Digital Commons Network^™

Chronic Acetaminophen Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fisher 344 X Brown Norway Rat Aorta, Sarath Meduru

Theses, Dissertations and Capstones

We have previously reported that aging in the Fisher 344 X Brown Norway (FBN) rat aorta is characterized by increased levels of ROS and alterations in cell signaling. Acetaminophen was found to scavenge free radicals in recent ischemia-reperfusion studies. Here we examined if chronic treatment with a therapeutic dose of acetaminophen attenuates age-associated increase in aortic ROS accumulation and signaling. FBN rats (27 month old; n=8) were subjected to 6 months of treatment with a therapeutic dose of acetaminophen (30mg/kg/day), with age-matched untreated FBN rats as controls. Protein oxidation levels were altered in control and treated aortae compared to aortae …

The Expression And Function Of Ppar And Hif-1 In Human Melanoma, Caroline Mills

Theses, Dissertations and Capstones

The first part of my dissertation focuses on the expression and function of PPARs in human melanoma. I found that the A375 cells were significantly growth inhibited in response to _PGJ2 and troglitazone treatment. HEMn-LP showed significant growth inhibition in response to troglitazone. I found that PPARγ and PPARδ mRNA is present in both the SK-Mel 28 and A375 cells. The relative level of PPARα mRNA expression is highest in SK-Mel 28 cells, ~3 fold higher relative to both the normal human melanocytes and A375 cells. PPARγ protein was ~50% higher in both SK-Mel 28 and A375 cells relative to …

Aging Influences Multiple Indices Of Oxidative Stress In The Heart Of The Fischer 344/Nnia X Brown Norway/Binia Rat, Shinichi Asano

Theses, Dissertations and Capstones

Here we report the influence of aging on multiple markers of oxidativenitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36- month) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Compared to 6 month old rat hearts, indices of oxidative (superoxide anion (–O2 ·), 4-hyrdoxy-2- nonenal (4-HNE)) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r>0.669; r>0.710 and p<0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.

Lean And Obese Zucker Rats Exhibit Different Patterns Of P70s6kinase Regulation In The Tibialis Anterior Muscle In Response To High Force Muscle Contraction, Anjaiah Katta

Theses, Dissertations and Capstones

Increased muscle loading results in phosphorylation of the 70 kDa ribosomal S6 kinase (p70s6k) signaling pathway and this event strongly correlates with degree of muscle adaptation following resistance exercise. Here, we compared the basal and contraction- induced phosphorylation of p70s6k, Akt and mTOR in tibialis anterior muscles of lean and obese Zucker rats. Immunoblotting demonstrated differences in level of basal p70S6k phosphorylation (Thr 389) in the normal and diabetic TA. HFES had an increase in p70S6k (Thr389) phosphorylation at 0-, 1- and 3-hr in lean TA and only at 3-hr in obese TA. mTOR (Ser 2448) Phosphorylation was elevated in …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

MIIR Faculty Research

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …

Fusion, 2007, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

The Glutamate And Chloride Permeation Pathways Are Colocalized In Individual Neuronal Glutamate Transporter Subunits, Gregory Patrick Leary, Emily F. Stone, David Charles Holley, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Glutamate transporters have a homotrimeric subunit structure with a large central water-filled cavity that extends partially into the plane of the lipid bilayer (Yernool et al., 2004). In addition to uptake of glutamate, the transporters also mediate a chloride conductance that is increased in the presence of substrate. Whether the chloride channel is located in the central pore of the trimer or within the individual subunits has been controversial. We find that coexpression of wild-type neuronal glutamate transporter EAAT3 subunits with subunits mutated at R447, a residue governing substrate selectivity (Bendahan et al., 2000), results in …

Health Professions Division Catalog 2007-2008, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Physical Characteristics Of An Individual: The Identification Of Biomarkers For Biological Age Determination, Michelle Alvarez

Electronic Theses and Dissertations

It is now a matter of routine for the forensic scientist to obtain the genetic profile of an individual from DNA recovered from a biological stain deposited at a crime scene. Potential contributors of the stain must either be known to investigators (i.e. a developed suspect) or the questioned profile must be searched against a database of DNA profiles such as those maintained in the CODIS National DNA database. However, in those instances where there is no developed suspect and no match is obtained after interrogation of appropriate DNA databases, the DNA profile per se presently provides no meaningful information …

Humor And Laughter May Influence Health [Part] Iv. Humor And Immune Function, Mary Payne Bennett, Cecile Lengacher

Nursing Faculty Publications

This is the final article in a four part series reviewing the influence of humor and laughter on physiological and psychological well-being. This final article reviews the evidence for the effect of sense of humor, exposure to a humor stimulus and laughter on various immune system components, with a focus on the effects of laughter on natural killer cell cytotoxicity.

