Medical Sciences Commons^™

Study Of Mouse Induced Pluripotent Stem Cell Transplantation Intowistar Albino Rat Cochleae After Hair Cell Damage*, Mustafa Kürşat Gökcan, Selçuk Mülazi̇moğlu, Emre Ocak, Pinar Can, Murat Çalişkan, Ömer Beşalti, Serpi̇l Di̇zbay Sak, Gülşah Kaygusuz

Turkish Journal of Medical Sciences

Background/aim: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. Materials and methods: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the …

The Association Of Papillary Thyroid Cancer With Microcalcification In Thyroidnodules With Indeterminate Cytology Based On Fine-Needle Aspiration Biopsy, İbrahim Ali̇ Özemi̇r, Bariş Bayraktar, Ender Anilir, Kivilcim Orhun, Tunç Eren, Jüli̇de Sağiroğlu, Ayşe Bahar Ceyran, Rafet Yi̇ği̇tbaşi, Orhan Ali̇moğlu

Turkish Journal of Medical Sciences

Background/aim: Microcalcifications are generally accepted as highly specific for thyroid malignancy, especially for papillary thyroid carcinoma (PTC). The aim of this study was to determine the significance of microcalcification within nodules that were classified as being of "indeterminate cytology" (IC) according to fine-needle aspiration biopsy. Materials and methods: Patients who underwent thyroidectomy between January 2010 and 2013 were included in the study. Nodules identified as "atypia/follicular lesion of undetermined significance", "follicular neoplasm/suspicious for follicular neoplasm", or "suspicious for malignancy" were categorized as IC. Patients were subcategorized depending on the presence of microcalcification (Group 1) or its absence (Group 2). The …

The Effect Of Deep Sclerectomy On Ocular Blood Flow: A 6-Month Clinical Trial, Arzu Özsoy, Murat Si̇nan Saricaoğlu, Mehtap Çavuşoğlu

Turkish Journal of Medical Sciences

Background/aim: To investigate the effect of deep sclerectomy on retrobulbar blood flow. Materials and methods: This prospective study included 20 eyes of 20 patients with open angle glaucoma. Color Doppler imaging (CDI) examinations were performed before and 2, 12, and 24 weeks after deep sclerectomy. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were measured for the ophthalmic artery (OA), central retinal artery (CRA), and temporal and nasal short posterior ciliary arteries (SPCAs) at each examination and the results were compared. Results: A significant decrease was determined in intraocular pressure (IOP) (P < 0.001) and a significant increase in ocular perfusion pressure (OPP) (P < 0.001) at all postoperative examinations. The EDV in OA increased significantly (P < 0.001), but the change in RI was not statistically significant (P = 0.67). EDV increased and RI decreased significantly in CRA and SPCA (P < 0.001). Conclusion: Deep sclerectomy decreases IOP and increases OPP significantly. Retrobulbar blood flow was seen to improve after deep sclerectomy.

Daily Surveillance With Early Warning Scores Help Predicthospital Mortality In Medical Wards, Mi̇ne Durusu Tanriöver, Burçi̇n Halaçli, Bi̇lgi̇n Sai̇t, Serpi̇l Öcal, Arzu Topeli̇

Turkish Journal of Medical Sciences

Background/aim: To analyze the potency of a modified early warning score (EWS) to help predict hospital mortality when used for surveillance in nonacute medical wards. Materials and methods: Patients in internal medicine wards were prospectively recruited. First, highest, and last scores; and mean daily score recordings and values were recorded. Nurses calculated scores for each patient upon admission and every 4 h. The last score was the score before death, discharge, or transfer to another ward. The highest scores in total and for each single parameter were used for analysis. Results: Fifty-nine percent of 182 recruited patients had recordings eligible …

Bone Mineral Density And Growth In Children With Coeliac Disease On A Gluten Free-Diet, Ceyda Tuna Kirsaçlioğlu, Zari̇fe Kuloğlu, Aydan Tanca, Nuri̇ye Özlem Küçük, Zehra Aycan, Gönül Öçal, Arzu Ensari̇, Ayhan Gazi̇ Kalayci, Nurten Gi̇rgi̇n

Turkish Journal of Medical Sciences

Background/aim: To evaluate changes in growth and bone metabolism during consumption of a gluten-free diet (GFD) in children with coeliac disease (CD). Materials and methods: Thirty-seven children with CD (mean age of 8.8 ± 4.6 years, 21 girls) were enrolled. Anthropometric measurements, bone mineral density (BMD) in lumbar 2-4 vertebrae, and serum alkaline phosphatase, calcium, and phosphorus levels at diagnosis and at follow-up were recorded. Results: The mean follow-up period was 3.5 ± 2.3 years. The BMD of patients was significantly lower than that of control subjects at the time of diagnosis but not after 1 year of the GFD. …

Faculty Publications 2015, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 890 publications.

