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Inflammation: The Key To Health And Disease, Prakash Nagarkatti Ph. D, Donald J. Dipette M. D.

Journal of the South Carolina Academy of Science

No abstract provided.

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for conjugation. We further …

The Relationship Between Carnitine Levels And Lipid Peroxidation In Glial Brain Tumors, Ni̇lüfer Bayraktar, Hati̇ce Paşaoğlu, Aydin Paşaoğlu, Memduh Kaymaz, Gürsel Bi̇beroğlu, Sevsen Kulaksizoğlu

Turkish Journal of Medical Sciences

Aim: It is assumed that reactive oxygen species and lipid peroxidation cause cell membrane damage and play a role in oncogenesis. Carnitine and acyl esters, which play a role in intracellular short-, medium-, and long-chain fatty acid metabolism, are one of the defense mechanisms against free radical toxicity. It is thought that the protective effects of carnitine are related with its role in lipid metabolism. In our study, we analyzed the relation between malondialdehyde (MDA) and free carnitine, and C2, C3, C4, C5, C6, C8, C10, C12, C14:1, C14, C16:1, C16, C18:1, C18, C20:4 carnitine levels in glial tumors [glioblastoma …

Is The Gök Atlas Sufficiently Reliable For Forensic Age Determination Of Turkish Children?, Bora Büken, Erhan Büken, Alp Alper Şafak, Burhan Yazici, Zerri̇n Erkol, Ati̇lla Mayda

Turkish Journal of Medical Sciences

Aim: We investigated whether the contemporary use of the Gök Atlas method is sufficiently reliable for forensic age estimations of Turkish children. Materials and Methods: Plain radiographs of 248 females and 298 males between 11 and 22 years of age were taken. Paired sample t-tests, Pearson correlation coefficients, and linear regression were used to determine the differences and model the relationships between mean skeletal (bone) age (BA) and mean chronological age (CA), using SPSS 11.5 statistical software. Results: In all cases, the CA and BA scores were significantly different and showed high correlation (P < 0.05). The regression model was significant (P < 0.01). According to age groups, the BA was greater than the CA for all age groups by 0.09-3.10 years for boys and 0.44-3.05 years for girls, and this difference was significant for all age groups >14 years for boys and for …

A Novel Method For The Production Of Potentially Therapeutic Human Monoclonal Antibodies In Vitro, Adria L. Bykowski

MUSC Theses and Dissertations

We have developed a novel approach for the production of potentially therapeutic human monoclonal antibodies in vitro. This method holds great promise for generating therapeutic antibodies against infectious disease, cancer, and inflammation. The complex nature of current methods for producing human monoclonal antibodies is a major impediment to large scale passive transfer immunotherapy. Our novel technique utilizes Epstein-Barr virus immortalized tonsil or peripheral blood B cells from healthy human volunteers. These B cells are forced to undergo non-specific differentiation to become mature IgG antibody producing plasma "like" cells that continuously proliferate in vitro. Using this method, millions of transformed B …

Gender Bias Of Cardiovascular Risk In Caucasian Type Ii Diabetics: A Haemostatic Explanation?, William Quirke

Theses

People with type II diabetes are disproportionately affected by cardiovascular disease compared to those without diabetes. The relative risk of cardiovascular disease caused by type II diabetes is higher in females than in males. This risk has not been fully explained by traditional risk factors and attention has turned to the possible role of haemostatic abnormalities in explaining the excess cardiovascular morbidity and mortality among diabetic females. We examined specific parameters of the coagulation (factor VII, factor VIII, von Willebrand factor, fibrinogen) and fibrinolytic (plasminogen activator inhibitor- 1, thrombin-activatable fibrinolysis inhibitor) system in 113 Irish Caucasian type II diabetics to …

Role Of Reactive Oxygen Species Peroxynitrite In Traumatic Spinal Cord Injury, Yiqin Xiong

University of Kentucky Doctoral Dissertations

Peroxynitrite (PN, ONOO-), formed by nitric oxide radical (^•NO) and superoxide radical (O2^•-), plays an important role in post-traumatic oxidative damage. In the early work, we determined the temporal characteristics of PN-derived oxidative damage in a rat spinal cord injury (SCI) model. Our results showed 3-nitrotyrosine (3-NT), a specific marker for PN, rapidly accumulated at early time points (1 hr, 3 hrs), after when it plateaued and the high level was sustained to 1 week post injury. The co-localization of 3-NT and lipid peroxidation derived-4-HNE observed in immunohistochemistry indicates PN is involved in lipid peroxidative as …

The Underlying Mechanism(S) Of Fasting Induced Neuroprotection After Moderate Traumatic Brain Injury, Laurie Michelle Helene Davis

