Medical Sciences Commons^™

Effect Of Chronic Airway Inflammation Induced By Allergen Sensitization On Vagal Bronchopulmonary Sensory Nerves In Rats, Guangfan Zhang

University of Kentucky Doctoral Dissertations

Airway hyperresponsivness (AHR) is one of most prominent pathophysiological features of asthma. Increasing evidence suggests that vagal bronchopulmonary afferents may be involved in the development of AHR. However, the underlying mechanisms are not clear. Therefore, the purpose of this dissertation was to investigate the effect of chronic airway inflammation induced by allergen sensitization on vagal bronchopulmonary afferents. The study was carried out in an animal model of allergic asthma. Brown-Norway rats were sensitized by intraperitoneal Ovalbumin (Ova) and exposed to aerosolized Ova 3 times/week for three weeks. Control rats received the vehicle. In vivo single-fiber recording technique was applied in …

Reduced Acute Inflammatory Responses To Microgel Conformal Coatings, Amanda W. Bridges, Neetu Singh, Kellie L. Burns, Julia E. Babensee, L. Andrew Lyon, Andrés J. García

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Implantation of synthetic materials into the body elicits inflammatory host responses that limit medical device integration and biological performance. This inflammatory cascade involves protein adsorption, leukocyte recruitment and activation, cytokine release, and fibrous encapsulation of the implant. We present a coating strategy based on thin films of poly(N-isopropylacrylamide) hydrogel microparticles (i.e. microgels) cross-linked with poly(ethylene glycol) diacrylate. These particles were grafted onto a clinically relevant polymeric material to generate conformal coatings that significantly reduced in vitro fibrinogen adsorption and primary human monocyte/macrophage adhesion and spreading. These microgel coatings also reduced leukocyte adhesion and expression of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, …

Multiple Forms Of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15., Nicholas J Wang, Alexander S Parokonny, Karen N Thatcher, Jennette Driscoll, Barbara M Malone, Naghmeh Dorrani, Marian Sigman, Janine M Lasalle, N Carolyn Schanen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15)] that has been called inverted duplication 15 or isodicentric 15 [idic(15)], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR) that are found clustered in the …

Longitudinal Association Of Sleep-Disordered Breathing And Nondipping Of Nocturnal Blood Pressure In The Wisconsin Sleep Cohort Study, Khin Mae Hla, Terry Young, Laurel Finn, Paul E. Peppard, Mariana Szklo-Coxe, Maryan Stubbs

Community & Environmental Health Faculty Publications

Study objectives: The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping.

Methods: The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by …

Dependence In Prestroke Mobility Predicts Adverse Outcomes Among Patients With Acute Ischemic Stroke, Mary I. Dallas, Shari Rone-Adams, John L. Echternach, Lawrence M. Bass, Dawn M. Bravata

Rehabilitation Sciences Faculty Publications

Background and Purpose - Stroke survivors are commonly dependent in activities of daily living; however, the relation between prestroke mobility impairment and poststroke outcomes is poorly understood. The primary objective of this study was to evaluate the association between prestroke mobility impairment and 4 poststroke outcomes. The secondary objective was to evaluate the association between prestroke mobility impairment and a plan for physical therapy.

Methods - This was a secondary analysis of the National Stroke Project data, a retrospective cohort of Medicare beneficiaries who were hospitalized with an acute ischemic stroke (1998 to 2001). Logistic-regression modeling was used to examine …

Gene Therapy Using Tet-Repressor System To Modulate Prostate Tumor Microenvironment, Nazita Yousefieh

Theses and Dissertations in Biomedical Sciences

Prostate cancer is the most commonly diagnosed malignancy in men in the United States and is projected to be the third most frequent cause of male cancer-related deaths in 2007 after lung and skin cancers. The initial treatment for prostate cancer at early stages is prostatectomy or radiation, which usually is curative. However, approximately 20% of patients are not cured by such treatments and their cancer recurs, sometimes with long latencies. In other patients prostate cancer is diagnosed only after the cancer has metastasized and there are no effective therapies at this stage. Therefore immunotherapy seems to be a promising …

Eosinophilic Fasciitis: Demographics, Disease Pattern And Response To Treatment: Report Of 12 Cases And Review Of The Literature, Lindsay Bischoff, Chris T. Derk

Department of Medicine Faculty Papers

BACKGROUND:
Eosinophilic fasciitis is a rare scleroderma-like illness. The clinical spectrum of the disease has evolved since its initial description.

