Digital Commons Network^™

Cx3cl1 Reduces Neurotoxicity And Microglial Activation In A Rat Model Of Parkinson's Disease, Mibel M. Pabon, Adam D. Bachstetter, Charles E. Hudson, Carmelina Gemma, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1), produced by neurons, suppresses the activation of microglia. CX3CL1 …

Participating In A Community Of Learners Enhances Resident Perceptions Of Learning In An E-Mentoring Program: Proof Of Concept, Timona Obura, William. E. Brant, Fiona Miller, I. J. Parboosingh

Obstetrics and Gynaecology, East Africa

Background

Community learning and e-mentoring, learning methods used in higher education, are not used to any extent in residency education. Yet both have the potential to enhance resident learning and, in the case of community learning, introduce residents to basic lifelong learning skills. We set out to determine whether residents participating in an Internet based e-mentoring program would, with appropriate facilitation, form a community of learners (CoL) and hold regular community meetings. We also determined resident and faculty perceptions of CoL and Internet sessions as effective learning experiences.

Methods

A six-month e-mentoring pilot was offered to 10 Radiology residents in …

Incidence And Impact Of Baseline Electrolyte Abnormalities In Patients Admitted With Chemotherapy Induced Febrile Neutropenia., Asim Jamal Shaikh, Samira Ahmed Bawany, Nehal Masood, Ausaf Ahmed Khan, Ahmed Nadeem Abbasi, Syed Najeeb Niamutullah, Adnan Zaidi, Salman Adil, Shiyam Kumar

Section of Haematology/Oncology

Background: Febrile neutropenia (FN) and myelosupression remain a challenging oncologic medical emergency and dose limiting toxicity associated with chemotherapy for cancers. Various factors are known to affect the outcomes for Patients diagnosed with FN. Electrolyte abnormalities have commonly been observed, but the real incidence and their impact has been only scarcely studied in literature. Methods: This was a prospective, observational study. A total of two hundred and fifteen (215) Patients admitted between January 2007 and August 2008 were included. Analysis of data was made using SPSS version16.0. Toxicity profile was graded according to CTC version 3.0. Results: Almost equal number …

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.

PRINCIPAL FINDINGS: Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no …

Cilostazol Versus Aspirin For Secondary Prevention Of Vascular Events After Stroke Of Arterial Origin, Ayeesha Kamran Kamal, Imama Naqvi, Muhammad R Husain, Bhojo A Khealani

Section of Neurology

Background:Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke. ObjectiveS: To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in Patients at high vascular risk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 …

Correcting Mortality For Loss To Follow-Up: A Nomogram Applied To Antiretroviral Treatment Programmes In Sub-Saharan Africa, Matthias Egger, Ben D. Spycher, John Sidle, Ralf Weigel, Elvin H. Geng, Matthew P. Fox, Patrick Macphail, Gilles Van Custem, Eugene Messou, Robin Wood, Denis Nash, Margaret Pascoe, Diana Dickinson

Publications and Research

Background

The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.

Methods and Findings

We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in …

A Test Of The Role Of The Medial Temporal Lobe In Single-Word Decoding., Karol Osipowicz, Tyler Rickards, Atif Shah, Ashwini Sharan, Michael Sperling, Waseem Kahn, Joseph Tracy

Department of Neurology Faculty Papers

The degree to which the MTL system contributes to effective language skills is not well delineated. We sought to determine if the MTL plays a role in single-word decoding in healthy, normal skilled readers. The experiment follows from the implications of the dual-process model of single-word decoding, which provides distinct predictions about the nature of MTL involvement. The paradigm utilized word (regular and irregularly spelled words) and pseudoword (phonetically regular) stimuli that differed in their demand for non-lexical as opposed lexical decoding. The data clearly showed that the MTL system was not involved in single word decoding in skilled, native …

Neuroinflammation Leads To Region-Dependent Alterations In Astrocyte Gap Junction Communication And Hemichannel Activity., Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, …

Population-Wide Model-Free Quantification Of Blood-Brain-Barrier Dynamics In Multiple Sclerosis, Russell T. Shinohara, Ciprian Crainiceanu, Brian Caffo, María Inés Gaitán, Daniel Reich

