Digital Commons Network^™

The Virulence Activator Apha Links Quorum Sensing To Pathogenesis And Physiology In Vibrio Cholerae By Repressing The Expression Of A Penicillin Amidase Gene On The Small Chromosome, Gabriela Kovacikova, Wei Lin, Karen Skorupski

Dartmouth Scholarship

Activation of the tcpPH promoter on the Vibrio pathogenicity island by AphA and AphB initiates the Vibrio cholerae virulence cascade and is regulated by quorum sensing through the repressive action of HapR on aphA expression. To further understand how the chromosomally encoded AphA protein activates tcpPH expression, site-directed mutagenesis was used to identify the base pairs critical for AphA binding and transcriptional activation. This analysis revealed a region of partial dyad symmetry, TATGCA-N6-TNCNNA, that is important for both of these activities. Searching the V. cholerae genome for this binding site permitted the identification of a second one upstream of a …

Genetic Polymorphisms Of The Interleukin-1 Gene And Early Marginal Bone Loss Around Endosseous Dental Implants, Hitomi Shimpuku, Yasuhiro Nosaka, Tatsuya Kawamura, Yoichi Tachi, Mitsuko Shinohara

Faculty, Staff and Student Publications

Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery …

Characterization Of Mutations And Loss Of Heterozygosity Of P53 And K-Ras2 In Pancreatic Cancer Cell Lines By Immobilized Polymerase Chain Reaction, James Butz, Eric Wickstrom, Jeremy Edwards

Department of Biochemistry and Molecular Biology Faculty Papers

Background

The identification of known mutations in a cell population is important for clinical applications and basic cancer research. In this work an immobilized form of the polymerase chain reaction, referred to as polony technology, was used to detect mutations as well as gene deletions, resulting in loss of heterozygosity (LOH), in cancer cell lines. Specifically, the mutational hotspots in p53, namely codons 175, 245, 248, 249, 273, and 282, and K-ras2, codons 12, 13 and 61, were genotyped in the pancreatic cell line, Panc-1. In addition LOH analysis was also performed for these same two genes in Panc-1 by …

Gaze-Centered Updating Of Visual Space In Human Parietal Cortex., W Pieter Medendorp, Herbert C Goltz, Tutis Vilis, J Douglas Crawford

Brain and Mind Institute Researchers' Publications

Single-unit recordings have identified a region in the posterior parietal cortex (PPC) of the monkey that represents and updates visual space in a gaze-centered frame. Here, using event-related functional magnetic resonance imaging, we identified an analogous bilateral region in the human PPC that shows contralateral topography for memory-guided eye movements and arm movements. Furthermore, when eye movements reversed the remembered horizontal target location relative to the gaze fixation point, this PPC region exchanged activity across the two cortical lobules. This shows that the human PPC dynamically updates the spatial goals for action in a gaze-centered frame.

Crystal Structure Of The Sars Protein From Staphylococcus Aureus, Ronggui Li, Adhar C. Manna, Shaodong Dai, Ambrose L. Cheung, Gongyi Zhang

Dartmouth Scholarship

The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sarA and agr). One of these determinants, protein A (spa), is activated by sarS, which encodes a 250-residue DNA-binding protein. Genetic analysis indicated that the agr locus likely mediates spa repression by suppressing the transcription of sarS. Contrary to SarA and SarR, which require homodimer formation for proper function, SarS is unusual within the SarA protein family in that it contains two homologous halves, with each half sharing sequence similarity to SarA and SarR. Here we report the 2.2 Å …

Neuronal Cell Model And Methods Of Use Thereof, Craig S. Miller, Robert J. Jacob, Robert J. Danaher

Microbiology, Immunology and Molecular Genetics Faculty Patents

We previously described a novel in vitro model of a non-productive herpes simplex virus type 1 (HSV-1) infection in neurally-differentiated (ND)-PC12 cells that allows for inducible virus replication upon forskolin and heat stress (HS) treatment. In this research, we further characterized the model with respect to HSV-2 strain 333. We found that: (i) ND-PC12 cells are non-permissive to HSV-2 replication; (ii) HSV-2 can establish a quiescent infection, like HSV-1, in ND-PC12 cells with the transient use of acycloguanosine (ACV); however unlike HSV-1, anti-viral conditions are not obligatory to establish and maintain a quiescent state; (iii) the quiescent state is maintained …

