Medicine and Health Sciences Commons^™

The Role Of Glutamate And Its Receptors In Mesocorticolimbic Dopaminergic Regions In Opioid Addiction, Yuan Guo, Hui-Ling Wang, Xiao-Hui Xiang, Yan Zhao

United States Public Health Resources

Accumulating evidence suggests that glutamate, as one of the most important excitatory neurotransmitters in the brain, plays a key role in drug addiction including opioid addiction. There is substantial evidence for glutamatergic projections into mesocorticolimbic dopaminergic neurons, which are associated with opioid psychological dependence and are also the key regions of enhancement effect. Glutamate may be involved in the process of opioid addiction not only by acting on its ionotropic and metabotropic glutamate receptors that activate several signal transduction pathways, but also by interacting with other neurotransmitters or neuropeptides such as opioids, dopamine, y-aminobutyric acid and substance P in the …

Regulation Of Alginate Production Of Pseudomonas Aeruginosa Pseudomonas Aeruginosa, Fredrick Heath Damron

Theses, Dissertations and Capstones

Pseudomonas aeruginosa (P.a.) is a major threat to the health and well being of a person living with cystic fibrosis (CF). P.a. is capable of conversion to mucoidy or alginate overproducing phenotype. Mucoidy facilitates the chronic infection of P.a. infection in the CF lung. Mutations in the anti-sigma factor mucA, result in activation of the sigma factor AlgU which promotes expression of alginate through the alginate biosynthetic operon. However, P.a. can produce alginate independent of mucA mutation via a mechanism known as regulated proteolysis. Proteases AlgW and MucP can degrade MucA to liberate and activate AlgU. In this dissertation, two …

Delayed Rejection Of Mhc Class Ii-Disparate Skin Allografts In Mice Treated With Farnesyltransferase Inhibitors, Ken Field

Faculty Journal Articles

Farnesyltransferase inhibitors (FTIs), developed as anti-cancer drugs, have the potential to modulate immune responses without causing nonspecific immune suppression. We have investigated the possibility that FTIs, by affecting T cell cytokine secretion, can attenuate alloreactive immune responses. The effects of FTIs on murine alloreactive T cells were determined both in vitro, by measuring cytokine secretion or cell proliferation in mixed lymphocyte cultures, and in vivo, by performing skin allografts from H-2^bm12mice to MHC class II-disparate B6 mice. We found that two different FTIs, ABT-100 and L-744,832, blocked secretion of IFN-γ, IL-2, IL-4, and TNF-α from naïve …

Angiotensin Ii Induction Of Regional Effects In Murine Vasculature, Albert Phillip Owens Iii

University of Kentucky Doctoral Dissertations

The renin angiotensin system (RAS) exerts many diverse physiological functions throughout the body, mediated by its effector peptide, angiotensin II (AngII). AngII has been linked with a variety of different functions ranging from the initiation of severe vascular pathologies, such as atherosclerosis and abdominal aortic aneurysm (AAA), to mundane physiological processes of fluid homeostasis, vascular contraction, and regulation of blood pressure. To provide a potential link between these functions, an in-depth analysis of regional effects of AngII on aortic vasculature was performed.

The studies presented in this dissertation tested the overall hypothesis of whether regional changes exist in the vasculature …

Regulation Of Low Density Lipoprotein Receptor Splicing Efficiency, I-Fang Ling

University of Kentucky Doctoral Dissertations

Low density lipoprotein receptor (LDLR) is an apolipoprotein E (apoE) receptor and may play a role in Alzheimer’s disease (AD) development. A single nucleotide polymorphism (SNP), rs688, that has been identified to modulate the splicing efficiency of LDLR exon 12 and is associated with higher cholesterol and AD in some case-control populations. The exon 12 deleted mRNA is predicted to produce a soluble form of LDLR that fails to mediate apoE uptake. To gain additional insights, in this study, I seek to understand the regulation of LDLR splicing efficiency. To identify functional cis-elements within LDLR exon 12, I mutated several …

Age May Be Hazardous To Outcome Following Traumatic Brain Injury: The Mitochondrial Connection, Lesley Knight Gilmer

University of Kentucky Doctoral Dissertations

Older individuals sustaining traumatic brain injury (TBI) experience a much higher incidence of morbidity and mortality. This age-related exacerbated response to neurological insult has been demonstrated experimentally in aged animals, which can serve as a model to combat this devastating clinical problem. The reasons for this worse initial response are unknown but may be related to age-related changes in mitochondrial respiration.