The Mauc Gene Encodes A Versatile Signal Sequence And Redox Protein That Can Be Utilized In Native And Non-Native Protein Expression And Electron Trnasfer Systems, Brian Dow

Electronic Theses and Dissertations

The redox-active type 1 copper site of amicyanin is composed of a single copper ion that is coordinated by two histidines, a methionine, and a cysteine residue. This redox site has a potential of +265 mV at pH7.5. Over ten angstroms away from the copper site resides a tryptophan residue whose fluorescence is quenched by the copper. The effects of the tryptophan on the electron transfer (ET) properties were investigated by site-directed mutagenesis. Lessons learned about the hydrogen bonding network of amicyanin from the aforementioned study were attempted to be used as a model to increase the stability of another …

Role Of Klf8-Cxcr4 Signaling In Breast Cancer Metastasis, Debarati Mukherjee

Electronic Theses and Dissertations

Krüppel-like factor 8 (KLF8) has been strongly implicated in breast cancer metastasis. However, the underlying mechanisms remain largely unknown. In this study we report a novel signaling from KLF8 to C-X-C cytokine receptor type 4 (CXCR4) in breast cancer. Overexpression of KLF8 in MCF-10A cells induced CXCR4 expression at both mRNA and protein levels. This induction was well correlated with increased Boyden chamber migration, matrigel invasion and transendothelial migration (TEM) of the cells towards the ligand CXCL12. On the other hand, knockdown of KLF8 in MDA-MB-231 cells reduced CXCR4 expression associated with decreased cell migration, invasion and TEM towards CXCL12. …

Patterns Of Human Herpesvirus-8 Oral Shedding Among Diverse Cohorts Of Human Herpesvirus-8 Seropositive Persons, Rachel A. Bender Ignacio, Jason D. Goldman, Amalia S. Magaret, Stacy Selke, Meei-Li Huang, Soren Gantt, Christine Johnston, Warren Phipps, Joshua Schiffer, Richard Zuckerman

Dartmouth Scholarship

Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons.

Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma., Bridgette Jones, Catherine M T Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD …

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In …

An Analysis Of Plasticity In The Rat Respiratory System Following Cervical Spinal Cord Injury And The Application Of Nanotechnology To Induce Or Enhance Recovery Of Diaphragm Function, Janelle Lorien Walker

Wayne State University Dissertations

Second cervical segment spinal cord hemisection (C2Hx) results in ipsilateral hemidiaphragm paralysis. However, the intact latent crossed phrenic pathway can restore function spontaneously over time or immediately following drug administration.

WGA bound fluorochromes were administered to identify nuclei associated with diaphragm function in both the acute and chronic C2Hx models. WGA is unique in that it undergoes receptor mediated endocytosis and is transsynaptically transported across select physiologically active synapses. Comparison of labeling in the acutely injured to the chronically injured rat provided an anatomical map of spinal and supraspinal injury induced synaptic plasticity. The plasticity occurs over time in the …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Ketogenic Diet Decreases Emergency Room Visits And Hospitalizations Related To Epilepsy., Husam R. Kayyali, Anastasia Luniova, Ahmed Abdelmoity

Manuscripts, Articles, Book Chapters and Other Papers

Background. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD) on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy. Methods. This is a retrospective review of children treated with the KD in one tertiary center. We compared a 12 months' period prior to KD with 12 months after the diet was started in regard to the number of emergency department (ED) visits, hospitalizations, …

Introduction To Bioethics Special Supplement V: Ethical Issues In Genomic Testing Of Children., John D. Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Next-generation genome sequencing of children is one of the most promising and most challenging new technologies in pediatrics. On the one hand, it offers the hope that we will be able to diagnose rare conditions that were previously impossible to diagnose, which, in turn, might lead to new treatments. On the other hand, the technology for sequencing presents daunting problems of interpretation. It is problematic to conduct the research necessary to characterize the pathogenicity of those variants at the same time that we are using them to guide the clinical care of children who have complex medical problems. It is …

Whole-Genome Sequencing And Disability In The Nicu: Exploring Practical And Ethical Challenges., Michael J. Deem

