Digital Commons Network^™

Prostaglandin E(2) Is Crucial In The Response Of Podocytes To Fluid Flow Shear Stress., Tarak Srivastava, Ellen T. Mccarthy, Ram Sharma, Patricia A. Cudmore, Mukut Sharma, Mark L. Johnson, Lynda F. Bonewald

Manuscripts, Articles, Book Chapters and Other Papers

Podocytes play a key role in maintaining and modulating the filtration barrier of the glomerulus. Because of their location, podocytes are exposed to mechanical strain in the form of fluid flow shear stress (FFSS). Several human diseases are characterized by glomerular hyperfiltration, such as diabetes mellitus and hypertension. The response of podocytes to FFSS at physiological or pathological levels is not known. We exposed cultured podocytes to FFSS, and studied changes in actin cytoskeleton, prostaglandin E(2) (PGE(2)) production and expression of cyclooxygenase-1 and-2 (COX-1, COX-2). FFSS caused a reduction in transversal F-actin stress filaments and the appearance of cortical actin …

The Risks And Benefits Of Long-Term Use Of Hydroxyurea In Sickle Cell Anemia: A 17.5 Year Follow-Up., M. H. Steinberg, W. F. Mccarthy, O. Castro, S. K. Ballas, F. D. Armstrong, W. Smith, K. Ataga, P. Swerdlow, A. Kutlar, L. Decastro, M. A. Waclawiw, E. Orringer, S. Jones, D. Strayhorn, W. Rosse, G. Phillips, D. Pearce, A. Johnson-Telfair, L. Daitch, P. Milner, A. Tracy, S. Valdez, G. E. Allen, J. Moshang, B. Scott, C. Bigelow, A. Anderson, V. Sabahi, T. Harrington, W. Labrousse, C. Pegelow, D. Temple, E. Case, R. Harrell, S. Childerie, S. Embury, B. Schmidt, D. Davies, Y. Saunthararajah, M. Koshy, N. Talischy-Zahed, L. Dorn, G. Pendarvis, M. Mcgee, M. Telfer, A. Davis, O. C. Onyekwere, C. Nwokolo, H. Finke, E. Perlin, J. Siteman, M. Bryan, T. Saunders, Y. Barber, P. Gascon, P. Di Paolo, S. Gargiulo, J. Eckman, E. Carter-Randall, J. H. Bailey, A. Platt, L. Waller, G. Ramirez, V. Knors, S. Hernandez, E. M. Rodriguez, E. Wilkes, E. Vichinsky, W. Hagar, C. Hoehner, E. Hackney-Stevens, S. Claster, A. Earles, K. Kleman, K. Mclaughlin, L. White, B. Maddox, L. Usry, A. Brenner, K. Williams, R. O'Brien, K. Genther, S. Shurin, B. Berman, K. Chiarucci, L. Keverline, N. Olivieri, J. Chow, M. Hui, D. Shaw, N. Lewis, M. Okam, E. Mandell, A. Palmer, K. Bridges, B. Tynan, C. Winograd, R. Bellevue, H. Dosik, M. Sheikhai, P. Ryans, H. Souffrant, B. Adler, A. Johnson-Telfair, L. Eskridge, J. Prchal, J. Braddock, T. Mcardle, T. Carlos, A. Roundtree-Schmotzer, D. Gardner

Department of Medicine Faculty Papers

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality.

Reducing The Effects Of Intracellular Accumulation Of Thermolabile Collagen Ii Mutants By Increasing Their Thermostability In Cell Culture Conditions., Katarzyna Gawron, Deborah A. Jensen, Andrzej Steplewski, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Mutations in collagen II are associated with spondyloepiphyseal dysplasia, a group of heritable diseases whose common features include aberrations of skeletal growth. The mechanisms through which mutations in collagen II affect the cartilaginous tissues are complex and include both intracellular and extracellular processes. One of those mechanisms involves cellular stress caused by excessive accumulation of misfolded collagen II mutants. We investigated whether stabilizing the structure of thermolabile R789C and R992C collagen II mutants would improve their secretion from cells, thereby reducing cellular stress and apoptosis. Employing glycerol and trimethylamine N-oxide (TMAO), chemicals that increase the thermostability of collagen triple helices, …

