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 …

Solution Structure Of The Inhibitory Phosphorylation Domain Of Myosin Phosphatase Targeting Subunit 1., Shunsuke Mori, Ryou Iwaoka, Masumi Eto, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Cell motility, such as smooth muscle contraction and cell migration, is controlled by the reversible phosphorylation of the regulatory light chain of myosin II and other cytoskeletal proteins. Mounting evidence suggests that in smooth muscle cells and other types of cells in vertebrates, myosin phosphatase (MP) plays an important role in controlling the phosphorylation of myosin II as well as other cytoskeletal proteins, including ezrin, moesin, and radixin.1 MP is a holoenzyme consisting of a catalytic subunit of a type-1 Ser/Thr phosphatase (PP1C) delta isoform, a myosin phosphatase targeting subunit 1 (MYPT1), and an accessory subunit M21. In this ternary …

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 …

Sonography Of The Neonatal Brain, Traci B. Fox

Department of Radiologic Sciences Faculty Papers

Neurosonography is a critical part of the care of the sick newborn. Sonography is superior to other modalities in imaging of the brain because it can be performed at the bedside, is easily reproducible, and does not require ionizing radiation or sedation. This article refreshes the sonographer in the normal anatomy and appear- ance of the neonatal brain using sonography, as well as some of the more common pathologic conditions that may be encountered.

Embolic Complication Of Tako-Tsubo Cardiomyopathy., Vincent M. Figueredo, S Gupta

Department of Medical Genetics Faculty Papers

No abstract provided.

Imrt Commissioning: Multiple Institution Planning And Dosimetry Comparisons, A Report From Aapm Task Group 119., Gary A Ezzell, Jay W Burmeister, Nesrin Dogan, Thomas J Losasso, James G Mechalakos, Dimitris Mihailidis, Andrea Molineu, Jatinder R Palta, Chester R Ramsey, Bill J Salter, Jie Shi, Ping Xia, Ning J Yue, Ying Xiao, Phd

Department of Radiation Oncology Faculty Papers

AAPM Task Group 119 has produced quantitative confidence limits as baseline expectation values for IMRT commissioning. A set of test cases was developed to assess the overall accuracy of planning and delivery of IMRT treatments. Each test uses contours of targets and avoidance structures drawn within rectangular phantoms. These tests were planned, delivered, measured, and analyzed by nine facilities using a variety of IMRT planning and delivery systems. Each facility had passed the Radiological Physics Center credentialing tests for IMRT. The agreement between the planned and measured doses was determined using ion chamber dosimetry in high and low dose regions, …

Combination Of Vandetanib, Radiotherapy, And Irinotecan In The Lovo Human Colorectal Cancer Xenograft Model., Phyllis Wachsberger, Randy Burd, Anderson Ryan, Constantine Daskalakis, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

PURPOSE: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. METHODS AND MATERIALS: LoVo cells were injected subcutaneously into the right hind limb (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(3) before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3 x 3 Gy) …

Traumatic Thoracic Asia A Examinations And Potential For Clinical Trials, James S. Harrop, Md, Mitchell G. Maltenfort, Phd, Fred H. Geisler, Md, Phd, William Coleman, Phd, Linda A.T. Jones, Pt, Ms, Edward Wirth, Md, Alexander Vaccaro, Md, Phd

Department of Neurosurgery Faculty Papers

Study Design: Retrospective review of prospective database

Objectives: To define the variability of neurologic examination and recovery after non-penetrating complete thoracic spinal cord injuries (ASIA A).

Background Data: Neurologic examinations after SCI can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A – based on the ASIA Impairment Scale [AIS]) patients’ exams are based only on sensory testing, thus changes in the neurological level (NL) are determined only by sensory changes.

Methods: A retrospective review of the placebo control patients in a multicenter prospective database utilized for the pharmacologic trial of Sygen. …

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Overview-Charles J Yeo, Md

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Bariatric And Metabolic Surgery Program Turns A Life Around

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The Surgeon Speaks

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Download The Full Pdf Of Jefferson Surgical Solutions Fall 2009, Volume 4, Number 2.

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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 …

Spontaneous Left Main Coronary Artery Dissection, Possibly Due To Cystic Medial Necrosis Found In The Internal Mammary Arteries., Hitoshi Hirose, Iwao Matsunaga, Waqas Anjun, Michael D Strong

Department of Surgery Faculty Papers

A 55-year-old male without previous medical history developed chest pain. Coronary catheterization showed left main coronary dissection. Coronary artery bypass grafting was performed using bilateral internal mammary arteries, which were very fragile. The specimens of the internal mammary arteries sent for pathology showed cystic medial necrosis.

Somnoforme: A Century After The Introduction Of The "Ideal" Anesthetic Gas, James W. Heitz, Md

Department of Anesthesiology Faculty Papers

Since the introduction of ether as a general anesthetic, there has been a continuous quest to develop the ideal anesthetic gas. The attributes of the ideal anesthetic gas have evolved over time. At the beginning of the 20th century, the search for the ideal anesthetic was focused upon finding an anesthetic gas with rapid inhalation induction and rapid emergence that could be delivered without cumbersome apparatus and would have limited potential for toxicity. Somnoforme was a mixture of ethyl chloride, methyl chloride, and ethyl bromide designed to provide powerful efficacy with low potential for side effects by blending of several …

Sour Ageusia In Two Individuals Implicates Ion Channels Of The Asic And Pkd Families In Human Sour Taste Perception At The Anterior Tongue., Taufiqul Huque, Beverly J Cowart, Luba Dankulich-Nagrudny, Edmund A Pribitkin, Douglas L Bayley, Andrew I Spielman, Roy S Feldman, Scott A Mackler, Joseph G Brand

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli.

