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Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

Development And Validation Of A Measurement Scale To Analyze The Environment For Evidence-Based Medicine Learning And Practice By Medical Residents, Fangqiong Mi

Wayne State University Dissertations

A growing number of residency programs are instituting curricula to include the component of evidence-based medicine (EBM) principles and process. However, these curricula may not be able to achieve the optimal learning outcomes, perhaps because various contextual factors are often overlooked when EBM training is being designed, developed, and implemented. The purpose of the study was to develop and validate an instrument, the EBM Environment Scale, to analyze the environment for EBM learning and practice as perceived by medical residents.

The development of the EBM Environment Scale underwent the process of content domain identification, item generation, review by content experts …

Autoimmunity In Transfusion Babesiosis: A Spectrum Of Clinical Presentations., Jay H Herman, Saleh Ayache, Danuta Olkowska

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transfusion-acquired babesiosis can be an asymptomatic or self-limited febrile hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant course with the development of life-threatening complications may be seen in immunocompromised or splenectomized patients. As in malaria, erythrocyte parasitemia is often associated with nonimmune hemolysis, and can be treated with erythrocytapheresis. Just as warm autoantibodies have been reported in malaria infection, the development of autoantibody-mediated immune hemolysis has been reported in babesiosis. We treated a previously healthy male with multiple injuries from a motor vehicle accident necessitating massive transfusion. Late in the hospitalization, his blood smear revealed Babesia microti, …

Recent Advances On Skin-Resident Stem/Progenitor Cell Functions In Skin Regeneration, Aging And Cancers And Novel Anti-Aging And Cancer Therapies., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging …

Characterization And Optimization Of Microelectrode Arrays For Glutamate Measurements In The Rat Hippocampus, Pooja Mahendra Talauliker

University of Kentucky Doctoral Dissertations

An overarching goal of the Gerhardt laboratory is the development of an implantable neural device that allows for long-term glutamate recordings in the hippocampus. Proper L-glutamate regulation is essential for hippocampal function, while glutamate dysregulation is implicated in many neurodegenerative diseases. Direct evidence for subregional glutamate regulation is lacking in previous in vivo studies because of limitations in the spatio-temporal resolution of conventional experimental techniques. We used novel enzyme-coated microelectrode arrays (MEAs) for rapid measurements (2Hz) of extracellular glutamate in urethane-anesthetized rats. Potassium-evoked glutamate release was highest in the cornu ammonis 1 (CA1) subregion and lowest in the cornu ammonis …

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

Induction Of Interferon And Interferon Signaling Pathways By Replication Of Defective Interfering Particle Rna In Cells Constitutively Expressing Vesicular Stomatitis Virus Replication Proteins, Debasis Panda, Phat X. Dinh, Lalit Beura, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

We show here that replication of defective interfering (DI) particle RNA in HEK293 cells stably expressing vesicular stomatitis virus (VSV) replication proteins potently activates interferon (IFN) and IFN signaling pathways through upregulation of IFN- promoter, IFN-stimulated response element (ISRE) promoter, and NF-κB promoter activities. Replication of DI particle RNA, not mere expression of the viral replication proteins, was found to be critical for induction of IFN and IFN signaling. The stable cells supporting replication of DI RNA described in this report will be useful in further examining the innate immune signaling pathways and the host cell functions in viral genome …

Towards An Understanding Of The Herpes Simplex Virus Type 1 Latency-Reactivation Cycle, Guey-Chuen Perng, Clinton Jones

School of Veterinary and Biomedical Sciences: Faculty Publications

Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A …

Method For Identification Of Virulence Determinants, Raul G. Barletta, Beth Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Disclosed are methods for the determination of virulence determinants in bacteria and in particular bacteria of the genus Mycobacterium. Also disclosed are compositions and methods for stimulating an immune response in an animal using bacteria and virulence determinants identified by the methods of the present invention.