Manuscripts, Articles, Book Chapters and Other Papers

Clinical whole-genome sequencing (WGS) promises to deliver faster diagnoses and lead to better management of care in the NICU. However,several disability rights advocates have expressed concern that clinical use of genetic technologies may reinforce and perpetuate stigmatization of and discrimination against disabled persons in medical and social contexts. There is growing need, then, for clinicians and bioethicists to consider how the clinical use of WGS in the newborn period might exacerbate such harms to persons with disabilities. This article explores ways to extend these concerns to clinical WGS in neonatal care. By considering these perspectives during the early phases of …

The Level Of Nmda Receptor In The Membrane Modulates Amyloid-Β Association And Perforation, Christian Peters, Fernando J. Sepúlveda, Eduardo Fernández-Pérez, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

Alzheimer’s disease is a neurodegenerative disorder that affects mostly the elderly. The main histopathological markers are the senile plaques formed by amyloid-β peptide (Aβ) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. Several membrane proteins and lipids interact with Aβ affecting its toxicity in neurons. Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by Aβ on the plasma membrane. In fact, our results showed that decreasing NMDARs, using enzymatic or siRNA …

Structural Basis For Lipid-And Calmodulin-Mediated Akt Activation In Breast Cancer Cells, Constance Agamasu

All ETDs from UAB

Growth and survival signals initiated at the cell surface by receptor-ligand interactions often involve a downstream activation of Akt, a serine/threonine kinase critical in regulating cell survival, apoptosis and oncogenesis. Hyper-activation of Akt is a common tumorigenic event, thereby making the Akt activation pathway a prime target for cancer therapy. The translocation of Akt to the plasma membrane (PM) for phosphorylation is a critical step in the Akt activation pathway. It has been established that membrane binding of Akt is mediated by direct interactions between its pleckstrin homology domain (PHD) and membrane lipid phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]. There is now emerging …

Role Of Autocrine And Paracrine Wnt Signaling In Chronic Myeloid Leukemia Stem Cells, Puneet Agarwal

All ETDs from UAB

Treatment of chronic myeloid leukemia (CML) with BCR-ABL tyrosine kinase inhibitors (TKIs) fails to eradicate the leukemia stem cells (LSCs) from which the disease arises. Previously, we and others have shown that LSC persistence is related to kinase-independent mechanisms and mediated in part by signals from the bone marrow microenvironment (BMM). Specifically, we found that WNT signaling from the BMM may contribute to preservation of CML LSC following TKI treatment. Wnt secretion and activity requires their palmitoylation by the Porcupine acyltransferase (PORCN). WNT974 (formerly LGK974) is a potent PORCN inhibitor that blocks WNT signaling and demonstrates in vivo efficacy against …

Mechanisms Of Innate And Adaptive Immune Function In Parkinson Disease, Heather Elizabeth Allen

All ETDs from UAB

Parkinson disease (PD) is a common neurodegenerative movement disorder characterized pathologically by loss of dopaminergic neurons in the substantia nigra and aggregation of alpha-synuclein (α-syn) into large inclusions. The association of mutations and gene multiplications in SNCA, the gene encoding α-syn, with rare familial forms of PD led to the discovery that α-syn plays a key role in the pathogenesis of PD. The mechanism by which α-syn mediates its toxicity remains uncertain. A leading hypothesis states that the toxic effects of α-syn are mediated by activation of both the innate and adaptive immune systems within the central nervous system. Supporting …

Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo

All ETDs from UAB

The diarrheal disease cholera is caused by the Gram-negative and motile bacterium Vibrio cholerae of serogroups O1 and O139. V. cholerae can switch between planktonic (motile) and sessile (biofilm) lifestyles. Biofilms are sessile communities encased in a self-produced extracellular matrix mainly composed of exopolysaccharide, proteins and extracellular DNA. Biofilm formation enhances the capacity of V. cholerae to persist in environmental waters and increases its infectivity. The bacterial second messenger cyclic diguanylic acid (c-di-GMP) regulates the transition between motile and biofilm lifestyles in V. cholerae. At low cell density, two c-di-GMP receptors, the LuxR-type regulator VpsT and the NtrC-type regulator VpsR …

