Digital Commons Network^™

Reducing Lung Disease In Cystic Fibrosis: Model Systems And Anti-Inflammatory Treatment, Scotty Mcglothlin Buff

MUSC Theses and Dissertations

Cystic fibrosis (CF), the most common lethal autosomal recessive disease in Caucasians resulting in a median life span of approximately 35 years, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The primary cause of morbidity and mortality is respiratory failure caused by progressive obstructive lung disease. CF airway disease is characterized by the abundance of pro inflammatory cells, chemokines and cytokines with a deficiency of regulatory/anti-inflammatory cytokine interleukin 10 (lL10). We hypothesized that CF airway obstruction originates from excessive inflammation and gene transfer of IL-I0 would decrease inflammation in the airways of mice infected with Pseudomonas …

Long-Distance Three-Color Neuronal Tracing In Fixed Tissue Using Neurovue Dyes, Heather Jensen Smith, Brian Gray, Katharine Muirhead, Betsy Ohlsson-Wilhelm, Bernd Fritzsch

Journal Articles: Eppley Institute

Dissecting development of neuronal connections is critical for understanding neuronal function in both normal and diseased states. Charting the development of the multitude of connections is a monumental task, since a given neuron typically receives hundreds of convergent inputs from other neurons and provides divergent outputs for hundreds of other neurons. Although progress is being made utilizing various mutants and/or genetic constructs expressing fluorescent proteins like GFP, substantial work remains before a database documenting the development and final location of the neuronal pathways in an adult animal is completed. The vast majority of developing neurons cannot be specifically labeled with …

Mapping Exercise Of Mental Health Research And Researchers In Pakistan, Haider A. Naqvi, Murad M. Khan

Department of Psychiatry

Objective: To systematically identify mental health research and researchers in Pakistan. Subsidiary objectives were to identify methodologies of studies published in the indexed journals along with their country wide mean impact factor.
Methods: A systematic search strategy using key words related to neuropsychiatry was carried out to identify various studies published in Indexed and Non-indexed databases.
Results: We identified 108 studies from Indexed data bases (77.8% Medline; 22.2% PsychInfo). Beside these, 51 studies were also identified from non-indexed databases. Among the indexed articles, 97 (89.8%) were Journal articles while 10 were other type of documents--there were 3 clinical trials of …

The Status Of Childhood Lead Poisoning And Prevention In Nevada, Usa, Anne Rothweiler, Elena E. Cabb, Shawn Gerstenberger

Environmental & Global Health Faculty Research

One of the first steps in addressing the problem of childhood lead poisoning is to identify the possible sources of exposure in specific communities and target high-risk populations with appropriate interventions. Due to several factors, such as lack of funding and lack of blood lead reporting, little information exists regarding the occurrence of childhood lead poisoning and the prevalence of potential exposure sources in the state of Nevada. Following the recent establishment of a Nevada-based Lead Poisoning Program, we compiled the most current information available on Nevadans, and use this knowledge to suggest future research objectives and outreach activities for …

A Model Of Late Long-Term Potentiation Simulates Aspects Of Memory Maintenance, Paul Smolen

Faculty, Staff and Student Publications

Late long-term potentiation (L-LTP) denotes long-lasting strengthening of synapses between neurons. L-LTP appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing ongoing activity and biochemical pathways important for L-LTP. In this study, ongoing activity was incorporated into two such models - …

Labrad : Vol 32, Issue 1 - January 2007, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• T-Cell Receptor (TcR) Gene Rearrangement Studies: A Useful Adjunct for the Diagnosis of T-Cell Lymphoproliferative Disorders
• Vitamin D Measurement
• Quiz
• Ristocetin Cofactor Activity
• Portal Biliopathy- An Uncommon Cause of Biliary Obstruction
• Laboratory Diagnosis of Hepatitis C: Transition from Serological to Molecular Methods
• Answer to Quiz
• Dengue Fever
• Bone Densitometry (DEXA Scanning) in the Diagnosis of Osteoporosis
• Western Blot for HIV 1 Virus
• 8th Sheffield International Conference - Diagnostic Imaging

Oncolog, Volume 52, Number 12, December 2007, Sunni Hosemann, Diane Witter, Huong Le-Petross Md