Interaction Between Adrenergic And Nitric Oxide-Releasing Nerves In Cerebral Arteries, Emmanuel Ngu Mbaku

Loma Linda University Electronic Theses, Dissertations & Projects

Of all body tissues, the brain is the least tolerant of ischemia so much that interruption of cerebral blood flow by 5 sec can cause syncope, with irreversible tissue damage if the ischemia last a few minutes. In this respect, the body has an imperative duty of ensuring constant and adequate blood supply to the brain. It does so through a series of intrinsic and extrinsic control factors of which adrenergic and nitric oxide-releasing nerves are components. My research examined the interaction between these two nerve-types with emphasis on the mechanisms involved as well as on changes in their functions …

Water Quality Assessment In Cypress Creek Nature Preserve, Jason Flora

Masters Theses & Specialist Projects

Swamps are unique ecological communities that provide many valuable ecosystem services. In Kentucky, however, many swamps were altered by cypress removal and land development in their watersheds. Cypress Creek Swamp, which lies near Paducah in western Kentucky, is a good example of a swamp whose ecological integrity may be threatened by past and current nearby land use practices. This study was conducted to assess the water quality and macro- and microinvertebrate communities in the swamp. Three sites were monitored for temperature, dissolved oxygen, pH, specific conductivity, depth, phosphorus measured as orthophosphate, nitrite (NO2") and nitrate (NO3", NOx collectively), and ammonia …

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 …

Lysosomal Membrane Permeabilization Induces Cell Death In A Mitochondrion-Dependent Fashion, Patricia Boya, Karine Andreau, Delphine Poncet, Naoufal Zamzami, Jean-Luc Perfettini, Didier Metivier, David M. Ojcius, Marja Jäättelä, Guido Kroemer

All Dugoni School of Dentistry Faculty Articles

A number of diseases are due to lysosomal destabilization, which results in damaging cell loss. To investigate the mechanisms of lysosomal cell death, we characterized the cytotoxic action of two widely used quinolone antibiotics: ciprofloxacin (CPX) or norfloxacin (NFX). CPX or NFX plus UV light (NFX*) induce lysosomal membrane permeabilization (LMP), as detected by the release of cathepsins from lysosomes. Inhibition of the lysosomal accumulation of CPX or NFX suppresses their capacity to induce LMP and to kill cells. CPX- or NFX-triggered LMP results in caspase-independent cell death, with hallmarks of apoptosis such as chromatin condensation and phosphatidylserine exposure on …

Alpha-Toxin Is Required For Biofilm Formation By Staphylococcus Aureus, Nicky C. Caiazza, George A. O'Toole

Dartmouth Scholarship

Staphylococcus aureus is a common pathogen associated with nosocomial infections. It can persist in clinical settings and gain increased resistance to antimicrobial agents through biofilm formation. We have found that alpha-toxin, a secreted, multimeric, hemolytic toxin encoded by the hla gene, plays an integral role in biofilm formation. The hla mutant was unable to fully colonize plastic surfaces under both static and flow conditions. Based on microscopy studies, we propose that alpha-hemolysin is required for cell-to-cell interactions during biofilm formation.

Method For Enhancing Protective Cellular Responses To Genotoxic Stress In Skin, Elaine L. Jacobson, Myron Jacobson

Graduate Center for Nutritional Sciences Faculty Patents

The present invention is directed to methods of using pro-NAD agents capable of enhancing the dermal and epidermal skin cell NAD content. These pro-NAD agents may be administered topically, orally, or parenterally to enhance DNA repair and other protective responses to DNA damage. The invention further relates to pharmaceutical compositions comprising pro-NAD agents that effectively elevate intracellular NAD content. Finally, the invention relates to the method of using the pro-NAD agents to treat disorders such as sunburn and other skin deterioration that results from DNA damage in skin cells.

Hierarchical Processing In Spoken Language Comprehension., Matthew H Davis, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Understanding spoken language requires a complex series of processing stages to translate speech sounds into meaning. In this study, we use functional magnetic resonance imaging to explore the brain regions that are involved in spoken language comprehension, fractionating this system into sound-based and more abstract higher-level processes. We distorted English sentences in three acoustically different ways, applying each distortion to varying degrees to produce a range of intelligibility (quantified as the number of words that could be reported) and collected whole-brain echo-planar imaging data from 12 listeners using sparse imaging. The blood oxygenation level-dependent signal correlated with intelligibility along the …

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 …

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 …

Gene Therapy For Pediatric Cancer: State Of The Art And Future Perspectives, Malcolm Brenner

Faculty, Staff and Students Publications

While modern treatments have led to a dramatic improvement in survival for pediatric malignancy, toxicities are high and a significant proportion of patients remain resistant. Gene transfer offers the prospect of highly specific therapies for childhood cancer. "Corrective" genes may be transferred to overcome the genetic abnormalities present in the precancerous cell. Alternatively, genes can be introduced to render the malignant cell sensitive to therapeutic drugs. The tumor can also be attacked by decreasing its blood supply with genes that inhibit vascular growth. Another possible approach is to modify normal tissues with genes that make them more resistant to conventional …

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 …

High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

Background

d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …

Characterization Of A Gene Encoding Two Isoforms Of A Mitochondrial Protein Upregulated By Cyclosporin A In Activated T Cells, Laurent Mascarell, Rodolphe Auger, Andres Alcover, David M. Ojcius, Thomas Jungas, Veronique Cadet-Daniel, Jean M. Kanellopoulos, Paolo Truffa-Bacchi

All Dugoni School of Dentistry Faculty Articles

Cyclosporin A (CSA) is an immunosuppressor used in organ transplantation. A recent proteomic analysis has revealed that activation of T cells in the presence of CSA induces the synthesis of hundreds of new proteins. Here we used representational difference analysis to characterize some of the corresponding induced genes. After cDNA bank screening we focused on one of these genes, which we named CSA-conditional, T cell activation-dependent (CSTAD) gene. This gene produces two mRNAs resulting from alternative splicing events. They encode two proteins of 104 and 141 amino acids, CSTADp-S and CSTADp-L, for the short and long forms, respectively. FK506 had …

Male Breast Cancer, N Kayani, M N. Khan, Y Bhurgri, S Gill, M I. Nasir, T Siddiqui

Department of Pathology and Laboratory Medicine

Objective: To review cases of male breast cancer.
Settings: Histopathology Section, Department of Pathology, The Aga Khan University, Karachi.
Method: Fifty one cases of male breast cancer specimens, received during a period of 10 years, routinely processed and stained with Haematoxylin and Eosin were analyzed. Special stains and Immunohistochemistry were used in difficult cases.
Results: Male breast cancer affected individuals in the sixth and seventh decades of life with a mean age of 56.2 years. Infiltrating ductal carcinoma (IDC) was the predominant type. Skin involvement was seen in 27.45% of the cases. Breast lump was the most common presenting symptom …

Hierarchy Of Protein Assembly At The Vertex Ring Domain For Yeast Vacuole Docking And Fusion, Li Wang, Alexey J. Merz, Kevin M. Collins, William Wickner

Dartmouth Scholarship

Vacuole tethering, docking, and fusion proteins assemble into a “vertex ring” around the apposed membranes of tethered vacuoles before catalyzing fusion. Inhibitors of the fusion reaction selectively interrupt protein assembly into the vertex ring, establishing a causal assembly hierarchy: (a) The Rab GTPase Ypt7p mediates vacuole tethering and forms the initial vertex ring, independent of t-SNAREs or actin; (b) F-actin disassembly and GTP-bound Ypt7p direct the localization of other fusion factors; (c) The t-SNAREs Vam3p and Vam7p regulate each other’s vertex enrichment, but do not affect Ypt7p localization. The v-SNARE Vti1p is enriched at vertices by a distinct pathway that …

Hiv Protease Inhibitors Promote Atherosclerotic Lesion Formation Independent Of Dyslipidemia By Increasing Cd36-Dependent Cholesteryl Ester Accumulation In Macrophages, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Richard N. Greenberg, Theresa Guerin, David Meade, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Melinda E. Wilson, Eric J. Smart

Physiology Faculty Publications

Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor–dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor–induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and …

Rhamnolipid Surfactant Production Affects Biofilm Architecture In Pseudomonas Aeruginosa Pao1, Mary E. Davey, Nicky C. Caiazza, George A. O'Toole

Dartmouth Scholarship

In response to certain environmental signals, bacteria will differentiate from an independent free-living mode of growth and take up an interdependent surface-attached existence. These surface-attached microbial communities are known as biofilms. In flowing systems where nutrients are available, biofilms can develop into elaborate three-dimensional structures. The development of biofilm architecture, particularly the spatial arrangement of colonies within the matrix and the open areas surrounding the colonies, is thought to be fundamental to the function of these complex communities. Here we report a new role for rhamnolipid surfactants produced by the opportunistic pathogen Pseudomonas aeruginosa in the maintenance of biofilm architecture. …

Monoclonal Antibody 1a7 And Use For The Treatment Of Melanoma And Small Cell Carcinoma, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention relates to monoclonal antibody 1A7. This is an anti-idiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered …

Vinpocetine For Cognitive Impairment And Dementia, Peter J. Whitehouse

Faculty Scholarship

Background: Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear. Objectives: To assess the efficacy and safety of vinpocetine in the treatment …

Equilibrative Nucleoside Transporter Family Members From Leishmania Donovani Are Electrogenic Proton Symporters, Alex Stein, Gayatri Vaseduvan, Nicola S. Carter, Buddy Ullman, Scott M. Landfear, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Leishmania donovani express two members of the equilibrative nucleoside transporter family; LdNT1 encoded by two closely related and linked genes, LdNT1.1 and LdNT1.2, that transport adenosine and pyrimidine nucleosides and LdNT2 that transports inosine and guanosine exclusively. LdNT1.1, LdNT1.2, and LdNT2 have been expressed in Xenopus laevis oocytes and found to be electrogenic in the presence of nucleoside ligands for which they mediate transport. Further analysis revealed that ligand uptake and transport currents through LdNT1-type transporters are proton-dependent. In addition to the flux of protons that is coupled to the transport reaction, LdNT1 transporters mediate a variable constitutive proton …

The Ca2+ Dynamics Of Isolated Mouse Β-Cells And Islets: Implications For Mathematical Models, Min Zhang, Paula Goforth, Richard Bertram, Arthur Sherman, Leslie S. Satin

Pharmacology and Toxicology Publications

ABSTRACT

[Ca²⁺]_i and electrical activity were compared in isolated β-cells and islets using standard techniques. In islets, raising glucose caused a decrease in [Ca²⁺]_i followed by a plateau and then fast (2–3 min⁻¹), slow (0.2–0.8 min⁻¹), or a mixture of fast and slow [Ca²⁺]_i oscillations. In β-cells, glucose transiently decreased and then increased [Ca²⁺]_i, but no islet-like oscillations occurred. Simultaneous recordings of [Ca²⁺]_i and electrical activity suggested that differences in [Ca²⁺]_i signaling are due to …

The Role Of Oxidative Stress In Alzheimer's Disease, Robin Petroze

Kaleidoscope

Over four million individuals in the United States currently suffer from Alzheimer's disease (AD), a devastating disorder of progressive dementia. Within the next several decades, AD is expected to affect over 22 million people globally. AD can only be definitively diagnosed by postmortem examination. Thus, investigation into the specific pathogenesis of neuronal degeneration and death in AD on a biochemical level is essential for both earlier diagnosis and potential treatment and prevention options. Overproduction of amyloid [3-peptide (A[3) in the brain leads to both free radical oxidative stress and toxicity to neurons in AD. My undergraduate biochemical studies with regard …

President's Message

Journal of the South Carolina Academy of Science

No abstract provided.

Par Mediation Of Thrombin-Induced Effects On Motoneurons, Nadim Salman, Drew Watkins, Kate Hamel, Lakisha Gadsden, Sarah Funderburk, Victoria Turgeon

Journal of the South Carolina Academy of Science

No abstract provided.