METHODS:
We identified all patients diagnosed with eosinophilic fasciitis over the past 10 years at our scleroderma clinic. Demographics, disease pattern, serologies, tissue pathology and reponse to treatment were all recorded.

RESULTS:
Twelve patients with eosinophilic fasciitis were identified in our clinic over the past 10 years. The mean age at diagnosis was 49.8 +/- 9.8 years, with nine female and three male patients. The first symptoms were noticed at an average of 8.8 +/- 6.1 months before diagnosis. The …

Hiv-1 Tat Protein Alter The Tight Junction Integrity And Function Of Retinal Pigment Epithelium: An In Vitro Study., Ling Bai, Zhenping Zhang, Hui Zhang, Xiumei Li, Qiurong Yu, Haotian Lin, Wenhui Yang

Department of Medicine Faculty Papers

BACKGROUND: How HIV-1 enter into the eyes remains obscure. We postulated that HIV-1 Tat protein can alter the expression of specific tight-junction proteins and disturb the blood retinal barrier, and contributes to HIV trafficking into the eyes. This study is to determine the effects of HIV-1 Tat proteins on the barrier function and tight-junction protein expression of retinal pigment epithelial cell (RPE). METHODS: A human RPE cell line (D407) cultured on microporous filter-supports was used. After treating with HIV-1 Tat protein, transepithelial electrical resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells …

The Notch Signaling Pathway Drives Astrogliogenesis By Regulating The Expression Of The Transcription Factors Nfia And Sox9, Derek Janssens, Merritt Taylor

Student Summer Scholars Manuscripts

In the developing nervous system the Notch signaling pathway has recently been shown to be necessary and sufficient for neural stem cells to differentiate into astroctyes, a process called astrogliogenesis. However, the mechanism of how Notch signaling regulates this process has not yet been characterized. Our lab is examining whether Notch signaling controls the expression of the genes NFIA and Sox9 which are known to regulate astogliogenesis. These candidate genes were selected because their DNA sequences have characteristics that indicate their expression could be controlled by Notch through a transcriptional complex of Notch and other proteins, including the DNA binding …

Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe

Theses and Dissertations

Genetic deletion or pharmacological blockade of the CB1 receptor has been reported to impair extinction learning in aversive conditioning (i.e., conditioned fear and Morris water maze) paradigms, but not in operant procedures in which food reinforcement is earned. It is difficult to discern whether the differential effects caused by CB1 receptor disruption on extinction result from the hedonics (i.e., aversive vs. appetitive) or is related to the required responses associated with these disparate tasks. In order to evaluate whether the hedonics is the determining factor, we used either aversive (i.e., escape from bright lights and air turbulence) or appetitive (i.e., …

Role Of The Reactive Oxygen Species Peroxynitrite In Traumatic Brain Injury, Ying Deng

University of Kentucky Doctoral Dissertations

Reactive oxygen species (ROS) is cytotoxic to the cell and is known to contribute to secondary cell death following primary traumatic brain injury (TBI). We described in our study that PN is the main mediator for both lipid peroxidation and protein nitration, and occurred almost immediately after injury. As a downstream factor to oxidative damage, the peak of Ca2+-dependent, calpainmediated cytoskeletal proteolysis preceded that of neurodegeneration, suggesting that calpain-mediated proteolysis is the common pathway leading to neuronal cell death. The time course study clearly elucidated the interrelationship of these cellular changes following TBI, provided window of opportunity for pharmacological intervention. …

United States Regulation Of Stem Cell Research: Recasting Government's Role And Questions To Be Resolved, Owen C. B. Hughes, Alan L. Jakimo, Michael J. Malinowski

Journal Articles

This article directly addresses the stem cell controversy, but also the broader history and norms regarding the roles of federal and state government in U.S. science research funding.

Tissue Engineering The Motoneuron To Muscle Segment Of The Stretch Reflex Arc Circuit Utilizing Micro-Fabrication, Interface Design And Defined Medium Formulation, Mainak Das

Electronic Theses and Dissertations

The stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its original length so as to prevent any kind of injury. It performs this compensation process using a simple negative feed back circuit called …

The Effect Of Pparγ Activation By Pioglitazone On The Lipopolysaccharide-Induced Pge2 And No Production: Potentialunderlying Alteration Of Signaling Transduction, Bin Xing

University of Kentucky Doctoral Dissertations

Microglia-mediated neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Uncontrolled microglia activation produces major proinflammatory factors including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) that may cause dopaminergic neurodegeneration. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone has potent antiinflammatory property. We hypothesize pioglitazone protects dopaminergic neuron from lipopolysaccharide (LPS)-induced neurotoxicity by interacting with relevant signal pathways, inhibiting microglial activation and decreasing inflammatory mediators.