Evidence is shown that mitochondrial dysfunction occurs early following traumatic brain injury (TBI), persists long after the initial insult, and is severitydependent. Synaptic and extrasynaptic mitochondrial fractions display distinct respiration capacities, stressing the importance to analyze these fractions separately. …

Studies On The Role Of Acid Sphingomyelinase And Ceramide In The Regulation Of Tace Activity And Tnfα Secretion By Macrophages, Krasimira Rozenova

University of Kentucky Doctoral Dissertations

Acid Sphingomyelinase (ASMase) activity has been proposed to mediate LPS signaling in various cell types. This study shows that in macrophages, ASMase is a negative regulator of LPS-induced TNFα secretion. ASMasedeficient (asm^-/-) mice and isolated peritoneal macrophages produce several fold more TNFα than their wild-type (asm^+/+) counterparts when stimulated with LPS. The mechanism for these differences however is not transcriptional but post-translational.

The TNFα converting enzyme (TACE) catalyzes the maturation of the 26kD precursor (proTNFα) to the active 17kD form (sTNFα). In mouse peritoneal macrophages, the activity of TACE rather than the rate of TNFα mRNA …

Role Of Aryl Hydrocarbon Receptor In Chronic Inflammatory Diseases, Violeta Arsenescu

University of Kentucky Doctoral Dissertations

Aryl Hydrocarbon Receptor (AhR) is a ligand-actviated receptor known as the dioxin receptor. Environmental pollutants called dioxin-like toxicants are found in food, cigarette smoke, automobile exhaust and air. Therefore, they could chronically amplify the pathology of numerous chronic inflammatory diseases. AhR is a well known target of these environmental chemicals that disrupt endocrine signaling. By the year 2020, the number of people older than 60 years is expected to top 1 billion. The burden of treating chronic disease is significant both in dollars spent and in lost productivity. The need to identify risk factors for chronic diseases must be evaluated …

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …

Are Morphological Specializations Of The Hyolingual System In Chameleons And Salamanders Tuned To Demands On Performance?, Anthony Herrel, Stephen M. Deban, Vicky Schaerlaeken, Jean-Pierre Timmermans, D. Adriaens

Integrative Biology Faculty and Staff Publications

Extremely specialized and long tongues used for prey capture have evolved independently in plethodontid salamanders and chameleons. In both systems, the demands on tongue projection are probably similar: to maximize projection velocity and distance. Consequently, many of the design features of the projection system in these two groups have converged to an astonishing degree. Both involve the use of power amplification systems based on helically wound muscle fibers that load internal connective tissue sheets as illustrated in previous studies. Demands imposed on tongue retraction, however, are different to some degree. Although in both groups there is a clear demand for …

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …

Identification And Characterization Of A New Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator (Rta)- Responsive Element Involved In Rta-Mediated Transactivation, Hui-Ju Wen, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is well established as a key transcriptional activator that regulates the KSHV life cycle from latency to lytic replication. It is expressed immediately after infection and activates a number of viral genes leading to virus replication. The RTA-responsive element (RRE) in the RTA target gene promoters is critical for RTA to mediate this transactivation. A number of non-conserved RREs have been identified in various RTA-responsive promoters, and AT-rich sequences have been proposed to serve as RTA targets, but no consensus RRE sequence has been identified so far. Two nonconserved RREs (RRE1 …

Use Of Average Mutual Information For Studying Changes In Hiv Populations, Khalid Sayood, Federico Hoffman, Charles Wood

Nebraska Center for Virology: Faculty Publications

Average mutual information (AMI) has been used in a number of applications in bioinformatics. In this paper we present its use to study genetic changes in populations; in particular populations of HIV viruses. Disease progression of HIV-1 infection in infants can be rapid resulting in death within the the first year, or slow, allowing the infant to survive beyond the first year. We study the development of rapid and slow progressing HIV population using AMI charts based on average mutual information among amino acids in the env gene from a population of 1142 clones derived from seven infants with slow …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Expression Of Semaphorin 3f And Its Receptors In Epithelial Ovarian Cancer, Fallopian Tubes, And Secondary Müllerian Tissues, Christina D. Drenberg, Sandra Livingston, Ren Chen, Patricia A. Kruk, Santo V. Nicosia