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Is Oxidative Stress An Etiologic Factor In Idiopathic Male Infertility?, Ercan Yeni̇, Hali̇l Çi̇ftçi̇, Murat Savaş, Ayhan Veri̇t, Abdullah Taşkin

Turkish Journal of Medical Sciences

The total antioxidant capacity (TAC) and total peroxide (TP) levels in the blood and seminal plasma of idiopathic infertile patients were compared with those of fertile controls to determine the role of oxidative stress in the etiology of idiopathic male infertility. Material and methods: Thirty-two idiopathic infertile males and 30 healthy, married, age-matched control subjects were included in the study. TAC and TP levels were measured in the blood and seminal plasma, and sperm parameters were studied in both groups. Results: Sperm parameters were significantly impaired in the study group compared with the controls. Blood plasma TAC and TP levels …

The Effects Of Adding Methylprednisolone To Low-Potassium Dextran Solution On Preserved Ischemic Lungs, Ali̇ Yegi̇nsu, Makbule Ergi̇n, Hüseyi̇n Özyurt, Çi̇ğdem Elmas, Güleser Çağlar Göktaş

Turkish Journal of Medical Sciences

To investigate the effects of adding methylprednisolone to low-potassium dextran solution on cold-preserved ischemic lungs. Materials and methods: The study included 42 rat lung blocks that were divided into 7 groups (n = 6). Lung blocks were preserved in 40 mL of cold Perfadex solution, to which 5, 15, 30, 60, and 120 mg kg-1 (approximately 40, 120, 240, 480, and 960 mg L-1) of methylprednisolone were added. After a 24-h preservation period, the lungs were removed from the solution and examined. Results: As compared to the Perfadex only group, cell death and degeneration were significantly higher in the Perfadex …

Effect Of L-Carnitine On Diabetic Neuropathy And Ventricular Dispersion In Patients With Diabetes Mellitus, Hizir Ulvi̇, Recep Aygül, Recep Demi̇r

Turkish Journal of Medical Sciences

Diabetes is a common cause of polyneuropathy. Cardiac arrhythmias and markedly increased mortality rate have been demonstrated in patients with diabetic neuropathy and also demonstrated that abnormally prolonged QT dispersion interval (QTd) is associated with a higher risk of ventricular arrhythmias and sudden death. We investigated the efficacy and tolerability of L-carnitine (LC) in the treatment of diabetic neuropathy and ventricular dispersion, mainly by evaluating the effects of treatment on electrophysiological parameters. Materials and methods: We recruited 30 patients with type I or type II diabetes (mean age: 60 ± 9 years, range: 36-75; 18 males, 12 females) meeting clinical …

Effect Of Telmisartan On Vascular Endothelium In Hypertensive And Type 2 Diabetic Hypertensive Patients, Burcu Barutçuoğlu, Zuhal Parildar, M. Işil Mutaf, Di̇lek Özmen, Emi̇n Ali̇oğlu, Sara Habi̇f, Oya Bayindir

Turkish Journal of Medical Sciences

Hypertension and type 2 diabetes mellitus (DM) cause endothelial dysfunction and may result in cardiovascular disease. The aim of this study was to assess endothelial dysfunction in essential hypertensives, and normotensive and hypertensive type 2 diabetics and to evaluate the effect of telmisartan on endothelium in hypertensives. Materials and methods: Eighteen essential hypertensives (group 1), 16 type 2 diabetic hypertensives (group 2), 10 type 2 diabetic normotensives (group 3), and 10 control subjects (group 4) were included in this study. Groups 1 and 2 received 40 mg/day telmisartan for 12 weeks and were evaluated at the beginning and end. Groups …

Cervical Spine Movement During Intubation Using The Airtraq® And Direct Laryngoscopy, İ. Aydin Erden, A. Gülsün Pamuk, Şennur Uzun, Serdar Geyi̇k, Saruhan Çeki̇rge, Ülkü Aypar

