Digital Commons Network^™

Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron

Biochemistry and Microbiology

Background: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammmary adenocarcinoma cells in C3H/HeJ mice.

Materials and Methods: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 …

Expression Of Tumor-Associated Glycoprotein-72 (Tag-72) Antigen In Human Prostatic Adenocarcinomas., Dev Karan, Sonny L. Johansson, Ming-Fong Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Tumor-specific antigens are usually defined by monoclonal antibodies (MAbs) and can play critical roles in the diagnosis and therapy of carcinomas. Despite advances in the understanding of the molecular genetics of human prostate carcinomas, therapeutic approaches require that tumor-specific markers, preferably on the cell surface, should be defined. In this study, we examined the expression of an oncofetal antigen tumor-associated glycoprotein-72 (TAG-72) in prostatic adenocarcinomas with a Gleason grade of six or higher. Using a second generation MAb CC49 against TAG-72, immunoreactivity was detected in 88% (29/33) of the prostatic cancer tissues. Occasionally, the benign epithelium showed a very faint …

Secondary Level Screening Of Chlamydomonas Reinhardtii Mutants Defective In Circadian Gene Expression, Mingya Huang

Masters Theses & Specialist Projects

To elucidate the signal transduction chain mediating circadian clock control, this work focuses on the isolation of Chlamydomonas reinhardtii mutants which are defective in circadian gene expression. In a previous study, the reporter gene ARS2 encoding the arylsulfatase enzyme was fused to the promoter of the circadian-regulated CABII-1 gene and transformed into the Chlamydomonas nucleus. The ble marker was introduced into the genome of this transformant via insertional mutagenesis to generate mutants defective in circadian CABII-1 expression. Potential mutants were selected based on aberrant single-point accumulative arylsulfatase activity. In this study, the arylsulfatase activity over the entire growth cycle was …

A Novel Strategy Utilizing Co-Expression Of Murine Il-12 And Antisense Tgf-Pl Against H238 Tumor Formation, Craig A. Seheult

Loma Linda University Electronic Theses, Dissertations & Projects

Cytokines have a profound effect on immune modulation, thus playing a significant role in cancer gene therapy. A variety of human carcinomas secrete transforming growth factor-beta (TGF-β), a cytokine with potent immunosuppressive properties. Suppressing TGF-β could be a key to successfully combating malignancies, such as gliomas, mammary, and colon cancers, that over-express TGF-β. Conversely, interleukin-12 (IL-12) is a potent immunostimulatory cytokine capable of regulating T and NK cell-mediated cytotoxic responses (Trinchieri, 1994) during an anti-tumor response. Activation of the immune system with such immunostimulatory cytokines renders it inert to the suppressive effects of TGF-β. To better understand these processes our …

Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung

Dartmouth Scholarship

In searching the Staphylococcus aureus genome, we found several homologs to SarA. One of these genes, sarT, codes for a basic protein with 118 residues and a predicted molecular size of 16,096 Da. Northern blot analysis revealed that the expression of sarT was repressed by sarA and agr. An insertion sarT mutant generated in S. aureus RN6390 and 8325-4 backgrounds revealed minimal effect on the expression of sarR and sarA. The RNAIII level was notably increased in the sarT mutant, particularly in postexponential-phase cells, while the augmentative effect on RNAII was less. SarT repressed the expression of alpha-hemolysin, as determined …

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

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention provides, inter alia, a PC12 cell quiescently infected with a neurotropic virus. Preferred quiescently-infected neural cells are those wherein the neurotropic virus is a neurotropic herpes virus. Methods related to these and other materials are also provided.

The Toxoplasma Gondii Protein Rop2 Mediates Host Organelle Association With The Parasitophorous Vacuole Membrane, Anthony P. Sinai, Keith A. Joiner

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH₂-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is …

Guanylyl Cyclase C Agonists Regulate Progression Through The Cell Cycle Of Human Colon Carcinoma Cells., Giovanni Mario Pitari, M D Di Guglielmo, J Park, S Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, …

Tetrafluoroazidoaniline And Method Of Making And Using The Same, Hans Peter Spielmann, Kareem A.H. Chehade

Molecular and Cellular Biochemistry Faculty Patents

The invention is directed to a novel compounds comprising 4-azidotetrafluoroaniline and the alkyl, acyl and sulfonamide derivatives thereof and to methods of making and using the same. The novel compounds are useful as a photoaffinity probe to study protein structure and function. Two methods for preparing 4-azidotetrafluoroaniline are disclosed, each employing a stable carbamate intermediate from which the 4-azidotetrafluoroaniline is derived.