First, the neuroprotection of pioglitazone was explored. Second, the signaling transductions such as jun N-terminal kinase (JNK) and the interference with these pathways by pioglitazone were investigated. Third, the effect of …

Endothelial Cell Dysfunction By Environmental Contaminants, Elizabeth Grace Oesterling

University of Kentucky Doctoral Dissertations

Within the last few decades, epidemiological evidence has linked exposure to air pollution, both its particles and its organic components, with cardiovascular disease (CVD) progression. CVD is a life long disease with the disruption of the endothelium being the inaugural event in this inflammatory process. The vascular endothelium is extremely susceptible to environmental insults given its tremendous surface area and that it is in constant contact with blood and components circulating within the blood, including xenobiotics. The endothelium is important as a barrier from blood constituents however, dysfunction of this barrier leads to the influx of lymphocytes and granulocytes that …

Translational Regulatory Mechanisms Of The Rat And Human Multidrug Resistance Protein 2, Yuanyuan Zhang

University of Kentucky Doctoral Dissertations

Multidrug resistance protein 2 (MRP2) is the second member the C subfamily in the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) efflux transporters. MRP2 is a critical player for generation of bile acidindependent bile flow and biliary excretion of glutathione, glucuronate and sulfate conjugates of endo- and xenobiotics. Dysfunctional expression of MRP2 is associated with Dubin-Johnson Syndrome.

Pathological and physiological states or xenobiotics change the MRP2 expression level. Under some conditions, expression of the human MRP2 and rat Mrp2 proteins are regulated at the translation level. There are several transcription initiation sites in MRP2/Mrp2 gene. The 5’ untranslated regions (5’UTRs) …

Genetic Regulation Of Hematopoietic Stem Cell Aging, Erin J. Oakley

University of Kentucky Doctoral Dissertations

It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. In C57BL/6 (B6) mice, the HSC population steadily increases with age, whereas in DBA/2 (D2) mice, this population declines. Our lab has previously mapped a quantitative trait locus (QTL) to murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In these dissertation studies, I first aim to …

Regulation Of L-Type Voltage-Dependnet Calcium Channels By The Rem Gtpase, Chunyan Pang

University of Kentucky Doctoral Dissertations

The Rem, Rem2, Rad, and Gem/Kir GTPases, comprise a novel subfamily of the small Ras-related GTP-binding proteins known as the RGK GTPases, and have been shown to function as potent negative regulators of high voltage-activated (HVA) Ca²⁺ channels upon overexpression. HVA Ca²⁺ channels modulate Ca²⁺ influx in response to membrane depolarization to regulate a wide variety of cellular functions and they minimally consist of a pore-forming α1 subunit, an intracellular β subunit, and a transmembrane complex α₂/δ subunit. While the mechanisms underlying RGK-mediated Ca²⁺ channel regulation remain poorly defined, it appears that both membrane …

Elucidating A Normal Function Of Huntingtin By Functional And Microarray Analysis Of Huntingtin-Null Mouse Embryonic Fibroblasts., Hua Zhang, Sudipto Das, Quan-Zhen Li, Ioannis Dragatsis, Joyce Repa, Scott Zeitlin, György Hajnóczky, Ilya Bezprozvanny

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The polyglutamine expansion in huntingtin (Htt) protein is a cause of Huntington's disease (HD). Htt is an essential gene as deletion of the mouse Htt gene homolog (Hdh) is embryonic lethal in mice. Therefore, in addition to elucidating the mechanisms responsible for polyQ-mediated pathology, it is also important to understand the normal function of Htt protein for both basic biology and for HD. RESULTS: To systematically search for a mouse Htt function, we took advantage of the Hdh +/- and Hdh-floxed mice and generated four mouse embryonic fibroblast (MEF) cells lines which contain a single copy of the Hdh …