Johns Hopkins University, Dept. of Biostatistics Working Papers

The processes by which new white matter lesions in multiple sclerosis (MS) develop are only partially understood. Much of this understanding has come through magnetic resonance imaging (MRI) of the human brain. One of the hallmarks of new lesion development in MS is enhancement on T1-weighted MRI scans following the intravenous administration of a gadolinium-based contrast agent that shortens the longitudinal relaxation time of the tissue. This visible enhancement in the MRI results from the opening of the blood-brain barrier and reveals areas of active inflammation. The incidence and number of existing enhancing lesions are common outcome measures used in …

Molecular Mechanism By Which The Nucleoid Occlusion Factor, Slma, Keeps Cytokinesis In Check, Nam Ky Tonthat, Stefan T Arold, Brian F Pickering, Michael W Van Dyke, Shoudan Liang, Yue Lu, Tushar K Beuria, William Margolin, Maria A Schumacher

Faculty, Staff and Student Publications

In Escherichia coli, cytokinesis is orchestrated by FtsZ, which forms a Z-ring to drive septation. Spatial and temporal control of Z-ring formation is achieved by the Min and nucleoid occlusion (NO) systems. Unlike the well-studied Min system, less is known about the anti-DNA guillotining NO process. Here, we describe studies addressing the molecular mechanism of SlmA (synthetic lethal with a defective Min system)-mediated NO. SlmA contains a TetR-like DNA-binding fold, and chromatin immunoprecipitation analyses show that SlmA-binding sites are dispersed on the chromosome except the Ter region, which segregates immediately before septation. SlmA binds DNA and FtsZ simultaneously, and the …

Fluorine Substitutions In An Antigenic Peptide Selectively Modulate T Cell Receptor Binding In A Minimally Perturbing Manner, Kurt H. Piepenbrink, Oleg Y. Borbulevych, Ruth F. Sommese, John Clemens, Kathrynq M. Armstrong, Clare Desmond, Priscilla Do, Brian M. Baker

Food for Health: Publications

T cell receptor (TCR) recognition of antigenic peptides bound and presented by major histocompatibility complex (MHC) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide/MHC molecules weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Further, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. Here, we studied how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we …

Noncoronary Cardiac Abnormalities Are Associated With Coronary Artery Dilation And With Laboratory Inflammatory Markers In Acute Kawasaki Disease., Beth F. Printz, Lynn A. Sleeper, Jane W. Newburger, L Luann Minich, Timothy Bradley, Meryl S. Cohen, Deborah Frank, Jennifer S. Li, Renee Margossian, Girish S. Shirali, Masato Takahashi, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: We explored the association of noncoronary cardiac abnormalities with coronary artery dilation and with laboratory inflammatory markers early after Kawasaki disease (KD) diagnosis.

BACKGROUND: Left ventricular (LV) dysfunction, mitral regurgitation (MR), and aortic root dilation occur early after diagnosis; their associations with coronary artery dilation and inflammatory markers have not been well-described.

METHODS: Centrally interpreted echocardiograms were obtained at KD diagnosis and 1 and 5 weeks after diagnosis on 198 subjects in the National Institutes of Health-sponsored Pediatric Heart Network KD pulsed steroid trial. Regression models were constructed to investigate the relationships among early LV dysfunction, MR, and aortic …

Short-Term And Long-Term Effects Of Orthopedic Biodegradable Implants, Ami R. Amini, James S. Wallace, Syam P. Nukavarapu

Articles - Patient Care

Presently, orthopedic and oral/maxillofacial implants represent a combined $2.8 billion market, a figure expected to experience significant and continued growth. Although traditional permanent implants have been proved clinically efficacious, they are also associated with several drawbacks, including secondary revision and removal surgeries. Non-permanent, biodegradable implants offer a promising alternative for patients, as they provide temporary support and degrade at a rate matching tissue formation, and thus, eliminate the need for secondary surgeries. These implants have been in clinical use for nearly 25 years, competing directly with, or maybe even exceeding, the performance of permanent implants. The initial implantation of biodegradable …

Teens Texting And Consequences: A Brief Review, Archana Srinivas, Megan White, Hatim A. Omar

Pediatrics Faculty Publications

The aim of this paper is to summarize the current literature on texting use amongst adolescents. A brief overview will be presented on the prevalence of texting among teenagers, the use of texting for sexting and cyberbullying as well as the dangers of texting while driving. This paper will serve as a brief overview of these topics in order to bring to light the emerging challenges that texting presents to the mental and physical well-being of adolescents in an effort to evoke further discussion regarding the need for increasing awareness and education to parents, educators, law makers and health care …

Anti-Saccade Performance Predicts Executive Function And Brain Structure In Normal Elders, J. B. Mirsky, H. W. Heuer, A. Jafari, J. H. Kramer, A. K. Schenk, Indre Viskontas, B. L. Miller, A. L. Boxer

Psychology

Objective—To assess the neuropsychological and anatomical correlates of anti-saccade (AS) task performance in normal elders.