Turkish Journal of Medical Sciences

To compare 2 endotracheal intubation techniques, namely direct laryngoscopy and Airtraq®, according to their influence on cervical spine movement and intubation time and success rates, complications, and hemodynamic responses. Materials and methods: Thirty three patients without cervical spine problems were enrolled in the study. Patients were randomized into direct laryngoscopy and Airtraq® groups. Assessment of movement of the cervical spine was made by taking 3 lateral cervical spine X-rays. First, when the cervical spine was in the neutral position, second during the greatest excursion of the cervical spine, and finally, after intubation. A reference line was drawn following the dorsal …

Endometrial Parameters In Ivf And Iui Administration On Elderly Women, Nafi̇ye Yilmaz, Sevtap Kiliç, Yusuf Madendağ, İlknur Madendağ, Ayli̇n Özgün, Gülnur Özakşi̇t, Sertaç Batioğlu

Turkish Journal of Medical Sciences

There are still controversial results about the role of endometrial thickness, pattern, volume, and vascularity in endometrial receptivity. We studied the predictivity of endometrial parameters in endometrial receptivity in over-aged, normogonadotrophic unexplained infertile women. Materials and methods: In this study, 150 women with an age range of 38-42 were included. The patients were divided into 4 groups: group 1 was applied recombinant FSH and intrauterine insemination, group 2 was applied clomiphene citrate and intrauterine insemination, group 3 was applied IVF, and group 4 (control group) was composed of fertile control patients. All patients in each study group had standard initiation …

Prevalence And Risk Factors Of Restless Leg Syndrome In A Single Hemodialysis Unit, Yasemi̇n Soyoral, Hayri̇ye Sayarlioğlu, Deni̇z Tuncel, Murat Şahi̇n, Ekrem Doğan, Reha Erkoç

Turkish Journal of Medical Sciences

Restless legs syndrome (RLS) is characterized by symptoms of spontaneous, continuous leg movements associated with unpleasant paresthesias. RLS is common among dialysis patients, with a reported incidence of 6.6 to 6.8 percent. This study is an attempt to find out the prevalence of RLS in our hemodialysis patients. We compared several demographic and clinical characteristics of RLS patients identified by the International Restless Legs Syndrome Study Group (IRLSSG) criteria with those of individuals without RLS. Materials and methods: We studied 76 patients with end-stage renal disease (ESRD) on hemodialysis (34 females and 42 males, mean age: 52.28 ± 18.13, range: …

Serum Total Sialic Acid, Lipid Peroxidation, And Glutathione Reductase Levels In Patients With Rheumatoid Arthritis, Surapaneni Krishna Mohan, Vishnu Priya

Turkish Journal of Medical Sciences

The changes in the serum sialic acid levels, total lipid peroxidation products (MDA), and glutathione reductase activity were estimated in patients with rheumatoid arthritis. Serum Sialic acid is known as a parameter of inflammation. This work was undertaken to assess the potential role of sialic acid as well as oxidative stress and antioxidant status in patients with rheumatoid arthritis. Materials and methods: The levels of these parameters in serum were studied in 52 subjects with rheumatoid arthritis (study subjects) and 52 age and sex matched healthy subjects as controls. Serum total sialic acid levels were determined using the assay method …

Serum Lipid And Lipoprotein Levels, Dyslipidemia Prevalence, And The Factors That Influence These Parameters In A Turkish Population Living In The Province Of Tokat*, İlhan Çeti̇n, Beytullah Yildirim, Şemsetti̇n Şahi̇n, İdri̇s Şahi̇n, İlker Eti̇kan

Turkish Journal of Medical Sciences

To determine the mean total LDL and HDL cholesterol values and trigliseride levels as well as dyslipidemia and the factors that influence the parameters mentioned above in the population living in the province of Tokat located in the Middle Black Sea (Northeastern) region of Turkey. Materials and methods: The study was performed in 58 rural and 12 urban residential areas. The 58 rural regions were selected using a cluster sampling method. A total of 1095 subjects were selected through a random sampling method. Results: The total serum cholesterol level was 186 ± 42 mg/dL with 33.7% of the participants having …

Is The Tanner–Whitehouse (Tw3) Method Sufficiently Reliable For Forensic Age Determination Of Turkish Children?*, Bora Büken, Alp Alper Şafak, Erhan Büken, Burhan Yazici, Zerri̇n Erkol, Ömer Utku Erzengi̇n

