Medicine and Health Sciences Commons^™

Copper Chelation Represses The Vascular Response To Injury, Lazar Mandinov, Anna Mandinova, Stanimir Kyurkchiev, Dobroslav Kyurkchiev, Ivan Kehayov, Vihren Kolev, Raffaella Soldi, Cinzia Bagala, Ebo D. De Muinck, Volkhard Lindner, Mark J. Post, Michael Simons

Dartmouth Scholarship

The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu2+-binding proteins IL-1alpha and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu2+ to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo, we examined the ability of Cu2+ chelation to repress neointimal thickening in response to injury. We observed that the oral administration of …

Vam10p Defines A Sec18p-Independent Step Of Priming That Allows Yeast Vacuole Tethering, Masashi Kato, William Wickner

Dartmouth Scholarship

YOR068c, termed VAM10 (altered vacuole morphology), lies within the VPS5 gene on the opposite DNA strand. VAM10 deletion causes vacuole fragmentation in vivo. The in vitro fusion of purified yeast vacuoles is stimulated by recombinant Vam10p and blocked by antibody to Vam10p. Vam10p acts early in the priming stage of fusion, independent of Sec18p. After priming, recombinant Vam10p will not stimulate fusion and anti-Vam10p antibodies will not inhibit; Vam10p provides a functional marker for this Sec18p-independent priming step. Pure Vam10p restores normal, Ypt7p-dependent tethering to vacuoles from a vam10Δ strain.

Rhythmic Binding Of A White Collar-Containing Complex To The Frequency Promoter Is Inhibited By Frequency, Allan C. Froehlich, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

The biological clock of Neurospora crassa includes interconnected transcriptional and translational feedback loops that cause both the transcript and protein encoded by the frequency gene (frq) to undergo the robust daily oscillations in abundance, which are essential for clock function. To understand better the mechanism generating rhythmic frq transcript, reporter constructs were used to show that the oscillation in frq message is transcriptionally regulated, and a single cis-acting element in the frq promoter, the Clock Box (C box), is both necessary and sufficient for this rhythmic transcription. Nuclear protein extracts used in binding assays revealed that a White Collar (WC)-1- …

Characterization Of Sympathetic Ganglion Sensitivity To Substance P In A Genetic And A Non-Genetic Rat Model Of Hypertension., John Daniel Tompkins

Electronic Theses and Dissertations

Intravenous injection of substance P (SP) stimulates sympathetic ganglia to evoke a greater increase in renal sympathetic nerve activity, heart rate (HR) and blood pressure (BP) in hypertensive than normotensive rats due to upregulation of the NK₁ receptor. These experiments were designed to determine the cellular basis for the enhanced ganglionic responsiveness to NK₁ agonists in spontaneously hypertensive rats (SHR) in comparison to their normotensive counterparts, Wistar-Kyoto rats (WKY). Studies were also conducted to determine whether the increased ganglion responsiveness to SP in SHR is causally related to the increased BP or is a unique characteristic of this …

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 …

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 …

Plasma Total Homocysteine And The Effect Of B-Group Vitmains. Current Knowledge And Future Directions In Assessment For Cardiovascular Diseases Among U.S. Cardiovascular Specialists, Salam F. Sunna

All-Inclusive List of Electronic Theses and Dissertations

Cardiovascular disease remains the major cause of morbidity and mortality in the United States claiming the lives of over 40% of the nearly 2.4 million Americans who die each year. Recent studies have shown that elevated homocysteine in the blood is related to a higher risk of coronary heart disease, peripheral vascular disease and stroke independent of other classical cardiovascular disease risk factors. The aim of this study is to determine the general awareness and acceptance of U.S. cardiovascular specialists of the homocysteine theory, the criteria used for ordering a homocysteine test, the frequency physicians refer patients to dietitians for …

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.

Protection Of Pifithrin-Α And Melatonin Against Doxorubicin-Induced Cardiotoxicity., Xuwan Liu

Electronic Theses and Dissertations

The current studies were designed to explore the protective effects of pifithrin-α and melatonin against doxorubicin-induced cardiotoxicity. Doxorubicin was injected at a dose of 22.5 mg/kg (i.p.) in mice to induce cardiotoxic effects. Meanwhile, doxorubicin caused a significant increase of cardiac cell apoptosis following injection (14.2 ± 1.1% for doxorubicin-5 d vs. 1.8 ± 0.12% for control, P < 0.01). Ribonuclease protection assays and Western blot analyses revealed that doxorubicin upregulated the p53-dependent genes Bax, BclxL, and MDM2 at least 2-fold. p53 was phosphorylated at Ser 15 in mouse hearts 1 h following doxorubicin injection, and p38 and ERK1/2 MAPKs mediated the phosphorylation of p53. In addition, caspases-3 and -9 were activated 24 h after doxorubicin injection. A p53 inhibitor, pifithrin-α, inhibited doxorubicin-induced apoptosis when administered at a dose of 2.2 mg/kg. Pifithrin-α abolished p53 transactivation activity, but did not influence doxorubicin-induced phosphorylation at Ser 15. By effectively inhibiting the expression of p53-dependent genes, pifithrin-α blocked doxorubicin-induced activation of caspases-3 and -9, thereby preventing cardiac apoptosis. In addition, pifithrin-α attenuated doxorubicin-induced structural and functional damages, without diminishing its anti-tumor efficacy on p53-null PC-3 cancer cells. The protective effects of melatonin and its metabolite 6-hydroxymelatonin on doxorubicin-induced cardiac dysfunction were evaluated in an isolated perfused mouse hearts and in vivo doxorubicin-treated mice. While perfusion of mouse hearts with 5 μM doxorubicin for 60 min resulted in a 50% suppression of HRxLVDP and a 50% reduction of coronary flow, pre-exposure of hearts to 1 μM melatonin or 6-hydroxymelatonin eased the cardiac …