Reduction Of Sympathetic Activity Via Adrenal-Targeted Grk2 Gene Deletion Attenuates Heart Failure Progression And Improves Cardiac Function After Myocardial Infarction., Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Steven N. Ebert, Gerald W. Dorn, Walter J. Koch

Department of Medicine Faculty Papers

Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells …

The Conundrum Of Sensitization When Recording From Nociceptors, Geoffrey M. Bove, Andrew Dilley

Biomedical Sciences Faculty Publications

Nociceptors are sensory neurons that detect harmful, or potentially harmful, stimuli, and can become sensitized following injury or repetitive stimulation. When sensitized, nociceptors often exhibit activity in the absence of apparent or additional stimulation, called ongoing (or spontaneous) activity (OA). In this report, we provide evidence that OA in nociceptors can be caused by the stimuli typically used to identify and characterize the neuron, which must by definition be noxious and therefore potentially sensitizing. Such OA caused by the experimental methodology can confound interpretation. In our nerve inflammation model, OA can potentially arise from multiple sites, including the lesion site …

A Passive Pure Moment Protocol For Testing Spine Segments: Development And Application, Kyle David Fraysur

Theses and Dissertations (ETD)

The pure moment protocol is the accepted standard for performing in-vitro biomechanical testing of spinal devices. Published studies predominantly report range of motion and flexibility data, but information regarding the segment center of rotation is also relevant. Most current pure moment platforms are not sensitive enough to accurately calculate the instantaneous axis of rotation (IAR) for a segment throughout a bending motion. The purpose of this study was to simulate a pure moment protocol using a programmable spine robot, and use the data gathered to calculate the IAR for harvested specimen and those implanted with a constrained total disc replacement …

Organophosphorus Pesticides Decrease M2 Muscarinic Receptor Function In Guinea Pig Airway Nerves Via Indirect Mechanisms, Becky J. Proskocil, Donald A. Bruun, Charles M. Thompson, Allison D. Fryer, Pamela J. Lein

Biomedical and Pharmaceutical Sciences Faculty Publications

Background: Epidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE) inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on …

Implementation Of An Anthropomorphic Phantom For The Evaluation Of Proton Therapy Treatment Procedures, Ryan L. Grant

Dissertations and Theses (Open Access)

With an increasing number of institutions offering proton therapy, the number of multi-institutional clinical trials involving proton therapy will also increase in the coming years. The Radiological Physics Center monitors sites involved in clinical trials through the use of site visits and remote auditing with thermoluminescent dosimeters (TLD) and mailable anthropomorphic phantoms. Currently, there are no heterogeneous phantoms that have been commissioned to evaluate proton therapy. It was hypothesized that an anthropomorphic pelvis phantom can be designed to audit treatment procedures (patient simulation, treatment planning and treatment delivery) at proton facilities to confirm agreement between the measured dose and calculated …

Xenobiotic Metabolism Genes And Clubfoot, Amy M. Sommer

Dissertations and Theses (Open Access)

Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities of the ankle and foot. Correction of clubfoot involves months of serial manipulations, castings and bracing, with surgical correction needed in forty percent of cases. Multifactorial etiology has been suggested in numerous studies with both environmental and genetic factors playing an etiologic role. Maternal smoking during pregnancy is the only common environmental factor that has consistently been shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot and maternal smoking increases …

Robotic Simulation Of Disc Arthroplasty Surgery: Influence Of Surgical Placement On Motion Segment Dynamics, Braham K. Dhillon

Theses and Dissertations (ETD)

A variety of total disc replacement (TDR) designs exist for the treatment of disc pathologies. A key design parameter for a constrained ball and socket device is the location of the fixed center of rotation (COR). A previous study demonstrated that intact motion segment unit (MSU) mechanics and range of motion (ROM) were sensitive to the location of a prescribed sagittal plane rotational axis. Mal-alignment between the implant COR and the COR of the MSU may lead to an overloaded or over constrained condition.