Pathology and Cell Biology Faculty Publications

While semaphorins and their receptors appear to play a role in tumor carcinogenesis, little is known about the role of semaphorin 3F (S3F) in epithelial ovarian cancer (EOC) development. Therefore, we sought to determine the clinical relationship between S3F and its receptors, neuropilin-2 (NP-2) and neuropilin-1 (NP-1) with EOC progression. We analyzed the immunohistological expression of S3F, NP-2, and NP-1 in clinical specimens of normal ovaries (N), benign cystadenomas (Cy), well-differentiated adenocarcinomas (WD), poorly-differentiated adenocarcinomas (PD), inclusion cysts (IC), paraovarian cysts (PC), and fallopian tubes (FT). Tissue sections were evaluated for staining intensity and percentage of immunoreactive epithelia. We found …

Pattern Recognition Of Longitudinal Trial Data With Nonignorable Missingness: An Empirical Case Study, Julia Hua Fang, Kimberly A. Espy, Maria L. Rizzo, Christian Stopp, Sandra A. Wiebe, Walter W. Stroup

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Methods for identifying meaningful growth patterns of longitudinal trial data with both nonignorable intermittent and drop-out missingness are rare. In this study, a combined approach with statistical and data mining techniques is utilized to address the nonignorable missing data issue in growth pattern recognition. First, a parallel mixture model is proposed to model the nonignorable missing information from a real-world patient-oriented study and concurrently to estimate the growth trajectories of participants. Then, based on individual growth parameter estimates and their auxiliary feature attributes, a fuzzy clustering method is incorporated to identify the growth patterns. This case study demonstrates that the …

Impact Of The Short-Term Consumption Of A Moderately High Fat Diet On Nitric Oxide Production And Bioavailibility, Kan Huang

Theses, Dissertations and Capstones

Nitric oxide (NO) plays an essential role in the regulation of numerous biological processes. Its bioavailability is assured by a well regulated balance between NO generation and NO removal. Disruptions in this balance contribute to the pathogenesis of various diseases, including hypertension, Alzheimer’s disease, diabetes mellitus and arthritis. Many factors contribute to the maintenance of NO bioavailability by controlling nitric oxide synthase (NOS) expression, NOS activity, the availability of substrates and cofactors involved in the generation of NO by NOS, levels of reactive oxygen species (ROS), and the formation and mobilization of NO reservoirs. Dietary factors have a significant impact …

Habitat Variation Among Aquatic Gastropod Assemblages Of Indiana, U.S.A., Mark Pyron, Jayson Beugly, Matthew Spielman, Jennifer Pritchett, Stephen J. Jacquemin

Biological Sciences Faculty Publications

We collected aquatic gastropods at 137 sites in lakes and streams of Indiana and tested for patterns of assemblages with environmental variables. The survey resulted in 32 species with a mean of 2.8 species at each site, and a mean abundance at each site of 144 individuals. Nonmetric multidimensional scaling (NMS) multivariate analyses resulted in watershed drainage area, water conductivity, substrate category frequency, and dissolved oxygen as significant correlates of gastropod assemblage structure. Gastropod assemblages of lakes were not significantly different than assemblages of streams in the ordination. Prosobranch taxa occurred in higher abundances than pulmonate taxa at sites with …

Persistencia De Anticuerpos Maternales Contra El Virus De La Peste Porcina Clásica En Lechones Nacidos De Marranas En Granjas Con Diferentes Estrategias De Vacunación, Katherine J. Portilla, Albert Manchego S., Hermelinda G. Rivera, Mariluz Araínga, Marcy Ramierz V.