Turkish Journal of Medical Sciences

The purpose of our study was to determine the accuracy of Tanner-Whitehouse 3 (TW3-RUS) bone age (BA) assessments for forensic age estimations of Turkish children. Materials and methods: Plain radiographs of left hands and wrists of 324 children were evaluated. Mean chronological age (CA) was compared with mean bone age (BA) according to the TW3 atlas for each sex, and differences by age group were determined. Pearson correlation coefficients and cubic regression were used to determine the differences and model the relationships between mean BA and CA. Statistical analyses were carried out using R-project. Results: The difference between the mean …

Prevalence Of Helicobacter Pylori Infection In Healthcare Workers, Maliheh Metanat, Batool Sharifi-Mood, Shahrokh Izadi

Turkish Journal of Medical Sciences

Helicobacter pylori (H. pylori) is a major factor in inflammatory and malignant diseases of the gastrointestinal tract. The epidemiologic pattern of this infection varies among developed and developing countries, and is related to the general standards of living in each region. In view of the importance of this infection and its different prevalence in different regions of Iran, as well as its long-term complications, this study was conducted to investigate the prevalence of H. pylori infection and its contributing factors in Zahedan. Materials and methods: Ninety-seven healthcare workers without digestive symptoms or a history of H. pylori eradication were randomly …

Fiber Modification Of Adenoviral Vectors For Cancer Gene Therapy, Miho Murakami

All ETDs from UAB

Cancer still remains a major public health concern despite improvements in primary prevention, early detection and advanced treatments. Cancer gene therapy using human adenovirus serotype 5 (HAdV-5) as a vector has been explored as a new therapeutic approach. HAdV-5 infection is initiated by binding to the coxsackie virus and adenovirus receptor (CAR), its primary cellular receptor. However, the levels and patterns of expression of CAR vary greatly in clinical tumor tissue samples, and the expression lev-els tend to decrease as the tumors progress. The low level expression of CAR in target cancer cells diminishes the utility of HAdV-5 as a …

The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark

All ETDs from UAB

Each year 300-500 million cases of Plasmodium falciparum malaria occur, leading to more than 1 million deaths. In high malaria transmission regions, development of immunity from severe infection requires 2-10 years of persistent parasitemia. This delay has been attributed to difficulties in the development of protective humoral responses. Indeed, anti-malarial antibody responses tend to be short-lived, and immunologic memory seems to be dysfunctional in high-transmission regions. In contrast, in the low-transmission Peruvian Amazon >60% of infections are asymptomatic, suggesting that clinical immunity occurs despite low parasite exposure. To analyze more precisely the naturally-acquired humoral responses to malarial antigens and their …

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

All ETDs from UAB

Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …

Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters

All ETDs from UAB

The ubiquitin proteasome system (UPS) is a coordinated process by which the cell can control protein distribution and abundance. Proteins are marked for turnover by the construction of a polyubiquitin chain on the protein substrate. Once engaged by the proteasome, the ubiquitin side-chain is disassembled by proteasomal deubiquitinating enzymes (DUBs), preventing entry of ubiquitin into the proteasome and recycling it for use in future reactions. One of the DUBs that resides on the proteasome is Ubiquitin Specific Protease 14 (Usp14), which is mutated in the ataxia (axJ) mice. This mutation results in pronounced physical deficits and, unexpectedly, a deficit in …

Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri

All ETDs from UAB

Acid Sensing Ion Channel 1 is one of the many proteins in the Epithelial Sodium Channel/Degenerin family. The proteins in this family interact to form cation channels with unique biophysical properties and can all be inhibited by the small molecule amiloride. Their expression in many different cell types underlies their involvement in a large variety of physiological and pathophysiological processes. ASIC-1 containing channels, specifically, are an important therapeutic target for ischemic stroke, nociception, the invasiveness of glioblastoma cells, and many other processes including anxiety and memory formation. Of the members of the ENaC/Deg family, chicken ASIC-1 is the only protein …