Two paradigms exist for the placement of a fixed COR TDR device relative to MSU anatomy: …

Characterizing Purkinje Cell Responses And Cerebellar Influence On Fluid Licking In The Mouse, Jeri Lonece Bryant

Theses and Dissertations (ETD)

Rodents consume water by performing stereotypical, rhythmic licking movements which are believed to be driven by central pattern generating circuits located in the brainstem. Temporal aspects of rhythmic licking behavior have been shown to be represented in the olivo-cerebellar system in the form of population complex spike activity. These findings suggest that the olivo-cerebellar system is involved in the generating circuitry responsible for licking rhythm in rodents. However, the representation of licking in the simple spike activity of Purkinje cells and the consequences of loss of cerebellar function on licking behavior has not been quantified. I investigated the influence of …

Tetrahydroisoquinoline Neurotoxins In Parkinson Disease, Michael G. Decuypere

Theses and Dissertations (ETD)

The goal of this dissertation work was to (1) determine the distribution of several tetrahydroisoquinoline (TIQ) derivatives in rodent, normal human and Parkinson disease (PD) brain, (2) quantify the levels of these TIQ derivatives in common food sources in an effort to link specific food intake patterns with the development of PD and (3) examine the neurotoxicity of select TIQ derivatives in human dopaminergic cell culture. The TIQs are a family of monoamine alkaloids that share structural homology with 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP), can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell …

Measurement Of The Vascular Input Function In Mice For Dce-Mri, Dustin K. Ragan

Dissertations and Theses (Open Access)

DCE-MRI is an important technique in the study of small animal cancer models because its sensitivity to vascular changes opens the possibility of quantitative assessment of early therapeutic response. However, extraction of physiologically descriptive parameters from DCE-MRI data relies upon measurement of the vascular input function (VIF), which represents the contrast agent concentration time course in the blood plasma. This is difficult in small animal models due to artifacts associated with partial volume, inflow enhancement, and the limited temporal resolution achievable with MR imaging. In this work, the development of a suite of techniques for high temporal resolution, artifact resistant …

Thoracic Radiotherapy Treatment Planning With Cine Pet/Ct, Adam C. Riegel

Dissertations and Theses (Open Access)

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target …

An Assessment Of Obesity And Hyperphagia In Individuals With Smith-Magenis Syndrome, Carrie A. Crain

Dissertations and Theses (Open Access)

Smith-Magenis syndrome (SMS;OMIM# 182290) is a multiple congenital anomalies and mental retardation syndrome caused by a 3.7- Mb deletion on chromosome 17p11.2 or a mutation in the RAI1 gene. Although the majority of the SMS phenotype has been well described, limited studies are available describing growth patterns in SMS. There is some evidence that individuals with SMS develop obesity. Thus, this study aims to characterize the growth and potential influence of hyperphagia in a cohort of individuals with SMS. A retrospective chart review was conducted of 78 individuals with SMS through Baylor College of Medicine (BCM) at Texas Children¡¯s Hospital …

Systems Biology Approach To Identifying Host Interactive Pathways Modulating The Severity Of Streptococcal Sepsis, Nourtan Fatthy Abdeltawab

Theses and Dissertations (ETD)

Clinical outcomes of infectious diseases are controlled by complex interactions between the host and the pathogen. Epidemiological, genetic and molecular studies in my mentor’s laboratory provided evidence that in invasive Group A streptococcal (GAS) infections, genetic variations in both bacteria and patients influenced the severity of GAS sepsis. Allelic variations in class II human leukocyte antigens (HLA) contributed significantly to differences in the severity of group A streptococcal sepsis caused by the same virulent strain of the bacteria. HLA class II molecules present streptococcal superantigens (SAgs) to T cells, and variations in HLA class II molecules can strongly influence SAg …

Ns1 Of H5n1 Interacts With Sap-97 In A Pdz-Dependent Manner To Disrupt Epithelial Barrier Integrity, Veronica Garcia Conoley

Theses and Dissertations (ETD)

The ability of influenza A virus to cause global pandemics has been a great concern throughout history and poses a serious health risk worldwide. Pandemic outbreaks throughout history, such as the Spanish flu of 1918, have claimed the lives of millions of people worldwide. The current outbreak of avian influenza (H5N1) that began in 1997 is still claiming lives, and therefore efforts to understand the mechanisms of pathogenesis in this highly virulent virus are of the utmost importance. According to the World Health Organization, there have been 447 reported H5N1 human cases, resulting in 263 deaths. The pathology of H5N1 …

Identification Of Loci Contributing To The Smith-Magenis Syndrome-Like Phenotype And Molecular Evaluation Of The Retinoic Acid Induced 1 Gene, Stephen Williams