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Worth More than a Thousand Words\
• A Step Forward for Stents
• House Call: Getting the Most From Your Doctor Visit
• DiaLog: Is MRI Better for Breast Screening?, by Huong Le-Petross, MD

Secondary Surfactant Dysfunction And Deficiency, Robin Louise Bissinger

MUSC Theses and Dissertations

Based on literature in Adult Respiratory Distress Syndrome in humans and evidence of surfactant activation in vitro and vivo, and our clinical observations of secondary respiratory decompensation in premature infancies recovering from RDS, a study was designed to look at the possibility of benefit from secondary surfactant administration in premature infancies with secondary decompensation after recovery from respiratory distress syndrome (RDS). A prospective pilot study was performed to study the effects of secondary surfactant administration on oxygenation, ventilation and pulmonary function of neonates who had respiratory decompensation after recovery from RDS. A secondary data analysis was performed looking at pulmonary …

Gastroesophageal Reflux Disease And Fundoplication In Infants And Children, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

Gastroesophageal reflux disease (GERD) can be one of the most distressing conditions developing at different ages in infants and children. The disease itself is a complex process along with ongoing dynamic anatomic and physiologic changes occurring during normal development. Therefore among referring physicians, considerations regarding the role of surgery for GERD in children varies widely depending on individual experiences in managing these patients. These varied opinions result in discrepancies in the operative experience with fundoplication among pediatric surgeons. It is unclear how much of the current opinions stem from published evidence, particularly with regard to the safety and efficacy of …

A Turner Syndrome Neurocognitive Phenotype Maps To Xp22.3., Andrew R Zinn, David Roeltgen, Gerry Stefanatos, Purita Ramos, Frederick F Elder, Harvey Kushner, Karen Kowal, Judith L Ross

Department of Pediatrics Faculty Papers

BACKGROUND: Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47) of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. METHODS: Subjects were recruited from North American genetics and …

Department Of Pathology, Thomas Jefferson University, Identification Of Conserved Gene Expression Features Between Murine Mammary Carcinoma Models And Human Breast Tumors., Jason I Herschkowitz, Karl Simin, Victor J Weigman, Igor Mikaelian, Jerry Usary, Zhiyuan Hu, Karen E Rasmussen, Laundette P Jones, Shahin Assefnia, Subhashini Chandrasekharan, Michael G Backlund, Yuzhi Yin, Andrey I Khramtsov, Roy Bastein, John Quackenbush, Robert I Glazer, Powel H Brown, Jeffrey E Green, Levy Kopelovich, Priscilla A Furth, Juan P Palazzo, Olufunmilayo I Olopade, Philip S Bernard, Gary A Churchill, Terry Van Dyke, Charles M Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of …

Lateral Wall Protein Content Mediates Alterations In Cochlear Outer Hair Cell Mechanics Before And After Hearing Onset, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

Specialized outer hair cells (OHCs) housed within the mammalian cochlea exhibit active, nonlinear, mechanical responses to auditory stimulation termed electromotility. The extraordinary frequency resolution capacity of the cochlea requires an exquisitely equilibrated mechanical system of sensory and supporting cells. OHC electromotile length change, stiffness, and force generation are responsible for a 100-fold increase in hearing sensitivity by augmenting vibrational input to non-motile sensory inner hair cells. Characterization of OHC mechanics is crucial for understanding and ultimately preventing permanent functional deficits due to overstimulation or as a consequence of various cochlear pathologies. The OHCs' major structural assembly is a highly-specialized lateral …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Lupine Allergy: Not Simply Cross-Reactivity With Peanut Or Soy, Kim A. B. M. Peeters, Julie A. Nordlee, André H. Penninks, Lingyun Chen, Richard E. Goodman, Carla A. F. M. Bruijnzeel-Koomen, Sue L. Hefle, Steve L. Taylor, André C. Knulst

Department of Food Science and Technology: Faculty Publications

Background: Reports of lupine allergy are increasing as its use in food products increases. Lupine allergy might be the consequence of cross-reactivity after sensitization to peanut or other legumes or de novo sensitization. Lupine allergens have not been completely characterized.

Objectives: We sought to identify allergens associated with lupine allergy, evaluate potential cross-reactivity with peanut, and determine eliciting doses (EDs) for lupine allergy by using double-blind, placebo-controlled food challenges.