University of Kentucky Doctoral Dissertations

Traumatic brain injury (TBI) is becoming a national epidemic, as it accounts for 1.5 million cases each year. This disorder affects primarily the young population and elderly. Currently, there is no treatment for TBI, which means that ~2% of the U.S. population is currently living with prolonged neurological damage and dysfunction. Recently, there have been many studies showing that TBI negatively impacts mitochondrial function. It has been proposed that in order to save the cell from destruction mitochondrial function must be preserved. The ketogenic diet, originally designed to mimic fasting physiology, is effective in treating epilepsy. Therefore, we have used …

Analysis Of Hiv-1 Variable Loop 3-Specific Neutralizing Antibody Responses By Hiv-2/Hiv-1 Envelope Chimeras, Katie L. Davis

All ETDs from UAB

Defining the epitope specificities of the neutralizing antibody response to the HIV-1 envelope protein (Env) during natural human infection and in response to vaccination by HIV-1 immunogens could provide insight into the mechanisms of virus immune containment and facilitate vaccine design. Transplantation of discrete HIV-1 neutralizing epitopes into HIV-2 Env scaffolds may provide a sensitive, biologically functional context in which to quantify specific antibody reactivities in complex sera. Here we describe the development of a novel HIV-2 proviral scaffold (pHIV-2KR.X7) into which we have substituted the env V3 region of several laboratory and primary HIV-1 strains to yield a panel …

The Role Of Tgfß Signaling In Skeletal Development, Hwa-Seon Seo

All ETDs from UAB

skeletal element is essential for body movement along with the joints, muscles, tendons and ligaments. They also protect internal organs and serve as a reservoir for hematopoietic stem cells and minerals. To accomplish these multiple tasks, the size and shape of the skeletal elements need to be carefully designed during development of the embryo. Skeletal formation in vertebrae is a complex developmental processes controlled by dynamic and well-balanced interactions between a number of molecular signals. Intensive efforts in the past several decades have made substantial progress in understanding molecular and cellular mechanisms of skeletal development. Despite the fact that TGFß …

Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar

All ETDs from UAB

Cholangiocarcinoma, a fatal tumor arising from biliary epithelium, has very poor 5-year survival rate due to lack of early diagnosis and effective therapies. Induction of the Fas-mediated apoptosis is a promising therapeutic target in this tumor. Studies from our group and others have indicated that Fas-expression correlates inversely with disease progression and that CaM-antagonists induce apoptosis in cholangiocarcinoma cells in a Fas related manner. Further, we reported a direct and dynamic interaction of CaM and Fas and that CaM is recruited into the Fas-stimulated death inducing signaling complex (DISC), suggesting a cross talk between Fas and CaM pathways. The studies …

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 …

Solution Chemical Synthesis Of Nanostructured Thermoelectric Materials, Xiaohua Ji, Terry M. Tritt, Xinbing Zhao, Joe W. Kolis

Journal of the South Carolina Academy of Science

No abstract provided.

Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh

All ETDs from UAB

Many different tumors have been documented to have elevated levels of the enzyme ST6Gal I, a Golgi glycosyltransferase that adds α2-6 sialic acids to glycoproteins. Concurrently, upregulated ST6Gal I is associated with metastasis and poor patient prognosis. We initially showed that HD3 colonocytes made to express oncogenic-ras, a common mutation in colon carcinoma, have increased expression of ST6Gal I and elevated α2-6 sialylated integrins. Having established that ras regulates ST6Gal I expression in colon epithelial cells, we found that colonocytes carrying hyper α2-6 sialylated β1 integrins exhibit increased adhesion to and migration toward collagen I. Further, we found that β1 …

Biological Variation And Reference Change Values Of Tsh, Free T3, And Free T4 Levels In Serum Of Healthy Turkish Individuals, Gönül Erden, Ayşe Özden Barazi̇, Günay Tezcan, Meti̇n Yildirimkaya

Turkish Journal of Medical Sciences

Aim: Thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) levels in serum are important for diagnosis of thyroid dysfunction. Thyroid function tests have considerable biological variations. Evaluation of the components of biological variation is essential to assess the usefulness of reference values and to evaluate significance of changes in serial results from an individual. Published estimates may show disagreement about the values of biological variations. Not many studies exist at present that evaluate the reference change values (RCV) of these parameters. The aim of this study was to determine the biological variations of TSH, free T3, and free T4 and to …

Pten Expression In Primary Prostate Carcinoma In Turkish Patients, Di̇lek Ertoy Baydar, Haluk Özen, Osman Saraçbaşi, Erdem Karabulut