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 …

Mammalian Erv46 Localizes To The Endoplasmic Reticulum–Golgi Intermediate Compartment And To Cis-Golgi Cisternae, Lelio Orci, Mariella Ravazzola, Gary J. Mack, Charles Barlowe, Stefan Otte

Dartmouth Scholarship

Yeast endoplasmic reticulum (ER) vesicle protein Erv46p is a novel membrane protein involved in transport through the early secretory pathway. Investigation of mammalian Erv46 (mErv46) reveals that it is broadly expressed in tissues and protein-secreting cells. By immunofluorescence microscopy, mErv46 displays a crescent-shaped perinuclear staining pattern that is characteristic of the Golgi complex. Quantitative immunoelectron microscopy indicates that mErv46 is restricted to the cis face of the Golgi apparatus and to vesicular tubular structures between the transitional ER and cis-Golgi. Minor amounts of mErv46 reside in ER membranes and later Golgi cisternae. On Brefeldin A treatment, mErv46 redistributes to punctate …

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.

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 …

Cell-Cycle Regulatory Proteins In Podocyte Cell In Idiopathic Nephrotic Syndrome Of Childhood., Tarak Srivastava, Robert E. Garola, J M. Whiting, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The podocyte cell is believed to play an important role in idiopathic nephrotic syndrome (INS) of childhood. In adults with cellular and collapsing focal segmental glomerulosclerosis (FSGS), the expression of cell-cycle regulatory proteins such as p27, p57, and cyclin D is decreased and expression of cyclin A, Ki-67, and p21 is observed in podocyte cells suggestive of a dysregulated podocyte phenotype. We investigated for alterations in the expression of cyclin kinase inhibitors, p27, p57, p21, and cyclins D and A in the podocyte cell of children with INS.

METHODS: Forty-two kidney biopsies were investigated; 14 with minimal-change disease (MCD), …

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 …

Human Acyl-Coenzyme A:Cholesterol Acyltransferase Expressed In Chinese Hamster Ovary Cells: Membrane Topology And Active Site Location, Song Lin, Xiaohui Lu, Catherine C.Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Acyl-CoA:cholesterol acyltransferase (ACAT) is a membrane-bound enzyme that produces cholesteryl esters intracellularly. Two ACAT genes (ACAT1 and ACAT2) have been identified. The expression of ACAT1 is ubiquitous, whereas that of ACAT2 is tissue restricted. Previous research indicates that ACAT1 may contain seven transmembrane domains (TMDs). To study ACAT2 topology, we inserted two different antigenic tags (hemagglutinin, monoclonal antibody Mab1) at various hydrophilic regions flanking each of its predicted TMDs, and expressed the recombinant proteins in mutant Chinese hamster ovary cells lacking endogenous ACAT. Each tagged ACAT2 was expressed in the endoplasmic reticulum as a single undegraded protein band …

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 …

Transfection Of Il-10 Expression Vectors Into Endothelial Cultures Attenuates Alpha4beta7-Dependent Lymphocyte Adhesion Mediated By Madcam-1., Makoto Sasaki, Paul Jordan, Jeff Houghton, Xianmin Meng, Makoto Itoh, Takashi Joh, J Steven Alexander

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression …

Promoters Of The Murine Embryonic Β-Like Globin Genes Ey And Βh1 Do Not Compete For Interaction With The Β-Globin Locus Control Region, Xiao Hu, Michael Bulger, Julia N. Roach, Susan K. Eszterhas, Emmanuel Olivier, Eric Bouhassira, Mark Groudine, Steven Fiering

Dartmouth Scholarship

Mammalian β-globin loci contain multiple β-like genes that are expressed at different times during development. The murine β-globin locus contains two genes expressed during the embryo stage, Ey and βh1, and two genes expressed at both the fetal and postnatal stages, β-major and β-minor. Studies of transgenic human β-like globin loci in mice have suggested that expression of one gene at the locus will suppress expression of other genes at the locus. To test this hypothesis we produced mouse lines with deletions of either the Ey or βh1 promoter in the endogenous murine β-globin locus. Promoter deletion eliminated expression of …

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 …

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. …

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 …

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 …