The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk

All ETDs from UAB

Multiple sclerosis is the most common neurological disorder in young adults. Current treatments modulate the immune system, but no treatments prevent central nervous system damage. Inflammation occurs even during disease remission, contributing to ongoing damage and resulting in disease progression. The lack of neuroprotective treatments despite continued inflammatory onslaught in the central nervous system indicates the need for therapeutic discovery in this area. One potential therapeutic target is glutamate, whose dysregulation in multiple sclerosis has been implicated in excitotoxic cellular death. Herein we describe the roles of glutamate in multiple sclerosis and explore the blockade of a source of excitotoxic …

Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge

All ETDs from UAB

Levodopa-induced dyskinesia (LID) is a persistent behavioral sensitization that develops after repeated levodopa (L-DOPA) exposure in Parkinson disease (PD) patients. LID is characterized by a “priming effect”, whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent administrations of L-DOPA. In neurons, transcriptional regulation through dynamic changes to epigenetic modifications, including DNA methylation and histone acetylation, have been shown pivotal to many long-term behavioral modifications; however, their role in LID has been minimally explored. Using a rodent model, we show LID development leads to the aberrant expression of DNA demethylating enzymes and locus-specific changes to DNA …

Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser

All ETDs from UAB

Parkinson disease (PD) is the most common neurodegenerative movement disorder for which no treatments exist capable of slowing progression of the disease. One obstacle slowing the development of novel therapies is the lack of molecular biomarkers for PD prognosis, tracking of disease progression, and assessing efficacious target engagement of compounds that do reach clinical trials. Missense mutations in LRRK2 account for between 1-5% of late onset PD and lead to increases in LRRK2 kinase activity and LRRK2 autophosphorylation. This thesis characterizes the secretion of LRRK2 into extracellularly secreted microvesicles called exosomes. We find that kinase-active LRRK2 is secreted within exosomes …

Copper Chaperone In Streptococcus Mutans Biofilm Formation And Dispersion Of Biofilms By Small Molecules, Sandra Stephanie Garcia

All ETDs from UAB

program pilot study randomly assigned 100 women, aged 19 to 25 to two groups. One

Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover

All ETDs from UAB

Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for nearly three decades. Recently, though, growing evidence indicates that early-life SSRI exposure triggers long-lasting behavioral abnormalities. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior, reduced social behavior, and increased risk for depression in adolescence. Similarly, in rodents, perinatal SSRI exposure leads to increased traits of anxiety- and depression-like behavior. Interestingly, certain individuals are more susceptible to early-life SSRI exposure than others, suggesting that perinatal SSRI exposure poses greater risks for negative outcome within certain populations; however, …

Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham

All ETDs from UAB

Glioblastoma (GBM) is the most common and aggressive human primary malignant brain tumor with a 5-year survival rate of less than 5%. GBM is highly invasive, rendering complete surgical resection impossible. Additionally, this tumor type is relatively insensitive to radiotherapy. Thus, effective chemotherapeutic options present the last line of defense for GBM patients. Unfortunately, nearly 50% of all GBM tumors are resistant to the current chemotherapeutic standard, temozolomide (TMZ). TMZ is a DNA alkylating agent that promotes apoptosis via DNA damage. Resistance to TMZ-induced cell death is attributed to expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) resultant from …

Fcrl5 Counter-Regulates Natural And T Cell-Independent Immunoglobulin Production By Innate-Like B Cells, Eugene John Becker

All ETDs from UAB

At homeostasis and during the initial phases of primary responses to pathogens, humoral host defense is chiefly coordinated by specialized B cells known as splenic marginal zone (MZ) and body cavity-derived B-1 B cells. These front line immune mediators are termed “innate like” due to their ability to secrete broadly-reactive natural antibodies and respond rapidly to antigens in a T cell-independent manner. The production of natural antibodies possessing specificities for self-antigens allows clearance of cellular debris, maintenance of homeostasis and protection from infections that can also predispose the host to immunological disease. However, how the functions of these specialized cells …

Exploring Bacteriophage P22 As A Selective Molecular Scaffold And Molecular Sensor, Gregory Joseph Bedwell

All ETDs from UAB

The virus capsids of many dsDNA bacteriophage are finely tuned macromolecular machines. Their functionality begins at assembly, when their capsids are built under the guidance of a class of proteins referred to as scaffolding proteins. The scaffolding protein of bacteriophage P22 is a flexible, highly elongated protein that binds to the interior surface of the P22 procapsid via its C-terminal domain. The finding that N-terminus is dispensable for procapsid binding prompted the development of chimeric scaffolding protein molecules, wherein N-terminal residues of scaffold are replaced with a variety of different peptide sequences or functional proteins that are then encapsidated within …