Depression: Relationships To Sleep Paralysis And Other Sleep Disturbances In A Community Sample, Mariana Szklo-Coxe, Terry Young, Laurel Finn, Emmanuel Mignot

Community & Environmental Health Faculty Publications

Sleep disturbances are important correlates of depression, with epidemiologic research heretofore focused on insomnia and sleepiness. This epidemiologic study’s aim was to investigate, in a community sample, depression’s relationships to other sleep disturbances: sleep paralysis (SP), hypnagogic/hypnopompic hallucinations (HH), cataplexy – considered rapid eye movement-related disturbances – and automatic behavior (AB). Although typical of narcolepsy, these disturbances are prevalent, albeit under-studied, in the population. Cross-sectional analyses (1998–2002), based on Wisconsin Sleep Cohort Study population-based data from 866 participants (mean age 54, 53% male), examined: depression (Zung Self-Rating Depression Scale), trait anxiety (Spielberger State-Trait Anxiety Inventory, STAI-T ≥ 75th percentile), and …

Chimpanzee Research: An Examination Of Its Contribution To Biomedical Knowledge And Efficacy In Combating Human Diseases, Jarrod Bailey, Jonathan Balcombe, Theodora Capaldo

Experimentation Collection

Research on captive chimpanzees incurs considerable animal welfare, ethical and financial costs. Advocates of such research claim these costs are outweighed by substantial advancements in biomedical knowledge, and that the genetic similarity of chimpanzees to humans enables the former to make critical contributions to preventing, diagnosing and combating human diseases. To assess these claims, we examined the disciplines investigated in 749 studies of captive chimpanzees published from 1995-2004 inclusive, and subjected 95 randomly selected papers to a detailed citation analysis:

49.5% (47/95) of papers had not been cited at the time of this study; 38.5% (34/95) were cited by 116 …

Association Of Smooth Muscle Myosin And Its Carboxyl Isoforms With Actin Isoforms In Aorta Smooth Muscle, Jason Edward Black

Theses, Dissertations and Capstones

The contraction mechanism of smooth muscle is not fully understood. The primary interaction that leads to the formation of tension, the myosin-actin crossbridge, has been studied extensively. However, even this aspect of the contraction has proven not to be as simple as it might seem. There are several isoforms of smooth muscle myosin and actin, and the differences in the activities of these isoforms and their interactions during the contractile process are largely unknown. The studies to be discussed are directed at the determination of the interaction of these isoforms during the contraction of rat aortic smooth muscle. Chapter II …

Anosognosia In Mild Cognitive Impairment: Relationship To Activation Of Cortical Midline Structures Involved In Self-Appraisal, Michele L. Ries, Britta M. Jabbar, Taylor W. Schmitz, Mehul A. Trivedi, Carey E. Gleason, Cynthia M. Carlsson, Howard A. Rowley, Sanjay Asthana, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI …

Atypical Antipsychotics And Cognitive Enhancement In Schizophrenia: The Current Status, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Cognition As An Outcome Measure In Schizophrenia, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Differential Effects Of Th1, Monocyte/Macrophage And Th2 Cytokine Mixtures On Early Gene Expression For Glial And Neural-Related Molecules In Central Nervous System Mixed Glial Cell Cultures: Neurotrophins, Growth Factors And Structural Proteins, Robert P. Lisak, Joyce A. Benjamins, Beverly Bealmear, Liljana Nedelkoska, Bin Yao, Susan Land, Diane Studzinski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells.

Methods

To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the …

Age-Related Dgc Structure And Function In The F344/N X Bn Rat Heart, Sunil K. Kakarla

Theses, Dissertations and Capstones

Recent data has suggested that disruption of the dystrophin-glycoprotein complex (DGC) may be involved in mediating the progression of cardiac hypertrophy and failure. Here we examined the regulation of DGC proteins in the hearts of adult (6 months), aged (30 months), and very aged (36 months) F344/N X BN rats . Compared to adult animals, the content of α- and β-dystroglycan were 6.93 ± 5.16% and 58.36 ± 3.64% higher, respectively (P < 0.05) in very aged animals. Immunoblotting and immunhistochemical analysis suggested that aging appeared to diminish alpha-sarcoglycan, beta-sarcoglycan and delta-sarcoglycan content by 13.89 ± 3.1%,15.8 ± 2.8% and 18.63 ± 3.04%, respectively (P < 0.05). These alterations in the DGC occurred coincident with age- associated alterations in cytoplasmic anti-rat IgG immunoreactivity, TUNEL positive nuclei, alpha-fodrin cleavage, indices of caspase-3 activation and diminished AKT phosphoryation (Ser 308). Taken together, these data suggest that aging alters cardiac DGC structure and function.

Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Barrier to autointegration factor (BAF) is a DNA-binding protein found in the nucleus and cytoplasm of eukaryotic cells that functions to establish nuclear architecture during mito-sis. Herein, we demonstrate a cytoplasmic role for BAF in host defense during poxviral infections. Vaccinia is the prototypic poxvirus, a family of DNA viruses that replicate ex-clusively in the cytoplasm of infected cells. Mutations in the vaccinia B1 kinase (B1) com-promise viral DNA replication, but the mechanism by which B1 achieves this has remained elusive. We now show that BAF acts as a potent inhibitor of poxvirus replication unless its DNA-binding activity is blocked …

Dietary Behaviors And Anthropometric Measurements Of Mexican Women And Second Generation Mexican American Women, Liane Fernyhough

Undergraduate Honors Theses

Risk for chronic diseases is higher among Mexican Americans than in the general American population. A high percentage of central Washington Mexican Americans (CWMAs) immigrated from Michoacan, Mexico. The purpose of this study was to determine if dietary behaviors differ between women living in these areas and if these differences were associated with physiological differences. Sixty-one women (ages 18-50) in Morelia Michoacan and 26 second-generation CWMA women (ages 18-50) participated. Body mass index tended to be higher in the CWMA women (32±7 vs. 29±6, p≤0.06) as was waist circumference (39±7 vs 36±5 inches, p≤0.06). those surveyed in both Michoacan and …

Role Of Protein Kinase Phosphorylation On Sert Oligomerization: A Novel Mechanistic View, Eric Richard Buck

MUSC Theses and Dissertations

The serotonin transporter (SERT) is the primary mechanism for the termination of synaptic signaling. It is of clinical relevance because it is a high-affinity target for therapeutics such as anti-depressants (SSRIs) and drugs of abuse such as cocaine, amphetamine, and 3,4 methylenedioxymethamphetamine (ecstasy). It is also seen as a protein potentially involved in the etiology underlying disorders such as clinical depression, autism, anxiety-related disorders, obsessive compulsive disorder, and anorexia nervosa among others. SERT has also been found to be a target of protein kinases that exert their effects through phosphorylation. For example, activation of protein kinase C (PKC) decreases SERT …

Letter To The Editor: Further Efforts To Redce The Incidence Of Neural Tube Defects, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Triumph And/Or Tragedy: The Present Food And Drug Administration Program Of Enriching Grains With Folic Acid., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Developmental Toxicology Drugs, And Fetal Teratogenesis, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Robert Warwick Miller: In Memoriam., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

How Does The Physician Avoid Prescribong Drugs And Medical Procedures That Have Reproductive And Developmental Risks?, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Replication Fork Regression In Vitro By The Werner Syndrome Protein (Wrn): Holliday Junction Formation, The Effect Of Leading Arm Structure And A Potential Role For Wrn Exonuclease Activity, Amrita Machwe, Liren Xiao, Robert G Lloyd, Edward Bolt, David K. Orren

Toxicology and Cancer Biology Faculty Publications

The premature aging and cancer-prone disease Werner syndrome stems from loss of WRN protein function. WRN deficiency causes replication abnormalities, sensitivity to certain genotoxic agents, genomic instability and early replicative senescence in primary fibroblasts. As a RecQ helicase family member, WRN is a DNA-dependent ATPase and unwinding enzyme, but also possesses strand annealing and exonuclease activities. RecQ helicases are postulated to participate in pathways responding to replication blockage, pathways possibly initiated by fork regression. In this study, a series of model replication fork substrates were used to examine the fork regression capability of WRN. Our results demonstrate that WRN catalyzes …

Fa2h Dependent Fatty Acid 2-Hydroxylation In The Mammalian Nervous System, Nathan Lance Alderson

MUSC Theses and Dissertations

Myelin is formed by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. This unique membrane is comprised of approximately 70% lipid and 30% protein. The high lipid content is thought to be vital for its insulatory function. Galactosylceramide (GaICer) and sulfatide make up approximately 30% of total myelin lipids, with more than half of these galactolipids containing fatty acids hydroxylated at the C[subscript 2] position (2-hydroxy fatty acids). Despite their high abundance, very little is know about the biosynthesis of these 2-hydroxy galactolipids, and specific functions of the 2-hydroxyl group in myelin galactolipids remain …

Telomerase Inhibition And Sensitization Of Breast Tumor Cells, Kennon R. Poynter

Theses and Dissertations

Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anticancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditions chemo- and radio-therapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities.While various …

Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5α. We modeled the structure of the B-box 2 domain of TRIM5α based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5αhu or rhesus monkey TRIM5α_rh. However, alteration of arginine 119 of TRIM5α_hu or the corresponding arginine 121 of TRIM5α_rh diminished the abilities of …