Medicine and Health Sciences Commons^™

Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis, Rebecca A. Drummond, Jigar V. Desai, Amy P. Hsu, Vasileios Oikonomou, Donald C. Vinh, Joshua A. Acklin, Michael S. Abers, Magdalena A. Walkiewicz, Sarah L. Anzick, Muthulekha Swamydas, Simon Vautier, Mukil Natarajan, Andrew J. Oler, Daisuke Yamanaka, Katrin D. Mayer-Barber, Yoichiro Iwakura, David Bianchi, Brian Driscoll, Ken Hauck, Ahnika Kline, Nicholas S.P. Viall, Christa S. Zerbe, Elise M.N. Ferré, Monica M. Schmitt, Tom Dimaggio, Stefania Pittaluga, John A. Butman, Adrian M. Zelazny, Yvonne R. Shea, Cesar A. Arias, Cameron Ashbaugh, Maryam Mahmood, Zelalem Temesgen, Alexander G. Theofiles, Masayuki Nigo, Varsha Moudgal, Karen C. Bloch, Sean G. Kelly, M. Suzanne Whitworth, Ganesh Rao, Cindy J. Whitener, Neema Mafi, Juan Gea-Banacloche, Lawrence C. Kenyon, William R. Miller, Katia Boggian, Andrea Gilbert, Matthew Sincock, Alexandra F. Freeman, John E. Bennett, Rodrigo Hasbun, Constantinos M. Mikelis, Kyung J. Kwon-Chung, Yasmine Belkaid, Gordon D. Brown, Jean K. Lim, Douglas B. Kuhns, Steven M. Holland, Michail S. Lionakis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, β-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1β in response to β-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1β and …

68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …

Association Of Metabolic Syndrome And Change In Unified Parkinson's Disease Rating Scale Scores., Maureen Leehey, Sheng Luo, Saloni Sharma, Anne-Marie A. Wills, Jacquelyn L. Bainbridge, Pei Shieen Wong, David K. Simon, Jay S Schneider, Yunxi Zhang, Adriana Pérez, Rohit Dhall, Chadwick W. Christine, Carlos Singer, Franca Cambi, James T Boyd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).

METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits …

Strain Specific Effects Of Low Level Lead Exposure On Associative Learning And Memory In Rats., Megha Verma, J. S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Exposure to lead (Pb) remains a significant public health concern. Lead exposure in early life impairs the normal development of numerous cognitive and neurobehavioral processes. Previous work has shown that the effects of developmental Pb exposure on gene expression patterns in the brain are modulated by various factors including the developmental timing of the exposure, level of exposure, sex, and genetic background. Using gene microarray profiling, we previously reported a significant strain-specific effect of Pb exposure on the hippocampal transcriptome, with the greatest number of differentially expressed transcripts in Long Evans (LE) rats and the fewest in Sprague Dawley (SD) …

Caffeine And Progression Of Parkinson Disease: A Deleterious Interaction With Creatine., David K. Simon, Cai Wu, Barbara C. Tilley, Anne-Marie Wills, Michael J. Aminoff, Jacquelyn Bainbridge, Robert A. Hauser, Jay S. Schneider, Saloni Sharma, Carlos Singer, Caroline M. Tanner, Daniel Truong, Pei Shieen Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake.

METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from …

Compensatory Fetal Membrane Mechanisms Between Biglycan And Decorin In Inflammation., Luciana Batalha De Miranda De Araujo, Casie E Horgan, Abraham Aron, Renato V. Iozzo, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, …

The Variable Presentations Of Anaplastic Spindle Cell Squamous Carcinoma Associated With Tall Cell Variant Of Papillary Thyroid Carcinoma., Pallavi P Gopal, Kathleen T Montone, Zubair Baloch, Madalina Tuluc, Virginia Livolsi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In 1976, Hawk and Hazard described the tall cell variant (TCV) of papillary thyroid carcinoma (PTC). While the lesions they described had cytologic features of papillary carcinoma, they showed more aggressive behavior with a greater propensity for extrathyroid extension and lymphovascular invasion than classic PTC. In 1991, Bronner and LiVolsi described a series of patients with TCV that progressed to spindle cell squamous carcinoma (SCSC), a unique form of anaplastic thyroid carcinoma. This study describes the variable clinical and pathologic presentations in 31 patients with anaplastic SCSC arising in association with TCV.

METHODS: The surgical pathology archives as well …

Multiple Forms Of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15., Nicholas J Wang, Alexander S Parokonny, Karen N Thatcher, Jennette Driscoll, Barbara M Malone, Naghmeh Dorrani, Marian Sigman, Janine M Lasalle, N Carolyn Schanen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15)] that has been called inverted duplication 15 or isodicentric 15 [idic(15)], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR) that are found clustered in the …

Palm Is Expressed In Both Developing And Adult Mouse Lens And Retina., Meryl Castellini, Louise V Wolf, Bharesh K Chauhan, Deni S Galileo, Manfred W Kilimann, Ales Cvekl, Melinda K Duncan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real time rt-PCR. RESULTS: In the …