Medical Specialties Commons^™

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.

RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …

The Production Of Antibody By Invading B Cells Is Required For The Clearance Of Rabies Virus From The Central Nervous System., D Craig Hooper, Timothy W Phares, Marzena J Fabis, Anirban Roy

Department of Cancer Biology Faculty Papers

BACKGROUND: The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.

METHODOLOGY/PRINCIPAL FINDINGS: Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies …

Intravenous Inoculation Of A Bat-Associated Rabies Virus Causes Lethal Encephalopathy In Mice Through Invasion Of The Brain Via Neurosecretory Hypothalamic Fibers., Mirjam A R Preuss, Marie-Luise Faber, Gene S Tan, Michael Bette, Bernhard Dietzschold, Eberhard Weihe, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

The majority of rabies virus (RV) infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS) where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown …

Y27632, A Rho-Activated Kinase Inhibitor, Normalizes Dysregulation In Alpha1-Adrenergic Receptor-Induced Contraction Of Lyon Hypertensive Rat Artery Smooth Muscle., Maria Regina Freitas, Masumi Eto, Jason A Kirkbride, Christa Schott, Jean Sassard, Jean-Claude Stoclet

Department of Molecular Physiology and Biophysics Faculty Papers

RhoA-activated kinase (ROK) is involved in the disorders of smooth muscle contraction found in hypertension model animals and patients. We examined whether the alpha1-adrenergic receptor agonist-induced ROK signal is perturbed in resistance small mesentery artery (SMA) of Lyon genetically hypertensive (LH) rats, using a ROK antagonist, Y27632. Smooth muscle strips of SMA and aorta were isolated from LH and Lyon normotensive (LN) rats. After Ca(2+)-depletion and pre-treatment with phenylephrine (PE), smooth muscle contraction was induced by serial additions of CaCl(2). In LH SMA Ca(2+) permeated cells to a lesser extent as compared with LN SMA, while CaCl(2)-induced contraction of LH …

The Efficacy Of Surgical Decompression Before 24 Hours Versus 24 To 72 Hours In Patients With Spinal Cord Injury From T1 To L1--With Specific Consideration On Ethics: A Randomized Controlled Trial., Vafa Rahimi-Movaghar, Soheil Saadat, Alexander R Vaccaro, Seyed Mohammad Ghodsi, Mohammad Samadian, Arya Sheykhmozaffari, Seyed Mohammad Safdari, Bahram Keshmirian

Department of Neurosurgery Faculty Papers

BACKGROUND: There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24-72 hours) surgical decompression in terms of neurological …

Autistic Disorder Associated With A Paternally Derived Unbalanced Translocation Leading To Duplication Of Chromosome 15pter-Q13.2: A Case Report., David J Wu, Nicholas J Wang, Jennette Driscoll, Naghmeh Dorrani, Dahai Liu, Marian Sigman, N Carolyn Schanen

Department of Pediatrics Faculty Papers

Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication …

Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta

Kimmel Cancer Center Faculty Papers

BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …