Digital Commons Network^™

Utilization Of Juvenile Animals Studies To Determine The Human Effects And Risks Of Environmental Toxicants During Postnatal Developmental Stages, Robert L. Brent

The Selected Works of Robert Brent

Toxicology studies utilizing animals and in-vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Testing in animals could be improved if animal dosing using the mg/kg basis was abandoned and drugs and chemicals were administered to compare the effects of pharmacokinetically and toxicokinetically equivalent serum levels in the animal model and human. Since alert physicians or epidemiology studies, not animal studies have discovered most human teratogens and toxicities …

Atypical Microtia Correction With Multiple Z-Plasties, Safvet Örs, Gali̇p K. Günay

Turkish Journal of Medical Sciences

RS^1, Galip K. GÜNAY^2 ^1Department of Plastic Surgery, Güneş Hospital, Kayseri - Turkey ^2Department of Plastic Surgery, Faculty of Medicine, Erciyes University, Kayseri - Turkey

Expression Analysis Of Dek, Af4 And Fli1 Genes In All-Trans-Retinoic Acid (Atra) Treated Acute Promyelocytic Leukaemia T(15;17) Patients By Quantitative Real-Time Pcr, Hakan Savli, Sema Sirma, Balint Nagy, Meli̇h Aktan, Günçağ Di̇nçol, Zafer Salcioğlu, Uğur Özbek

Turkish Journal of Medical Sciences

All-trans retinoic acid (ATRA) sensitivity of acute promyelocytic leukaemia (APL) cells is strictly dependent on the presence of t(15;17), but the molecular background of this sensitivity remains obscure. We showed the down- regulation of DEK, AF4 and FLI1 genes in the vitamin D treatment of APL cell line HL-60 , using cDNA array technology in our previous study. This finding prompted us to investigate the expression of these genes in APL patient samples. The effect of ATRA was studied in 6 APL patients carrying t(15;17). Two samples from each patient were compared with a primary diagnostic sample and a sample …

Incremental Genetic K-Means Algorithm And Its Application In Gene Expression Data Analysis, Yi Lu, Shiyong Lu, Farshad Fotouhi, Youping Deng, Susan J. Brown

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In recent years, clustering algorithms have been effectively applied in molecular biology for gene expression data analysis. With the help of clustering algorithms such as K-means, hierarchical clustering, SOM, etc, genes are partitioned into groups based on the similarity between their expression profiles. In this way, functionally related genes are identified. As the amount of laboratory data in molecular biology grows exponentially each year due to advanced technologies such as Microarray, new efficient and effective methods for clustering must be developed to process this growing amount of biological data.

Results

In this paper, we propose a new clustering …

Common Anorectal Conditions, Pravin J. Gupta

Turkish Journal of Medical Sciences

No abstract provided.

The Effects Of Asthma Education On Knowledge, Behavior And Morbidity In Asthmatic Patients, Rezan Demi̇ralay

Turkish Journal of Medical Sciences

This work was carried out to study the effect of asthma education on asthma knowledge, behavior and morbidity in asthmatic patients. A randomized double blind controlled study was conducted with 54 adults with asthma followed-up at the outpatient clinic of Chest Diseases and Tuberculosis at the Faculty of Medicine of Suleyman Demirel University. Patients were randomized to the verbal (n: 17), written (n: 19), and verbal-written (n: 18) education groups. Knowledge of asthma was measured at the baseline, and 2 months and 1 year after education. Compliance with treatment, correct inhaler skill and admisssons to hospital in the previous year …

Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green

Dartmouth Scholarship

LP-BM5 retrovirus-infected C57BL/6 mice develop splenomegaly, lymphadenopathy, hypergammaglobulinemia, and immunodeficiency; thus, this disease has been named mouse AIDS. In this syndrome, CD154/CD40 interactions are required for but do not mediate disease by upregulation of CD80 or CD86. We report here that there is nonetheless a necessity for CD40 signaling competence, specifically an intact tumor necrosis factor receptor-associated factor 6 (TRAF 6) binding site.

Thermodynamic Consequences Of Dna Base Modifications And Ligand-Dna Interactions., Rachel Hutchins Graves

All ETDs from UAB

The thermodynamic effects of alterations of the DNA duplex by DNA base modifications or ligand binding are investigated by a combination of spectrophotometric and calorimetric methods. Examination of the effects of substituent modification on the DNA binding energetics of the anticancer agent AAC (Y-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide) indicated that DNA binding affinities and energetics were enhanced upon substitution at the C5 position on the chromophore of the drug with a variety of chemical groups. A correlation between enthalpies of DNA binding and anticancer activity was evident.The impacts of DNA base modifications, including cytosine arabinoside, deaminated cytosine, and abasic sites, on the thermodynamics of …

Faculty Publications 2003, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 869 publications.

Detection And Mapping Of Quantitative Trait Loci That Determine Responsiveness, Janet L. Mueller, E. A. Ellenberger, Linda K. Vaughn, John K. Belknap, Raymond M. Quock

Biomedical Sciences Faculty Research and Publications

Exposure to 70% N₂O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N₂O. Offspring from the F₂ generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N₂O antinociception as determined by the acetic acid-induced abdominal constriction test. QTL analysis was then used to dissect this continuous trait distribution into component loci, and to map them to broad chromosomal regions. To this end, …

Visual Enhancing Of Tactile Perception In The Posterior Parietal Cortex, Tony Ro, Ruth Wallace, Judith Hagedorn, Alessandro Farnè, Elizabeth Pienkos

Publications and Research

The visual modality typically dominates over our other senses. Here we show that after inducing an extreme conflict in the left hand between vision of touch (present) and the feeling of touch (absent), sensitivity to touch increases for several minutes after the conflict. Transcranial magnetic stimulation of the posterior parietal cortex after this conflict not only eliminated the enduring visual enhancement of touch, but also impaired normal tactile perception. This latter finding demonstrates a direct role of the parietal lobe in modulating tactile perception as a result of the conflict between these senses. These results provide evidence for visual-to-tactile perceptual …

Target Selection For Antisense Oligonucleotide Induced Exon Skipping In The Dystrophin Gene, Stephen J. Errington

Theses: Doctorates and Masters

Duchene Muscular Dystrophy (DMD), and the milder allelic Becker muscular dystrophy (EMD), are X-linked recessive muscle wasting disorders characterised by mutations in the dystrophin gene. DMD occurs at a frequency of approximately 1 in 3500 male newborns and life expectancy is typically less than 30 years. Due to progressive muscle wasting, affected boys are restricted to a wheelchair by the age of 12 years. The most common cause of death is pneumonia, compounded by cardiac involvement. Mutations that disrupt the dystrophin reading frame, or prevent the synthesis of either terminus, preclude the synthesis of a fully functional dystrophin. The subsequent …

The Role Of Erp57 In Hras Intracellular Trafficking And Function., Jaime Lyn Parman

Electronic Theses and Dissertations

Ras is a central player in signal transduction that mediates cellular proliferation and differentiation. Recent evidence has shown that lipid and non-lipid modified domains participate in Ras traffic and that plasma membrane association is mediated by vectorial vesicular transport from the endomembrane system. ERp57, an ER chaperone, has been shown to specifically bind farnesylated Hras but not non-farnesylated Hras. The objective of this study was to determine if ERp57 participates in Ras trafficking and function. First, the effect of ERp57 knock down by siRNA technology on Hras function was studied; there was a reduction in ERp57 cellular levels that led …

Flavone: The Molecular And Mechanistic Study Of How A Simple Flavonoid Protects Dna From Oxidative Damage., Jennifer Dawn Dean

Electronic Theses and Dissertations

Dietary flavonoids are ubiquitous and are marketed as supplements. Characterized as antioxidants, they offer protection against a number of degenerative diseases. Flavonoid mechanics involve free radical scavenging, metal chelation, and substrate association. The skeletal structure of flavonoids is a fused ring system modified by hydroxyl, sugar, and carbohydrate additions. Flavone is a structurally simple flavonoid. Quercetin and its glycosidic analog rutin are complex structures. Using a DNA oxidation/cleavage assay, flavone reduces DNA nicking by 91%. Depending on the solvent system used, quercetin can either increase or decrease DNA oxidation. Rutin exhibits neither pro- nor antioxidant activity. The molecular interactions responsible …

Effect Of Background Synaptic Activity On Excitatory-Postsynaptic Potential-Spike Coupling, Veronika Zsiros

Theses and Dissertations (ETD)

Neurons receive large amount of synaptic inputs in vivo, which may impact the coupling between EPSPs and spikes. We mimicked the in vivo synaptic activity of the cell with the dynamic clamp system. We recorded from pyramidal cells in neocortical slices in vitro to investigate how timing and probability of spike generation in response to an EPSP is affected by background synaptic conductance under these conditions. We found that near threshold, background synaptic conductance improved the precision of spike timing by reducing the depolarization-related prolongation of the EPSP. In cells with ongoing spike activity and background synaptic conductances, an …

Protection Against Ischemia And Reperfusion Injury, Peter R. Oeltgen, Paul D. Bishop, Mark S. Kindy, Juan A. Sanchez

Molecular and Cellular Biochemistry Faculty Patents

A compound and method for using compound-D SEQ ID NO:1 to reduce injury associated with ischemia and reperfusion of mammalian organs such as the heart. The compound may be administered as part of a preconditioning strategy which reduces the extent of injury and improves organ function following cessation and restoration of blood flow. The compound may be used in preparation for planned ischemia or in a prophylactic manner in anticipation of further ischemic events.

Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas M. Ruden, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu

Biochemistry and Microbiology

Conrad Waddington published an influential model for evolution in his 1942 paper, Canalization of Development and Inheritance of Acquired Characters. In this classic, albeit controversial, paper, he proposed that an unknown mechanism exists that conceals phenotypic variation until the organism is stressed. Recent studies have proposed that the highly conserved chaperone Hsp90 could function as a “capacitor,” or an “adaptively inducible canalizer,” that masks silent phenotypic variation of either genetic or epigenetic origin. This review will discuss evidence for, and arguments against, the role of Hsp90 as a capacitor for morphological evolution, and as a key component of what …

Tomographic Reconstruction Of Treponemal Cytoplasmic Filaments Reveals Novel Bridging And Anchoring Components, Jacques Izard, Bruce F. Mcewen, Rita M. Barnard, Thomas Portuese, William A. Samsonoff, Ronald J. Limberger

Department of Food Science and Technology: Faculty Publications

An understanding of the involvement of bacterial cytoplasmic filaments in cell division requires the elucidation of the structural organization of those filamentous structures. Treponemal cytoplasmic filaments are composed of one protein, CfpA, and have been demonstrated to be involved in cell division. In this study, we used electron tomography to show that the filaments are part of a complex with a novel molecular organization that includes at least two distinct features decorating the filaments. One set of components appears to anchor the filaments to the cytoplasmic membrane. The other set of components appears to bridge the cytoplasmic filaments on the …

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …

Immortalized Epithelial Cells From Human Autosomal Dominant Polycystic Kidney Cysts, Mahmoud Loghman-Adham, Surya M. Nauli, Carlos E. Soto, Barbara Kariuki, Jing Zhou

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (ADPKD) is the result of mutations in one allele of the PKD1 or PKD2 genes, followed by "second hit" somatic mutations of the other allele in renal tubule cells. Continued proliferation of clonal cells originating from different nephron segments leads to cyst formation. In vitro studies of the mechanisms of cyst formation have been hampered by the scarcity of nephrectomy specimens and the limited life span of cyst-derived cells in primary culture. We describe the development of a series of immortalized epithelial cell lines from over 30 individual renal cysts obtained from 11 patients with …

Computational Models For Diffusion Of Second Messengers In Visual Transduction, Harihar Khanal

Publications

The process of phototransduction, whereby light is converted into an electrical response in retinal rod and cone photoreceptors, involves, as a crucial step, the diffusion of cytoplasmic signaling molecules, termed second messengers. A barrier to mathematical and computational modeling is the complex geometry of the rod outer segment which contains about 1000 thin discs. Most current investigations on the subject assume a well-stirred bulk aqueous environment thereby avoiding such geometrical complexity. We present theoretical and computational spatio-temporal models for phototransduction in vertebrate rod photoreceptors, which are pointwise in nature and thus take into account the complex geometry of the …

Use Of In Vivo-Induced Antigen Technology (Iviat) To Identify Genes Uniquely Expressed During Human Infection With Vibrio Cholerae, Long Hang, Manohar John, Muhammad Asaduzzaman, Emily A. Bridges, Cecily Vanderspurt, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

In vivo-induced antigen technology is a method to identify proteins expressed by pathogenic bacteria during human infection. Sera from 10 patients convalescing from cholera infection in Bangladesh were pooled, adsorbed against in vitro-grown El Tor Vibrio cholerae O1, and used to probe a genomic expression library in Escherichia coli constructed from El Tor V. cholerae O1 strain N16961. We identified 38 positive clones in the screen, encoding pili (PilA and TcpA), cell membrane proteins (PilQ, MshO, MshP, and CapK), methyl-accepting chemotaxis proteins, chemotaxis and motility proteins (CheA and CheR), a quorum-sensing protein (LuxP), and four hypothetical proteins. Analysis of immune …

Alginate Is Not A Significant Component Of The Extracellular Polysaccharide Matrix Of Pa14 And Pao1 Pseudomonas Aeruginosa Biofilms, Daniel J. Wozniak, Timna J. O. Wyckoff, Melissa Starkey, Rebecca Keyser, Parastoo Azadi, George A. O'Toole, Matthew R. Parsek

Dartmouth Scholarship

The bacterium Pseudomonas aeruginosa causes chronic respiratory infections in cystic fibrosis (CF) patients. Such infections are extremely difficult to control because the bacteria exhibit a biofilm-mode of growth, rendering P. aeruginosa resistant to antibiotics and phagocytic cells. During the course of infection, P. aeruginosa usually undergoes a phenotypic switch to a mucoid colony, which is characterized by the overproduction of the exopolysaccharide alginate. Alginate overproduction has been implicated in protecting P. aeruginosa from the harsh environment present in the CF lung, as well as facilitating its persistence as a biofilm by providing an extracellular matrix that promotes adherence. Because of …

Probucol Prevents Early Coronary Heart Disease And Death In The High-Density Lipoprotein Receptor Sr-Bi/Apolipoprotein E Double Knockout Mouse, Anne Braun, Songwen Zhang, Helena E. Miettinen, Shamsah Ebrahim, Teresa M. Holm, Eliza Vasile, Mark J. Post

Dartmouth Scholarship

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment …

Effects Of Ethanol On Anti-Saccade Task Performance., Sarah A Khan, Kristen Ford, Brian Timney, Stefan Everling

Brain and Mind Institute Researchers' Publications

It has been shown that saccade-related neurons in the superior colliculus (SC) display an increased level of prestimulus activity and a higher stimulus-related burst in action potentials preceding direction errors in the anti-saccade task compared with correct anti-saccades. From this, it has been hypothesized that errors occur when the incoming visual signal in the SC passes a threshold and triggers a reflexive saccade. This hypothesis predicts that an attenuated visual signal will reduce the number of direction errors. Since ethanol has been shown to have a suppressive effect on cortical visual event-related potentials (ERPs), the purpose of the present study …

Hdl-Associated Estradiol Stimulates Endothelial No Synthase And Vasodilation In An Sr-Bi–Dependent Manner, Ming Gong, Melinda E. Wilson, Thomas Kelly, Wen Su, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Theresa Guerin, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Eric J. Smart

Pediatrics Faculty Publications

Cardiovascular diseases remain the leading cause of death in the United States. Two factors associated with a decreased risk of developing cardiovascular disease are elevated HDL levels and sex — specifically, a decreased risk is found in premenopausal women. HDL and estrogen stimulate eNOS and the production of nitric oxide, which has numerous protective effects in the vascular system including vasodilation, antiadhesion, and anti-inflammatory effects. We tested the hypothesis that HDL binds to its receptor, scavenger receptor class B type I (SR-BI), and delivers estrogen to eNOS, thereby stimulating the enzyme. HDL isolated from women stimulated eNOS, whereas HDL isolated …

Seventeen Amino Acid Peptide (Peptide P) For Treating Ischemia And Reperfusion Injury, Peter R. Oeltgen, Mark S. Kindy

Molecular and Cellular Biochemistry Faculty Patents

Peptide P, having the amino acid sequence Tyr-D-Ala-Phe-Ala-Asp-Val-Ala-Ser-Thr-Ile-Gly-Asp-Phe-Phe-His-Ser-Ile-NH2, is useful to treat ischemia.

Expression Of Glutathione-S-Transferase Mu 1 (Gstm1) And Glutathione-S-Transferase Theta 1 (Gstt1) In Patients With Aplastic Anemia And Myelodysplastic Syndromes, Aaron Conrad Spivey

Theses and Dissertations in Biomedical Sciences

Aplastic Anemia is a disorder of the hematopoietic bone marrow stem cells that is frequently associated with drug or chemical exposures. Reduced ability to detoxify drugs or chemicals may result in an increased risk of disease. Glutathione S-transferases are Phase II enzymes, which help detoxify xenobiotics. Many patients who have developed aplastic anemia and myelodysplastic syndrome have the null genotype for GSTMI and/or GSTTI. For patients with GSTMI and GSTTI positive genotypes, non-expression of these enzymes may cause an increased risk in developing aplastic anemia or myelodysplastic syndrome. To test whether genotype positive patients have GSTMI or GSTTI null …

An Evaluation Of Topical And Local Anesthesia In Phacoemulsification, Z Rizvi, T Rehman, S Malik, A Qureshi, L Paul, K Qureshi, S Memon, S Rafi, A Ali

Medical College Documents

Objective: To assess the comparative efficacy of topical and local anesthesia in phacoemulsification.MATERIAL AND Methods: The medical records of 186 men and women between the ages of 45-85 years, who underwent elective cataract surgery by phacoemulsification technique, under the care of one surgeon, over a period of one year, from March 1999-March 2000 were reviewed.Results: Of 186 patients who underwent small incision, self-healing phacoemulsification cataract surgery, 124 received topical and 62 local anesthesia. The most common cataract types were nuclear sclerosis. The duration of surgery with topical anesthesia was shorter. Sutures and eye padding were more frequently applied for procedures …

Role Of Proapoptotic Bax In Propagation Of Chlamydia Muridarum (The Mouse Pneumonitis Strain Of Chlamydia Trachomatis) And The Host Inflammatory Response, Jean-Luc Perfettini, David M. Ojcius, Charles W. Andrews Jr., Stanley J. Korsmeyer, Roger G. Rank, Toni Darville

All Dugoni School of Dentistry Faculty Articles

The BCL-2 family member BAX plays a critical role in regulating apoptosis. Surprisingly, bax-deficient mice display limited phenotypic abnormalities. Here we investigate the effect of BAX on infection by the sexually transmitted pathogen,Chlamydia muridarum (the mouse pneumonitis strain ofChlamydia trachomatis). Bax −/−cells are relatively resistant to Chlamydia-induced apoptosis, and fewer bacteria are recovered after two infection cycles from Bax −/− cells than from wild-type cells. These results suggest that BAX-dependent apoptosis may be used to initiate a new round of infection, most likely by releasingChlamydia-containing apoptotic bodies from infected cells that could be internalized by neighboring uninfected cells. Nonetheless, infected …