Proteomic Profiling Of Endorepellin Angiostatic Activity On Human Endothelial Cells., Jason J Zoeller, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Endorepellin, the C-terminal domain V of the heparan sulfate proteoglycan perlecan, exhibits powerful and targeted anti-angiogenic activity on endothelial cells. To identify proteins involved with endorepellin anti-angiogenic action, we performed an extensive comparative proteomic analysis between vehicle- and endorepellin-treated human endothelial cells. RESULTS: Proteomic analysis of endorepellin influence on human umbilical vein endothelial cells identified five differentially expressed proteins, three of which (beta-actin, calreticulin, and chaperonin/Hsp60) were down-regulated and two of which (vimentin and the beta subunit of prolyl 4-hydroxylase also known as protein disulfide isomerase) were up-regulated in response to endorepellin treatment-and associated with a fold change (endorepellin/control) …

Transcriptional Regulatory Network Analysis During Epithelial-Mesenchymal Transformation Of Retinal Pigment Epithelium., Craig H Pratt, Rajanikanth Vadigepalli, Praveen Chakravarthula, Gregory E Gonye, Nancy J Philp, Gerald B Grunwald

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

PURPOSE: Phenotypic transformation of retinal pigment epithelial (RPE) cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this likely involves changes in RPE cell gene expression under the control of specific transcription factors (TFs). Thus, the purpose of the present study was to identify TFs that may play a role in this process.

METHODS: Regulatory regions of genes that are differentially regulated during …

The Mechanism Of Silver Dissolution For Biomedical Devices And Hygienic Coating Applications., Yanmei Ma

Doctoral

This work focuses on the mechanism of silver dissolution for biomedical and hygienic coating applications. The research work began from the investigation of silver dissolution behaviour from pure silver and silver-platinum alloys in solutions with or without chloride using the technique of cyclic volammetry (CV). A zero resistance amperometry (ZRA) measurement was carried out to study the effect of platinum on the silver dissolution behaviour in 0.89%wt. NaCI solution. The mechanism of silver dissolution from pure silver and silver-platinum alloys in 0.89%wt. NaCI solution was proposed by an equivalent circuit model under the investigation of electrochemical impedance spectroscopy (EIS). It …

Are Lymphoblastoid Cell Lines Suitable To Study Increased Smn Gene Expression By Histone Deacetylase Inhibitors?, Di̇dem Dayangaç Erden, Haluk Topaloğlu, Hayat Erdem Yurter

Turkish Journal of Medical Sciences

Aim: In this preliminary study, we aimed to analyze the effect of sodium butyrate (NB) and phenylbutyrate (PB), belonging to the class of histone deacetylase (HDAC) inhibitors, on lymphoblastoid cell lines established from spinal muscular atrophy (SMA) patients. Materials and Methods: Lymphoblastoid cell lines were established from one type I and two type III SMA patients. Following treatment of the cell lines by HDAC inhibitors, the levels of survival motor neuron 2 (SMN2) gene full length (fl-SMN2) transcripts were assessed by both standard and real time RT-PCR. To determine the levels of SMN protein, Western blot analysis was performed. Results: …

Highly Elevated Adenosine Deaminase Level In Brucellar Pleural Effusion, Mustafa Kasim Karahocagi̇l, Hayretti̇n Akdeni̇z, Azi̇z Dursun Kirikçi, Hasan Karsen, Bünyami̇n Sertoğullari

Turkish Journal of Medical Sciences

Pleural involvement is a rare presentation of brucellosis. There are only a few case reports in the literature presenting with pleural involvement due to brucellosis. In this report, we present a case with exudative pleural fluid first considered as tuberculous pleurisy due to lymphocyte predominance and elevated level of pleural adenosine deaminase, but later diagnosed as brucella pleurisy with positive serologic and microbiologic test results. In conclusion, in the differential diagnosis of pleurisies, routine serologic and bacteriologic methods appear to be more important than pleural adenosine deaminase elevation, especially in regions endemic for both tuberculosis and brucellosis.

A Personal Ethics Responsibility Example: The Relationship Between Child Development And Drugs Taken By Pregnant Mother, Çağatay Üstün, Özge Özgürler

Turkish Journal of Medical Sciences

Personal responsibility is an important ethical concept. The pregnant mother should regard this concept as of prime importance. The pregnant mother should take some precautions in order to protect her own health and that of her baby in order to provide for its normal development. In this communication, we address the general effects of medications or drugs ingested by a pregnant mother on the baby. Thus, we target refinement of the personal ethic responsibility of the mothers.