Methods: Six patients with a history of allergic reactions to lupine flour were evaluated by using skin prick tests, CAP tests, and double-blind, placebo-controlled food challenges. Three of …

Reduction Of Astrogliosis And Microgliosis By Cerebrospinal Fluid Shunting In Experimental Hydrocephalus, Janet M. Miller, James P. Mcallister Ii

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Reactive gliosis has the potential to alter biomechanical properties of the brain, impede neuronal regeneration and affect plasticity. Determining the onset and progression of reactive astrogliosis and microgliosis due to hydrocephalus is important for designing better clinical treatments.

Methods

Reactive astrogliosis and microgliosis were evaluated as the severity of hydrocephalus increased with age in hydrocephalic H-Tx rats and control littermates. Previous studies have suggested that gliosis may persist after short-term drainage (shunt treatment) of the cerebrospinal fluid. Therefore shunts were placed in 15d hydrocephalic rats that were sacrificed after 6d (21d of age) or after 21d (36d of …

Genome Sequence Of Fusobacterium Nucleatum Subspecies Polymorphum — A Genetically Tractable Fusobacterium, Sandor E Karpathy, Xiang Qin, Jason Gioia, Huaiyang Jiang, Yamei Liu, Joseph F Petrosino, Shailaja Yerrapragada, George E Fox, Susan Kinder Haake, George M Weinstock, Sarah K Highlander

Faculty, Staff and Student Publications

Fusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique …

Nosocomial Buffalopoxvirus Infection, Karachi, Pakistan, Afia Zafar, Robert Swanepoel, Roger Hewson, Mazhar Nizam, Altaf Ahmed, Akhtar Husain, Antoinette Grobbelaar, Kevin Bewley, Valerie Mioulet, Barry Dowsett, Linda Easterbrook, Rumina Hasan

Department of Pathology and Laboratory Medicine

During 5 months in 2004–2005, buffalopoxvirus infection, confirmed by virus isolation and limited nucleic acid sequencing, spread between 5 burns units in Karachi, Pakistan. The outbreak was related to movement of patients between units. Control measures reduced transmission, but sporadic cases continued due to the admission of new patients with community-acquired infections.

All In The Family: Atypical Hsp70 Chaperones Are Conserved Modulators Of Hsp70 Activity, Lance Shaner, Kevin A Morano

Faculty, Staff and Student Publications

Divergent relatives of the Hsp70 protein chaperone such as the Hsp110 and Grp170 families have been recognized for some time, yet their biochemical roles remained elusive. Recent work has revealed that these "atypical" Hsp70s exist in stable complexes with classic Hsp70s where they exert a powerful nucleotide-exchange activity that synergizes with Hsp40/DnaJ-type cochaperones to dramatically accelerate Hsp70 nucleotide cycling. This represents a novel evolutionary transition from an independent protein-folding chaperone to what appears to be a dedicated cochaperone. Contributions of the atypical Hsp70s to established cellular roles for Hsp70 now must be deciphered.

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Jefferson Journal of Psychiatry

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Psychiatric Diagnoses In Patients With Williams Syndrome And Their Families, Janet C. Kennedy M.D. (Pgy1), David L. Kaye M.D., Laurie S. Sadler M.D.

Jefferson Journal of Psychiatry

Williams Syndrome (WS) is a genetic disorder associated with mental retardation (MR) and a distinct behavioral phenotype including a friendly and outgoing personality. This population, like others with MR, has been reported to have an increased rate of symptoms of mental illness; however, few studies have used DSM-IV criteria to quantify specific psychiatric diagnoses in WS and the prevalence of psychiatric illness in relatives of individuals with WS and the possible relationship between family and patient diagnoses is currently unknown.