Background—The AS task correlates with neuropsychological measures of executive function and frontal lobe volume in neurological diseases, but has not been studied in a well-characterized normal elderly population. Because executive dysfunction can indicate an increased risk for cognitive decline in cognitively normal elders, we hypothesized that AS performance might be a sensitive test of age-related processes that impair cognition.

Method—The percentage of correct AS responses was evaluated in forty-eight normal elderly subjects and compared with neuropsychological test performance using linear regression analysis …

Multimodal Cuing Of Autobiographical Memory In Semantic Dementia, D. L. Greenberg, J. M. Ogar, Indre Viskontas, M. L. Gorno Tempini, B. Miller, B. J. Knowlton

Psychology

OBJECTIVE: Individuals with semantic dementia (SD) have impaired autobiographical memory (AM), but the extent of the impairment has been controversial. According to one report (Westmacott, Leach, Freedman, & Moscovitch, 2001), patient performance was better when visual cues were used instead of verbal cues; however, the visual cues used in that study (family photographs) provided more retrieval support than do the word cues that are typically used in AM studies. In the present study, we sought to disentangle the effects of retrieval support and cue modality.

METHOD: We cued AMs of 5 patients with SD and 5 controls with words, simple …

Genetic Analysis Of The Neurosteroid Deoxycorticosterone And Its Relation To Alcohol Phenotypes: Identification Of Qtls And Downstream Gene Regulation, Patrizia Porcu, Todd K. O'Buckley, Soomin C. Song, Jo Lynne Harenza, Lu Lu, Xusheng Wang, Michael F. Miles, A. Leslie Morrow

Neurology Publications

Background

Deoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3α,5α)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence.

Methodology/Principal Findings

To systematically define the genetic basis, regulation, and behavioral significance of DOC levels in plasma and cerebral cortex we examined such levels across 47 young adult males from C57BL/6J (B6)×DBA/2J (D2) (BXD) mouse strains for quantitative trait loci (QTL) and bioinformatics analyses of behavior and gene regulation. Mice were injected with saline …

Fto And Mc4r Gene Variants Are Associated With Obesity In Polycystic Ovary Syndrome, Kathryn G. Ewens, Michelle R. Jones, Wendy Ankener, Douglas R. Stewart, Margrit Urbanek, Andrea Dunaif, Richard S. Legro, Angela Chua, Ricardo Azziz, Richard S. Spielman, Mark O. Goodarzi, Jerome F. Strauss Iii

Obstetrics and Gynecology Publications

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one …

Com Outlook Winter 2011, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Medical Education Digest, Vol. 13 No. 1 (January/February 2011), Nova Southeastern University

Medical Education Digest

No abstract provided.

Chemotherapy-Induced Cognitive Impairment Is Associated With Decreases In Cell Proliferation And Histone Modifications, Teresita L. Briones, Julie Woods

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In this study, we examined the effects of cyclophosphamide, methothrexate, and 5-Fluorouracil (CMF) drug combination on various aspects of learning and memory. We also examined the effects of CMF on cell proliferation and chromatin remodeling as possible underlying mechanisms to explain chemotherapy-associated cognitive dysfunction. Twenty-four adult female Wistar rats were included in the study and had minimitter implantation for continuous activity monitoring two weeks before the chemotherapy regimen was started. Once baseline activity data were collected, rats were randomly assigned to receive either CMF or saline injections given intraperitoneally. Treatments were given once a week for a total …

Activating Mutation In Met Oncogene In Familial Colorectal Cancer, Deborah W. Neklason, Michelle W. Done, Nykole R. Sargent, Ann G. Schwartz, Hoda Anton-Culver, Constance A. Griffin, Dennis J. Ahnen, Joellen M. Schildkraut, Gail E. Tomlinson, Louise C. Strong, Alexander R. Miller, Jill E. Stopfer, Randall W. Burt

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility.