Journal Articles: Pharmacology & Experimental Neuroscience

In the study evaluated was the persistence of maternal antibodies levels Classical Swine Fever Against the virus (CSFV) in Vaccinated piglets born from sows from two farms (A and B) With different strategies against CSFV vaccination. In farm A sows were vaccinated at 90 days of gestation and in farm B at 18 - 21 days postpartum. Serum samples were collected from piglets of both farms, at first (n=15), third (n=15), fifth (n=15) and seventh (n=15) weeks of age, and from 15 sows from each farm A for detection of antibodies against CSFV by the indirect ELISA test. All piglets …

Differential Effects Of Th1, Monocyte/Macrophage And Th2 Cytokine Mixtures On Early Gene Expression For Molecules Associated With Metabolism, Signaling And Regulation In Central Nervous System Mixed Glial Cell Cultures, Robert P. Lisak, Joyce A. Benjamins, Beverly Bealmear, Liljana Nedelkoska, Diane Studzinski, Ernest Retland, Bin Yao, Susan Land

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS) in multiple sclerosis (MS).

Methods

We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M).

Results

In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, …

Regulation Of Alpha- And Beta-Actin Isoforms In The Contracting A7r5 Smooth Muscle Cell, Dawn Leah Brown-Turner

Theses, Dissertations and Capstones

Two isoforms of actin have been found to be present in A7r5 smooth muscle cells, α- and β-actin. This body of work sets out to examine the different regulatory factors of the two actin isoforms during smooth muscle contraction. The response of the actin isoforms to phorbol 12, 13-dibutyrate (PDBu) is markedly different. α-Actin remodels to podosomes around the periphery of the cell, while β-actin merely shortens. One protein involved in smooth muscle contraction induced by PDBu is protein kinase C (PKC). Two inhibitors of PKC, staurosporine and bisindolymaleimide, were used prior to PDBu stimulation and after PDBu stimulation to …

Comparison Of Trauma Scores For Adults Who Fell From Height As Survival Predictivity, Mehmet Eryilmaz, Murat Durusu, Öner Menteş, Tahi̇r Özer, Seli̇m Kiliç, Gürkan Ersoy, Özcan Altinel, Murat Kalemoğlu, Nurkan Törer

Turkish Journal of Medical Sciences

Aim: Falls from a height and their subsequent injuries and traumas can cause morbidity and death. In the present study, ISS, NISS, RTS, and TRISS values were analyzed to assess mortality probabilities of patients who fell from a height. Materials and Methods: Patients' age, gender, height of falls (0-2 m, 3-5 m, and 6 m and above), organ pathologies, and ISS, NISS, RTS, and TRISS scores were evaluated in terms of mortality. Results: Regarding the survival rate, no statistically significant difference was found between age and gender (P > 0.05). We determined that all trauma scores were correlated with mortality, and …

Overactive Bladder Syndrome And Detrusor Overactivity: Is There A Strong Relation Between The Symptoms And Urodynamic Findings?, Orhan Ünal Zorba, Taner Koçak, Kadi̇r Önem

Turkish Journal of Medical Sciences

Aim: Overactive bladder (OAB) and detrusor overactivity (DO) may interfere because one may cause the other. Not all patients with OAB have DO, neither do all patients with DO have OAB. In our study the correlation between OAB symptoms and DO was investigated. Materials and Methods: In the present study, 190 patients with OAB and/or DO were investigated. Patients were divided into 3 groups: OAB with DO group (group 1, n = 63), DO without OAB group (group 2, n = 34), and OAB without DO group (group 3, n = 93). The symptoms and urodynamic findings of the patients …

Association Between Mean Platelet Volume And Autonomic Nervous System Functions: Increased Mean Platelet Volume Reflects Sympathetic Overactivity, Tahi̇r Durmaz, Özcan Özdemi̇r, Telat Keleş, Ni̇hal Akar Bayram, Murat Akçay, Ekrem Yeter, Hüseyi̇n Ayhan, Engi̇n Bozkurt

Turkish Journal of Medical Sciences

Aim: Increased mean platelet volume (MPV) may reflect increased platelet activation and accepted as an independent coronary risk factor. Adrenergic system has effects on platelet activation and thrombocytopoiesis. In this study, we assessed the effects of autonomic nervous system activity on MPV in patients with acute myocardial infarction (MI). Materials and Methods: Forty-seven patients with acute anterior MI were compared with 32 patients having normal coronary arteries. All patients underwent heart rate variability analysis by 24-h holter monitoring and blood samples were taken for MPV measurements during day and night times during holter monitoring. Results: Mean heart rate (HR), Low …