The Effects Of Intravenous Glutamine On Bacterial Translocation And Intestinal Morphology In Experimental Pancreatitis, Hüseyi̇n Berkem, Bülent C. Yüksel, Ruki̇ye Berkem, S. Yi̇ği̇t Yildiz, Kubi̇lay Gündoğdu, İ. Hakan Özel, Serdar Topaloğlu, Süleyman Hengi̇rmen

Turkish Journal of Medical Sciences

Aim: The aim of this study was to investigate the effects of intravenous glutamine administration on bacterial translocation and intestinal morphology in rats with induced acute pancreatitis. Materials and Methods: Forty-eight Wistar-Albino rats were divided into four groups (n = 12 for each group). Pancreatitis was induced with ligation of the main pancreatobiliary duct except in the sham group, in which only periportal dissection was performed. Rats in the sham and control groups were exposed to standard rat pellet. Total parenteral nutrition (TPN) was administered solely to the pancreatitis + TPN group and together with glutamine (Gln) to the pancreatitis …

Serum Homocysteine Levels In Highway Toll Collectors And The Relationship With Intima-Media Thickness Of The Carotid Artery, Ramazan Memi̇şoğullari, Beşi̇r Erdoğmuş, Hami̇t Hakan Alp, Cahi̇t Bi̇lgi̇n, Peri̇ Meram Arbak, Özlem Yavuz

Turkish Journal of Medical Sciences

Aim: A relationship between air pollution and increased intima-media thickness (IMT) has been recently reported, but its etiology is not yet well understood. We aimed to determine whether exposure to exhaust particles, which are important air pollutants, is associated with increased serum homocysteine (Hcy) levels and whether elevated Hcy levels are associated with increased IMT. Materials and Methods: Serum Hcy levels were measured by fluorometric high performance liquid chromatography in 65 male highway toll collectors (HTCs) and 43 healthy male volunteers. IMT was measured with Doppler sonography by an experienced radiologist. Results: Serum Hcy levels (14.5 ± 4.9 mmol/L, P < 0.005) and IMT (0.757 ± 0.18 mm, P < 0.001) were higher in the HTC group than in controls (12.0 ± 2.8 mmol/L and 0.612 ± 0.11 mm, respectively). A positive correlation was found between Hcy level and IMT both in the HTC group (r = 0.36; P < 0.005) and in the control group (r = 0.36; P < 0.05). Conclusions: Exposure to exhaust particles may cause an increase in oxidative stress because of an increase in serum Hcy levels, which consequently may lead to an increase in IMT. Nevertheless, further studies on the subject are needed before drawing a firm conclusion.

The Effect Of Isoflavones On Bone Mass And Bone Remodelling Markers In Postmenopausal Women, Ni̇lgün Öztürk Turhan, Fatma Bolkan, Candan İltemi̇r Duvan, Yasemi̇n Ardiçoğlu

Turkish Journal of Medical Sciences

Aim: Recently, isoflavones have attracted attention for their potential roles in the prevention and treatment of estrogen-related osteoporosis. However, the optimal dosage and the components responsible for the favorable effects of isoflavones on bone in humans are still unclear. This study aims to investigate the effect of low-dose isoflavones on bone mineral density (BMD) and on biochemical markers of bone turnover in early postmenopausal women. Materials and Methods: Ninety participants between 42-59 years of age were randomly assigned to receive twice a day either isoflavone tablet (n:45) that provided 29.8 mg genistein, 7.8 mg daidzein, and 2.4 mg glycitein per …

Is Ghrelin A Natural Anti-Microbial Agent?, Süleyman Aydin, Hi̇kmet Geçki̇l, Nermi̇n Kiliç, Fazi̇let Erman, S. Sirri Kiliç, Özfer Yeşi̇lada

Turkish Journal of Medical Sciences

No abstract provided.

What Influences Herbal Medicine Use? - Prevalence And Related Factors, Serpi̇l Aydin, Ayfer O. Bozkaya, Mümtaz M. Mazicioğlu, Ayfer Gemalmaz, Ali̇s Özçakir, Ahmet Öztürk

Turkish Journal of Medical Sciences

Aims: The use and cost of complementary/alternative medicine (CAM) has been gaining in importance worldwide. Herbal medicine is one of the most commonly used methods. To understand the effectiveness, reliability, and quality of CAM and provide standardization in its analysis, its prevalence and the factors influencing its use must be identified. This study was conducted to identify the prevalence of CAM use and the effective factors in our population. Materials and Methods: A stratified multistage probability sampling design was used in this cross-sectional, population-based study, which was conducted in Aydin. Participants were interviewed face to face by trained interviewers with …