Methods: Twenty-one families participated; the patients’ average age was 16 years. DSM-IV diagnoses were applied by using the Anxiety …

Acute And Chronic Methylphenidate Dose-Response Assessment On Three Adolescent Male Rat Strains, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to …

Towards A Cure For Traumatic Paraplegia - Is There Cause For Hope?, Rashid Jooma

Section of Neurosurgery

In the past decade, great strides have been made in the field of CNS tissue repair and expectations have been raised that a cure of spinal paralysis is at hand. The two broad categories of investigational approaches to spinal regeneration are: (1) Enhancing the Regenerative Milieu of the Cord and (2) Cellular and Tissue Transplantation. Amongst the latter approaches, the early use of foetal cord tissue has given way to the more sophisticated studies on stem cell therapy and the implants of olfactory ensheating cells. These have engendered considerable public interest and are being offered as commercially available therapies in …

Atomoxetine Treatment In Children And Adolescents With Attention-Deficit Hyperactivity Disorder: What Are The Long-Term Health-Related Quality-Of-Life Outcomes?, Amy R. Perwien, Christopher J. Kratochvil, Douglas E. Faries, Brigette S. Vaughan, Thomas Spencer, Ronald T. Brown

Journal Articles: Psychiatry

OBJECTIVE: Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) in children. However, relatively few studies have addressed the impact of treatment on long-term subjective, psychosocial outcomes, such as health-related quality of life (HRQL). This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD.

METHODS: Participants included 6- to 17-year-old children and adolescents (n = 912) with ADHD enrolled in a 24-month, multicenter, open-label trial of atomoxetine. Outcomes included clinician ratings of ADHD, parent ratings of ADHD, and a widely used measure of HRQL (The Child Health …

An In Vitro Model Of Ovarian Cancer: Studying The Effects Of Talc And Pycnogenol®, Amber Renée Buz'zard

Loma Linda University Electronic Theses, Dissertations & Projects

Ovarian cancer is the sixth most common cancer and accounts for more deaths than any other cancer of the female reproductive system. The American Cancer Society has suggested that poor diet, talc and industrial pollutants may increase the risk of developing ovarian cancer. Talc is ubiquitous and concern is raised about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. Due to the silent nature of ovarian cancer, chemoprevention is a high priority. The most useful chemopreventive compounds will inhibit, delay or reverse carcinogenesis, and can be taken for long periods of time with …

Proteomic Identification Of In Vivo Substrates For Matrix Metalloproteinases 2 And 9 Reveals A Mechanism For Resolution Of Inflammation, Kendra J Greenlee, David B Corry, David A Engler, Risë K Matsunami, Philippe Tessier, Richard G Cook, Zena Werb, Farrah Kheradmand

Faculty, Staff and Student Publications

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic …

Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst

Dartmouth Scholarship

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …

Altered Placental And Fetal Expression Of Igfs And Igf-Binding Proteins Associated With Intrauterine Growth Restriction In Fetal Sheep During Early And Mid-Pregnancy., Barbra De Vrijer, Meredith L Davidsen, Randall B Wilkening, Russell V Anthony, Timothy Regnault

Paediatrics Publications

The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT …

The Role Of Allograft Inflammatory Factor 1 In Systemic Sclerosis, Francesco Del Galdo, Carol M. Artlett, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

ABSTRACT

Purpose: To review studies which support the hypothesis that allograft inflammatory factor-1 (AIF-1), a protein initially identified in chronically rejected cardiac allografts, may be involved in the pathogenesis of the progressive fibroproliferative vasculopathy which is a hallmark of systemic sclerosis (SSc).

Recent findings: Recent findings demonstrated elevated AIF-1 expression both in SSc affected tissues and peripheral blood mononuclear cells. A detailed immunohistopathologic study examined the tissue and cellular localization of the protein in affected SSc tissues and demonstrated its expression in the endothelium of dermal and pulmonary vessels, in the pulmonary parenchyma, and in relevant inflammatory cells including T …

Mechanism Of Neuronal Injury In Cerebral Venous Thrombosis, Uzma Usman, Mohammad Wasay

Department of Medicine

The impact of CVT on the brain is wide spectrum, ranging from completely normal parenchyma to brain oedema and/or haemorrhage. Multiple factors relate to neuronal injury in CVT including; dural sinus pressure, increased venous flow velocities, collateralization of venous channels, rate of occlusion, development of cytotoxic and vasogenic oedema, recanalization and accelerated myelination. It is suggested that recanalization of occluded vein, as well as, the presence or absence and the efficiency of intracranial venous collaterals, may have an impact on the extent of brain tissue damage and hence the prognosis of acute CVT.