Mutational Analysis Of The Mefv Gene In Egyptian Patients With Familial Mediterranean Fever, Ayşenur Öztürk, Ezzat Elsobky, Solaf M. Elsayed, Mostafa Alhodhod, Nejat Akar

Turkish Journal of Medical Sciences

Aim: Familial Mediterranean fever is an autosomal recessive disease affecting primarily populations surrounding the Mediterranean basin. The aim of this study was to find the distribution of MEFV gene mutations in a group of Egyptian patients with FMF and to evaluate any predictive genotype-phenotype correlation in this group of patients. Materials and Methods: The study included 112 patients (59 males and 53 females). Sequencing of the exon 10, exon 3, and exon 5 and PCR/RFLP analysis of E148Q and R202Q mutations of exon 2 of the MEFV gene were performed for all the patients according to a previously described technique. …

A Simple Surgical Technique For Repair Of Iridodialysis, Şengül Özdek, Mehmet Cüneyt Özmen

Turkish Journal of Medical Sciences

A simple surgical technique is described for repair of iridodialysis and a traumatic iridodialysis case is presented. In this technique, a 10-0 polypropylene suture is used for repair. The knot is left in the anterior chamber to avoid suture related complications such as erosion, patient discomfort, and infection. This technique can be a safe and easy way to repair large iridodialysis.

Linear And Whorled Nevoid Hypermelanosis In Trisomy 13, Şengül Yüksel, Serap Savaci, Uğur Biçak, Cengi̇z Yakinci, Bülent Mizrak

Turkish Journal of Medical Sciences

Linear and whorled nevoid hypermelanosis (LWNH) is a reticulate pigmentary disorder with a sporadic occurrence, generally representing a genetic mosaicism. In this case, we describe a two-month-old girl with trisomy 13, who presented with various systemic anomalies such as congenital ventricular septal defect, microcephaly, auricular deformities, flatness of nasal root, overlapping fingers, umbilical hernia, and LWNH. G-banding chromosomal analyses were performed on cultured peripheral blood lymphocytes of the patient and the parents. The karyotype of the patient was 47, XX,+13[100], with no mosaicism. The karyotypes of the parents were normal. To our knowledge, we present the first patient with LWNH …

A Rare Case Of Pilomatricoma With Bullous Appearance, Ayşe Serap Karadağ, Meral Ekşi̇oğlu, Eki̇n Özlük, Gülfer Akbay, Alev Eken, Savaş Serel, Hesna Müzeyyen Astarci

Turkish Journal of Medical Sciences

Background: Pilomatricoma is a rare, benign adnexal tumor differentiating toward elements of the hair matrix and shaft. It typically presents as a solitary, deep, dermal nodule. In addition, bullous changes can be rarely seen. Methods: A 16-year-old girl with firm, mobile, multilobule and non-tender mass that has a soft, hemorrhagic blister-like formation on the left infraclavicular region is described. Results: The histopathologic findings were consistent with pilomatricoma. In the dermis above the tumor, there were numerous dilated lymphatic and blood vessels. No pathologic elastic fibrils were identified with elastin stains. Collagen fibrils were normal with Mason trichrome stain. Conclusions: The …

Local Reccurence Of Giant Renal Cell Carcinoma Without Distant Metastases 25 Years After Radical Nephrectomy, Turgut Yapanoğlu, Yilmaz Aksoy, İsa Özbey, Cemal Gündoğdu, Özkan Polat

Turkish Journal of Medical Sciences

A 64-year-old man underwent a left radical nephrectomy 25 years ago. The pathological examination revealed renal cell carcinoma (RCC) and no lymph node metastasis. He suffered a recurrence in the renal fossa 25 years after the operation. To our knowledge, this is the first report of late (about 25 years) recurrence of RCC without distant metastases after radical nephrectomy. The isolated fossa recurrence of RCC without any distant metastasis is very uncommon. We suggest that the patients with RCC who underwent radical nephrectomy should undergo lifelong follow up.