Turkish Journal of Medical Sciences

Aim: Prostatic adenocarcinoma shows remarkable variability in the incidence and biological behavior between populations from different races and geographical regions of the world. PTEN has been reported as the most commonly mutated tumor suppressor gene in prostate cancer. Incidence of PTEN alterations occurring in prostatic carcinoma has not been studied previously in the Turkish population. Materials and Methods: We examined PTEN protein expression immunohistochemically and its significance in 69 primary prostate cancer patients from Turkey. Two tissue microarrays constructed by 0.6 mm cores from radical prostatectomy specimens were used. Clinical information for all patients was obtained from hospital records. Results: …

Oxidative Stress Of Radioiodine Treatment In Patients With Hyperthyroidism, Mustafa Yildiz, Ekrem Çi̇çek, Burçi̇n Aşkim Gümüş, Celal Çerçi̇, Süreyya Çerçi̇, Erol Eroğlu, Namik Deli̇baş

Turkish Journal of Medical Sciences

Aims: To investigate radiation-induced oxidative damage in erythrocytes after administration of radioiodine-131 (^{131}I) in patients with hyperthyroidism. Materials and Methods: Twenty patients with hyperthyroidism (11 F, 9 M) treated with ^{131}I were included into the study. Blood samples were taken from patients just before, 1 hour after and 3 hours after applying radioiodine. Malondialdehyde (MDA) and levels of antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) were measured to evaluate the radiation-induced oxidative damage. Results: We found that enzyme activities of SOD, GPX and CAT were decreased 1 hour and 3 hours after radioiodine treatment …

Clinical And Rhinoscintigraphic Evaluation Of Oral Macrolides In The Management Of Sinonasal Polyposis, Emi̇ne Aydin, Hülya Ortapamuk, Hakan Korkmaz, Engi̇n Dursun, Adi̇l Eryilmaz, Güleser Saylam, Muharrem Dağli

Turkish Journal of Medical Sciences

Aim: To document the efficacy of low-dose long-term oral macrolide treatment in the management of sinonasal polyposis. The study was designed prospectively in a group of patients with sinonasal polyposis and negative history of surgery. Materials and Methods: Ten patients were administered roxithromycin (RXM) 150 mg/day single oral dose for eight weeks. All patients underwent Tc-99m rhinoscintigraphic evaluation of mucociliary activity and endoscopic evaluation before and after the treatments. Response to treatment, in terms of rhinoscintigraphic and endoscopic improvement, was assessed. Results: Of the 10 patients, 7 were male and 3 female, with an average age of 46 years (27-74). …

Induction Of The Heat Shock Response To Protect Against Polyglutamine Diseases And The Role Of Protein Sumoylation In Laminopathies And Alzheimer's Disease, Yu-Qian Zhang

University of Kentucky Doctoral Dissertations

Heat shock proteins function as molecular chaperones which help protein folding and prevent protein aggregation. My study shows that celastrol, a pharmacological compound capable of up-regulating the levels of heat shock proteins, inhibits cell death and protein aggregation caused by expanded polyglutamine containing protein, and the protective effects of celastrol are dependent on heat shock factor 1. These results suggest the potential of celastrol as a therapeutic agent in the treatment of polyglutamine diseases.

Sumoylation is a protein modification which plays diverse roles in regulating the target proteins. My study shows that lamin A is a target of protein sumoylation, …

Nitration And Inactivation Of Manganese Superoxide Dismutase Plays A Critical Role In Metabolic Switch, Muthuswamy Anantharaman

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD) is a multifactorial, progressive, age-related neurodegenerative disease. Oxidative stress hypothesis is most prevalent and is gaining significant support. Inspite of the progress achieved on oxidative stress related damages in AD brain; the modification occurring on the various cellular antioxidant enzymes antioxidant has not been identified. Tyrosine nitration, a marker for peroxynitrite induced oxidative damage to protein is widespread in AD brain and Manganese superoxide dismutase (MnSOD), primary mitochondrial antioxidant enzyme is prone to peroxynitrite induced nitration and inactivation. Nitration of proteins involved in energy metabolism has been demonstrated in AD brain, which may explain the altered glucose …

Reciprocal Regulation Of Par-4 And Caspase-8 In The Trail Signaling Pathway, Padhma Ranganathan

University of Kentucky Doctoral Dissertations

Par‐4 is a pro‐apoptotic tumor suppressor that is mutated, suppressed or inactivated in cancer. Par‐4 exploits components of the extrinsic pathway to cause apoptosis selectively of cancer cells. This study identified Par‐4 as an essential component of the apoptotic pathway induced by TRAIL, which selectively targets cancer cells. RNA interference‐mediated knockdown of Par‐4 rendered cancer cells unresponsive to TRAIL‐induced apoptosis. Cells with knocked‐down levels of Par‐4 were deficient in the activation of the apoptosis‐initiator caspase‐8 and the apoptosis‐effector caspase‐3 in response to TRAIL. Par‐4 was identified as a critical mediator of membrane translocation of caspase‐8 and the adapter protein FADD. …

Stressor- And Corticotropin Releasing Factor-Induced Reinstatement And Active Stress-Related Behavioral Responses Are Augmented Following Long-Access Cocaine Self-Administration By Rats, John R. Mantsch, David A. Baker, David M. Francis, Eric S. Katz, Michael A. Hoks, Joseph P. Serge

Biomedical Sciences Faculty Research and Publications

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness.

Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA).

Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and …

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 …

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.

Cell Autonomous Expression Of Inflammatory Genes In Biologically Aged Fibroblasts Associated With Elevated Nf-Kappab Activity., Andres Kriete, Kelli L Mayo, Nirupama Yalamanchili, William Beggs, Patrick Bender, Csaba Kari, Ulrich Rodeck

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Chronic inflammation is a well-known corollary of the aging process and is believed to significantly contribute to morbidity and mortality of many age-associated chronic diseases. However, the mechanisms that cause age-associated inflammatory changes are not well understood. Particularly, the contribution of cell stress responses to age-associated inflammation in 'non-inflammatory' cells remains poorly defined. The present cross-sectional study focused on differences in molecular signatures indicative of inflammatory states associated with biological aging of human fibroblasts from donors aged 22 to 92 years. RESULTS: Gene expression profiling revealed elevated steady-state transcript levels consistent with a chronic inflammatory state in fibroblast cell-strains …

Development Of An Immunofluorescence Assay Using Recombinant Proteins Expressed In Insect Cells To Screen And Confirm Presence Of Human Herpesvirus 8-Specific Antibodies, Veenu Minhas, Lynsey N. Crosby, Kay L. Crabtree, Saul Phiri, Tendai J. M'Soka, Chipepo Kankasa, William J. Harrington, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

Human herpesvirus 8 (HHV-8), or Kaposi’s sarcoma (KS)-associated herpesvirus, has been linked to all forms of KS. The results of most current serological assays for the detection of HHV-8-specific antibodies have low levels of concordance among themselves. To establish a sensitive and specific testing strategy that can be used to screen for HHV-8-specific antibodies, three HHV-8 proteins, ORF65, ORF73, and K8.1A, were expressed by using baculoviral vectors in insect cells and incorporated into a monoclonal antibodyenhanced immunofluorescence assay (mIFA) termed the Sf9 three-antigen mIFA. The results obtained by this mIFA were compared to those obtained by a standard mIFA with …

Small-Molecule Cd4 Mimics Interact With A Highly Conserved Pocket On Hiv-1 Gp120, Navid Madani, Arne Schön, Amy M. Princiotto, Judith M. Lalonde, Joel R. Cpurter, Takahiro Soeta, Danny Ng, Liping Wang, Evan T. Brower, Shi-Hua Xiang, Young Do Kwon, Chih-Chin Huang, Richard Wyatt, Peter D. Kwong, Ernesto Freire, Amos B. Smith Iii, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV-1) interaction with the primary receptor, CD4, induces conformational changes in the viral envelope glycoproteins that allow binding to the CCR5 second receptor and virus entry into the host cell. The small molecule NBD-556 mimics CD4 by binding the gp120 exterior envelope glycoprotein, moderately inhibiting virus entry into CD4-expressing target cells, and enhancing CCR5 binding and virus entry into CCR5-expressing cells lacking CD4. Studies of NBD-556 analogues and gp120 mutants suggest that: 1) NBD-556 binds within the Phe 43 cavity, a highly conserved, functionally important pocket formed as gp120 assumes the CD4- bound conformation; 2) the NBD-556 …

The Human Immunodeficiency Virus Type 1 Envelope Confers Higher Rates Of Replicative Fitness To Perinatally Transmitted Viruses Than To Nontransmitted Viruses, Xiaohong Kong, John T. West, Hong Zhang, Danielle M. Shea, Tendai J. M’Soka, Charles Wood

Nebraska Center for Virology: Faculty Publications

Selection of a minor viral genotype during perinatal transmission of human Immunodeficiency virus type 1

(HIV-1) has been observed, but there is a lack of information on the correlation of the restrictive transmission

with biological properties of the virus, such as replicative fitness. Recombinant viruses expressing the enhanced

green fluorescent protein or the Discosoma sp. red fluorescent (DsRed2) protein carrying the V1 to V5

regions of env from seven mother-infant pairs (MIPs) infected by subtype C HIV-1 were constructed, and

competition assays were carried out to compare the fitness between the transmitted and nontransmitted

viruses. Flow cytometry was used to …