Theses and Dissertations

Smith-Magenis syndrome (SMS) is a multiple congenital abnormalities intellectual disability syndrome that results from a deletion of chromosome 17p11.2 or mutation of the retinoic acid inducted one gene (RAI1). SMS is characterized by a multitude of phenotypic features including craniofacial defects, short stature, obesity, intellectual disability, self-abusive behavior, sleep disturbance and behavioral abnormalities. Interestingly, although SMS is a clearly defined syndrome with a known molecular change at its foundation, ~40% of all candidate cases sent to the Elsea lab for evaluation do not have a mutation or deletion of RAI1. We hypothesize that at least one other locus must be …

Synthesis Of An Endothelial Cell Mimicking Surface Containing Thrombomodulin And Endothelial Protein C Receptor, Karl E. Kador

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Synthetic materials for use in blood contacting applications have been studied for many years with limited success. One of the main areas of need for these materials is the design of synthetic vascular grafts for use in the hundreds of thousands of patients who have coronary artery bypass grafting, many without suitable veins for autologous grafts. The design of these grafts is constrained by two common modes of failure, the formation of intimal hyperplasia (IH) and thrombosis. IH formation has been previously linked to a mismatching of the mechanical properties of the graft and has been overcome by creating grafts …

A Toolkit For Rapid Gene Mapping In The Nematode Caenorhabditis Briggsae, Daniel C. Koboldt, Julia E. Staisch, Bavithra Thillainathan, Karen Haines, Scott Everet Baird, Helen M. Chamberlin, Eric S. Haag, Raymond D. Miller, Bhagwati P. Gupta

Biological Sciences Faculty Publications

Background

The nematode C. briggsae serves as a useful model organism for comparative analysis of developmental and behavioral processes. The amenability of C. briggsae to genetic manipulations and the availability of its genome sequence have prompted researchers to study evolutionary changes in gene function and signaling pathways. These studies rely on the availability of forward genetic tools such as mutants and mapping markers.

Results

We have computationally identified more than 30,000 polymorphisms (SNPs and indels) in C. briggsae strains AF16 and HK104. These include 1,363 SNPs that change restriction enzyme recognition sites (snip-SNPs) and 638 indels that range between 7 …

Modulation Of Cocaine-Like Behavioural Activity By Serotonin Uptake Inhibition Relative To The Effects Of The Novel And Selective Dopamine Transporter Inhibitor, D-84, Angela Batman

Theses and Dissertations

Cocaine dependence is a major health concern worldwide, but despite this high rate of abuse there are currently no approved therapies for cocaine dependence. Replacement pharmacotherapies are one possible approach for treating cocaine dependence, and identification of such therapeutics for cocaine abuse is the long-term goal of this research. Cocaine binds to, and inhibits uptake at the dopamine (DAT), serotonergic (SERT) and noradrenaline (NET) uptake transporters, but studies have shown that cocaine produces its strong behavioural and positive reinforcing effects through inhibition of the DAT. To this end a great number of diverse, non-selective DAT-inhibiting compounds have been investigated as …

Evaluating Forensic Dna Evidence, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Living On Autopilot: How Your Brain Thinks For You, Andrea Stathopoulos '10

Honor Scholar Theses

One way in which humans are set apart from other animals is by our impressive intellectual capacities. Humans are commonly considered to be true masters of rational, conscious control over our actions. However, that feeling of control may be mostly illusory. Accumulating evidence suggests that unconscious cognitive processes can account for much of human behavior. Homeostasis is a clear example of the evolutionary benefit of automation, allowing valuable energy and limited attention to be diverted elsewhere. I instead want to focus on the automaticity of more complicated behaviors, ones that are typically thought to require a large amount of cognitive …

Proceedings From The Second Annual Boonshoft School Of Medicine Medical Student Research Symposium, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Second Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 1, 2010.

