North America | Year: 2014

Imaging of the postoperative spine is common, although it remains a difficult task for radiologists. This article presents an overview of common surgical approaches and spinal hardware, and specific complications that may be associated with each procedure. In addition, expected postoperative changes and complications that are common among procedures, with their differential diagnosis and imaging features, are discussed. © 2014 Elsevier Inc.

Moretti M.,CNR Institute of Neuroscience | Zoli M.,University of Modena and Reggio Emilia | George A.A.,Barrow Neurologic Institute | Lukas R.J.,Barrow Neurologic Institute | And 4 more authors.
Molecular Pharmacology | Year: 2014

We examined α7β2-nicotinic acetylcholine receptor (α7β2-nAChR) expression in mammalian brain and compared pharmacological profiles of homomeric α7- nAChRs and α7β2-nAChRs. α-Bungarotoxin affinity purification or immunoprecipitation with anti-α7 subunit antibodies (Abs) was used to isolate nAChRs containing α7 subunits from mouse or human brain samples. α7β2-nAChRs were detected in forebrain, but not other tested regions, from both species, based on Western blot analysis of isolates using β2 subunit-specific Abs. Ab specificity was confirmed in control studies using subunit-null mutant mice or cell lines heterologously expressing specific human nAChR subtypes and subunits. Functional expression in Xenopus oocytes of concatenated pentameric (α7) 5-, (α7)4(β2) 1-, and (α7)3(β2) 2-nAChRs was confirmed using two-electrode voltage clamp recording of responses to nicotinic ligands. Importantly, pharmacological profiles were indistinguishable for concatenated (α7)5-nAChRs or for homomeric α7-nAChRs constituted from unlinked α7 subunits. Pharmacological profiles were similar for (α7)5-, (α7)4(β 2)1-, and (α7) 3(β2)2-nAChRs except for diminished efficacy of nicotine (normalized to acetylcholine efficacy) at α7β2- versus α7-nAChRs. This study represents the first direct confirmation of α7β 2-nAChR expression in human and mouse forebrain, supporting previous mouse studies that suggested relevance of α7β2- nAChRs in Alzheimer disease etiopathogenesis. These data also indicate that α7β2-nAChR subunit isoforms with different α7/β2 subunit ratios have similar pharmacological profiles to each other and to α7 homopentameric nAChRs. This supports the hypothesis that α7β 2-nAChR agonist activation predominantly or entirely reflects binding to α7/α7 subunit interface sites. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

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