METHODS AND FINDINGS: Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1beta, 2a, …

Euroscore Predicts Postoperative Mortality, Certain Morbidities, And Recovery Time., Hitoshi Hirose, Hirotaka Inaba, Chiaki Noguchi, Keiichi Tambara, Taira Yamamoto, Motoshige Yamasaki, Keita Kikuchi, Atsushi Amano

Department of Surgery Faculty Papers

EuroSCORE (European System for Cardiac Operative Risk Evaluation) used for calculating the risk of the postoperative mortality rate for patients undergoing open-heart surgery may be able to predict postoperative complications as well. Consecutive cases of isolated on-pump coronary artery bypass grafting (CABG) (n=1552) performed between 1991 and 2006 at our hospital group were placed into a systematic database. Patients were stratified using additive EuroSCORE. Incidence of postoperative mortality, morbidity (bleeding, heart failure, mediastinitis, pneumonia, myocardial infarction, renal failure, and stroke), and recovery time (intubation time, ICU stay, and postoperative length of stay) was assessed in each EuroSCORE group. EuroSCORE was …

Oculocardiac Reflex Elicited During Debridement Of An Empty Orbit, James C. Tsai, Md, James W. Heitz, Md, Edward H. Bedrossian Jr, Md Facs

Wills Eye Hospital Papers

87 yo male with history of hypertension and right periorbital basal cell carcinoma s/p previous right total ethmoidectomy, right maxillary antrostomy, and complete right orbital exenteration for basal cell carcinoma invading the right ethmoid sinus. Functional endoscopic sinus surgery and orbital exploration was scheduled for excision of recurrent basal cell carcinoma. Rapid sequence induction and intubation was uneventful. During right orbital base curettage, the patient experienced several precipitious episodes of profound bradycardia or brief asystole. After surgery, the patient denied cardiac symptoms, and cardiac enzymes were all normal. Oculocardiac-mediated bradyarrhythmias are rarely elicited from empty orbits.

Foxp3-Expressing T Regulatory Cells (T-Regs) Increase With The Severity Of Active Disease In Chronic Hepatitis C, Adam D. Toll, Md, John L. Farber, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The hepatitis C virus (HCV) leads to chronic disease in 80% of those infected and is associated with a chronic inflammatory response that is mediated by both cytokine producing (CD4+) and cytotoxic T cells (CD8+). FoxP3-expressing, CD4+, CD25+T cells (T-regs) are a subset of T lymphocytes that inhibit immune responsiveness and thereby control immunological reactions. Whether FoxP3+ T regulatory cell-mediated suppression is a factor in HCV persistence and/or the course of chronic liver injury has not been defined. In order to assess the association between these T regulatory cells and the severity of chronic hepatitis C, we evaluated liver biopsies …

The Otto Aufranc Award Identification Of A 4 Mb Region On Chromosome 17q21 Linked To Developmental Dysplasia Of The Hip In One 18-Member, Multigeneration Family, George Feldman, Chelsea Dalsey, Kasia Fertala, David Azimi, Paolo Fortina, Marcella Devoto, Maurizio Pacifici, Javad Parvizi

Department of Orthopaedic Surgery Faculty Papers

Developmental dysplasia of the hip (DDH) is a disabling condition of the hip that, depending on geography, can afflict between 20-80% of patients with end-stage arthritis of the hip. Despite its prevalence, the etiology of this disease remains unknown. DDH is a complex disorder with both environmental and genetic causes.. Based on the literature, the candidate genes for the disease are HOXB9, collagen type I α1, and DLX 3. The purpose of our study was to map and characterize the gene or genes responsible for this disorder by family linkage analysis. We recruited one 18-member, multigeneration affected family to provide …

Utilization Of Dantrolene In Stiff-Person Syndrome: A Case Report, John M. Vasudevan, Md, S. Kamal Fetouh, Md,, Nethra S. Ankam, Md, Adam L. Schreiber, Do, Ma

Department of Rehabilitation Medicine Faculty Papers

Setting: University hospital-based acute rehabilitation.

Patient: 75-year-old woman with Stiff-Person Syndrome (SPS) with a recent fall and Colles fracture.

Case Description: Four months prior to admission, the patient was diagnosed with SPS, negative for anti-GAD antibodies. Diagnosis was based on a 3-year history of progressive rigidity leading to frequent falls and fractures. Anxiety and fear of falling limited her mobility, and she sustained a sacral pressure ulcer during acute hospitalization. On admission, history was remarkable for unsteady gait and muscle cramps exacerbated when startled or excited. Examination was remarkable for rigidity in her axial and limb muscles. She presented …

Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …

Early And Late Treatment Of Migraine With Dhe Ns (Migranal®), Meryl Latsko, Md, Mph, Stephen D. Silberstein, Md

Department of Jefferson Headache Center Papers and Presentations

To examine the use of DHE NS (Migranal®) in the early and late treatment of migraine in subjects with a history of cutaneous allodynia.

Obesity And Cancer, Rickie Brawer, Phd, Mph, Nancy Brisbon, Md, James Plumb, Md

Department of Family & Community Medicine Faculty Papers

Obesity has become the second leading preventable cause of disease and death in the United States, trailing only tobacco use. Weight control, dietary choices, and levels of physical activity are important modifiable determinants of cancer risk. If multi-factorial approaches to prevention and management are not implemented, obesity will likely become the leading modifiable cause of death in the coming years. Physicians have a key role in integrating these approaches into clinical care and advocating for systemic prevention efforts. This article provides: 1) an introduction to the epidemiology and magnitude of childhood and adult obesity; 2) the relationship of overweight/obesity to …