Development Of A Functional Mri Olfactory Protocol, Jeremy Mangum

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many people can spend a few days with an acute form of sinusitis, a stuffy nose, or sinus congestion that inhibits their ability to smell, but there are fourteen million Americans over the age of fifty that suffer from some form of chronic olfactory dysfunction. Some neurological disorders such as Parkinson's disease and Alzheimer's disease have demonstrated that olfactory dysfunction is a frequent and early sign. While these diseases have no known cure, there are medicines that exist to slow the progression of such debilitating illnesses. By identifying such diseases in their early stages, we can improve the quality of …

Palmitoleate Attenuates Palmitate-Induced Bim And Puma Up-Regulation And Hepatocyte Lipoapoptosis., Yuko Akazawa, Sophie Cazanave, Justin L. Mott, Nafisa Elmi, Steven F. Bronk, Shigeru Kohno, Michael R. Charlton, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Saturated free fatty acids induce hepatocyte lipoapoptosis. This lipotoxicity involves an endoplasmic reticulum stress response, activation of JNK, and altered expression and function of Bcl-2 proteins. The mono-unsaturated free fatty acid palmitoleate is an adipose-derived lipokine which suppresses free fatty acid-mediated lipotoxicity by unclear mechanisms. Herein we examined the mechanisms responsible for cytoprotection.

METHODS: We employed isolated human and mouse primary hepatocytes, and the Huh-7 and Hep 3B cell lines for these studies. Cells were incubated in presence and absence of palmitate (16:0), stearate (18:0), and or palmitoleate (16:1, n-7).

RESULTS: Palmitoleate significantly reduced lipoapoptosis by palmitate …

Occipital Nerve Stimulator Systems: Review Of Complications And Surgical Techniques, Steven Falowski, Dajie Wang, Arvind Sabesan, Ashwini Sharan

Department of Neurosurgery Faculty Papers

Introduction: Stimulation of the occipital nerves is becoming more widely accepted in the treatment of occipital neuritis and migraine disorders.

Objective: Presently, equipment available for spinal cord stimulation is adapted for insertion into the subcutaneous space over the occipital nerves. Many technical factors need to be reassessed to optimize the therapy.

Methods: We performed a retrospective review of patients implanted from 2003 to 2007 at a single center. We aimed to analyze the rate of surgical complications related to implantation technique. A total of 28 patients were present for analysis. Patients were followed up to 60 months with a mean …

Impact Of Delay To Angioplasty In Patients With Acute Coronary Syndromes Undergoing Invasive Management : Analysis From The Acuity (Acute Catheterization And Urgent Intervention Triage Strategy) Trial, Paul Sorajja Md, Bernard J. Gersh Mb, Chb, Dphil, David A. Cox Md, Michael G. Mclaughlin Md, Peter Zimetbaum Md, Costantino Constantini Md, Thomas D. Stuckey Md, James E. Tcheng Md, Roxana Mehran Md, Alexandra J. Lansky Md, Cindy L. Grines Md, Gregg W. Stone Md

Department of Medicine

No abstract provided.

Role Of Flgt In Anchoring The Flagellum Of Vibrio Cholerae, Raquel M. Martinez, Brooke A. Jude, Thomas J. Kirn, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Flagellar motility has long been regarded as an important virulence factor. In Vibrio cholerae, the single polar flagellum is essential for motility as well as for proper attachment and colonization. In this study, we demonstrate that the novel flagellar protein FlgT is involved in anchoring the flagellum to the V. cholerae cell. A screen for novel colonization factors by use of TnphoA mutagenesis identified flgT. An in-frame deletion of flgT established that FlgT is required for attachment, colonization, and motility. Transmission electron microscopy revealed that while the flgT mutant is capable of assembling a phenotypically normal flagellum, …

Distribution Of Allatostatin C-Like Immunoreactivity In The Central Nervous System Of The Copepod Crustacean Calanus Finmarchicus, Caroline H. Wilson, Andrew E. Christie

Health Sciences and Kinesiology Faculty Articles

The C-type allatostatins (C-ASTs) are a family of highly pleiotropic arthropod neuropeptides. In crustaceans, transcriptomic/mass spectral studies have identified C-ASTs in the nervous systems of many species; the cellular distributions of these peptides remain unknown. Here, the distribution of C-AST was mapped in the nervous system of the copepod Calanus finmarchicus, the major contributor to the North Atlantic’s zooplanktonic biomass; C-AST-immunopositive neurons were identified in the protocerebrum, in several peripheral ganglia associated with feeding appendages, and in the ganglia controlling the swimming legs, with immunopositive axons present throughout the ventral nerve cord. In addition, axons innervating the dorsal longitudinal …