Methods

MET exons …

High-Frequency Ultrasound For Intraoperative Margin Assessments In Breast Conservation Surgery: A Feasibility Study, Timothy E. Doyle, Rachel E. Factor, Christina L. Ellefson, Kristina M. Sorensen, Brady J. Ambrose, Jeffrey B. Goodrich, Vern P. Hart, Scott C. Jensen, Hemang Patel, Leigh A. Neumayer

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In addition to breast imaging, ultrasound offers the potential for characterizing and distinguishing between benign and malignant breast tissues due to their different microstructures and material properties. The aim of this study was to determine if high-frequency ultrasound (20-80 MHz) can provide pathology sensitive measurements for the ex vivo detection of cancer in margins during breast conservation surgery.

Methods

Ultrasonic tests were performed on resected margins and other tissues obtained from 17 patients, resulting in 34 specimens that were classified into 15 pathology categories. Pulse-echo and through-transmission measurements were acquired from a total of 57 sites on the …

Fetal Erap2 Variation Is Associated With Preeclampsia In African Americans In A Case-Control Study, Lori D. Hill, Dashaunda D. Hilliard, Timothy P. York, Sindhu Srinivas, Juan P. Kusanovic, Ricardo Gomez, Michal A. Elovitz, Roberto Romero, Jerome F. Strauss Iii

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia …

The Cns Microvascular Pericyte: Pericyte-Astrocyte Crosstalk In The Regulation Of Tissue Survival, Drew Bonkowski, Vladimir Katyshev, Roumen D. Balabanov, Andre Borisov, Paula Dore-Duffy

Wayne State University Associated BioMed Central Scholarship

Abstract

The French scientist Charles Benjamin Rouget identified the pericyte nearly 140 years ago. Since that time the role of the pericyte in vascular function has been difficult to elucidate. It was not until the development of techniques to isolate and culture pericytes that scientists have begun to understand the true impact of this unique cell in the maintenance of tissue homeostasis. In the brain the pericyte is an integral cellular component of the blood-brain barrier and, together with other cells of the neurovascular unit (endothelial cells, astrocytes and neurons) the pericyte makes fine-tuned regulatory adjustments and adaptations to promote …

Noninvasive Ventilation In Acute Respiratory Failure Due To H1n1 Influenza: A Word Of Caution, A. Singh, J. Singh

Journal Articles

No abstract provided.

Inside And Out: An Epicardial Lead Gone Astray, S. N. Hong, B. Rosenzweig, G. A. Crooke, I. Kronzon, M. B. Srichai

Journal Articles

No abstract provided.

Safety And Efficacy Of Abt-089 In Pediatric Attention-Deficit/Hyperactivity Disorder: Results From Two Randomized Placebo-Controlled Clinical Trials., Timothy E. Wilens, Laura M. Gault, Ann Childress, Christopher J. Kratochvil, Lindsey Bensman, Coleen M. Hall, Evelyn Olson, Weining Z. Robieson, Tushar S. Garimella, Walid M. Abi-Saab, George Apostol, Mario D. Saltarelli

Journal Articles: Psychiatry

OBJECTIVE: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).

METHOD: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home …

Microrna-183 Family Expression In Hair Cell Development And Requirement Of Micrornas For Hair Cell Maintenance And Survival, Michael D. Weston, Marsha L. Pierce, Heather Jensen Smith, Bernd Fritzsch, Sonia Rocha-Sanchez, Kirk W. Beisel, Garrett A. Soukup

Journal Articles: Eppley Institute

MicroRNAs (miRNAs) post-transcriptionally repress complementary target gene expression and can contribute to cell differentiation. The coordinate expression of miRNA-183 family members (miR-183, miR-96, and miR-182) has been demonstrated in sensory cells of the mouse inner ear and other vertebrate sensory organs. To further examine hair cell miRNA expression in the mouse inner ear, we have analyzed miR-183 family expression in wild type animals and various mutants with defects in neurosensory development. miR-183 family member expression follows neurosensory cell specification, exhibits longitudinal (basal-apical) gradients in maturating cochlear hair cells, and is maintained in sensory neurons and most hair cells into adulthood. …

The Living Textbook Project For Affordable Higher Education, Dayanjan S. Wijesinghe

Surgery Presentations

A blue print for ensuring that community college education remains affordable to the future generations via elimination of the cost of textbooks.