Crystal Structure Of The Sarr Protein From Staphylococcus Aureus, Yingfang Liu, Adhar Manna, Ronggui Li, Wesley E. Martin, Robert C. Murphy, 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). The sar (Staphylococcus accessory regulator) locus is composed of three overlapping transcripts (sarA P1, P3, and P2, transcripts initiated from the P1, P3, and P2 promoters, respectively), all encoding the 124-aa SarA protein. The level of SarA, the major regulatory protein, is partially controlled by the differential activation of the sarA promoters. We previously partially purified a 13.6-kDa protein, designated SarR, that binds to the sarA promoter region to down-modulate sarA transcription from the P1 promoter and subsequently SarA expression. SarR shares …

Marek's Disease Virus (Mdv) Encodes An Interleukin-8 Homolog (Vil-8): Characterization Of The Vil-8 Protein And A Vil-8 Deletion Mutant Mdv, Mark S. Parcells, Su-Fang Lin, Robert L. Dienglewicz, Vladimir Majerciak, Dan R. Robinson, Hua-Chien Chen, Zining Wu, George R. Dubyak, Peter Brunovskis, Henry D. Hunt

Dartmouth Scholarship

Chemokines induce chemotaxis, cell migration, and inflammatory responses. We report the identification of an interleukin-8 (IL-8) homolog, termed vIL-8, encoded within the genome of Marek's disease virus (MDV). The 134-amino-acid vIL-8 shares closest homology to mammalian and avian IL-8, molecules representing the prototype CXC chemokine. The gene for vIL-8 consists of three exons which map to the BamHI-L fragment within the repeats flanking the unique long region of the MDV genome. A 0.7-kb transcript encoding vIL-8 was detected in an n-butyrate-treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is essentially abolished by cycloheximide and herpesvirus DNA polymerase inhibitor phosphonoacetate, indicating …

Cocaine Induces Apoptosis In Coronary Artery Endothelial Cells: Cellular And Molecular Mechanisms, Jiale He

Loma Linda University Electronic Theses, Dissertations & Projects

Cocaine abuse has been associated with numerous cardiovascular consequences, such as depressed myocardial contractility, elevated blood pressure, coronary artery vasoconstriction, and myocardial ischemia and infarction. The multifactorial effects of cocaine often contribute to its sympathomimetic function. However, the direct cytotoxic effects of cocaine on the cardiovascular system, especially vascular endothelium, and the cellular and molecular mechanisms remain unknown. The present study was designed to examine the general hypothesis that cocaine induces apoptosis of coronary artery endothelium by suppressing nitric oxide synthesis, stimulating cytochrome c release from mitochondria and subsequently activation of the caspases cascade, which lead to endothelial cell apoptosis. …

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …

The Structure And Biological Features Of Fibrinogen And Fibrin, Michael W. Mosesson, Kevin R. Siebenlist, David A. Meh

Biomedical Sciences Faculty Research and Publications

Fibrinogen and fibrin play important, overlapping roles in blood clotting, fibrinolysis, cellular and matrix interactions, inflammation, wound healing, and neoplasia. These events are regulated to a large extent by fibrin formation itself and by complementary interactions between specific binding sites on fibrin(ogen) and extrinsic molecules including proenzymes, clotting factors, enzyme inhibitors, and cell receptors. Fibrinogen is comprised of two sets of three polypeptide chains termed Aα, Bβ, and γ, that are joined by disulfide bridging within the N-terminal E domain. The molecules are elongated 45-nm structures consisting of two outer D domains, each connected to a central E domain by …

Advances In Dna Affinity Chromatography, William Himanshu S. Gadgil

Theses and Dissertations (ETD)

Different aspects of DNA affinity chromatography such as DNA complexity heparin elution, the Bi-column method and the oligonucluotide trapping method were studied. The complexity (length) of a DNA sequence attached to an affinity chromatography column affects column retention, and the purity of transcription factors obtained. T18: A18 tailed DNA affinity columns were better suited for purification of most of the transcription factors than either the discrete or concatemeric DNA affinity columns. A novel method using heparin for eluting transcription factors from DNA Sepharose columns was characterized. The amount of the lac repressor chimera which eluted from the column was shown …

Acidification-Induced Sensitization To Thermoradiotherapy In Breast Cancer, Dennis B. Leeper, L T. Komarnicky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hyperthermia is an extensively studied cytotoxic agent, with strong radio- and chemosensitizing potential. Recent positive clinical trials combining superficial or deep heating techniques with radiation therapy strongly support a role for hyperthermia as an adjuvant to radiation. Many in vitro and in vivo studies have shown that acute extracellular acidification will compromise fundamental protective cellular responses and enhance tumor response to hyperthermia and chemotherapy.

Breast cancers, like most other tumors, exhibit elevated levels of lactate production that provides a basis for selective acidification. A phase I/II clinical trial is underway to test the hypothesis that hyperglycemia-induced acute acidification will sensitize …

Studies On The Formation Of Dna-Cationic Lipid Composite Films And Dna Hybridization In The Composites, Murali Sastry, Vidya Ramakrishnan, Mrunalini Pattarkine, Krishna N. Ganesh

Faculty Works

The formation of composite films of double-stranded DNA and cationic lipid molecules (octadecylamine, ODA) and the hybridization of complementary single-stranded DNA molecules in such composite films are demonstrated. The immobilization of DNA is accomplished by simple immersion of a thermally evaporated ODA film in the DNA solution at close to physiological pH. The entrapment of the DNA molecules in the cationic lipid film is dominated by attractive electrostatic interaction between the negatively charged phosphate backbone of the DNA molecules and the protonated amine molecules in the thermally evaporated film and has been quantified using quartz crystal microgravimetry (QCM). Fluorescence studies …

Neuromotor And Cognitive Development In Children With Cerebral Palsy In Relation To Neural Plasticity, Vaniecea Pollard

McCabe Thesis Collection

Infants with neurological disabilities, such as cerebral palsy (CP) and Down syndrome (DS), show severe delays in motor and cognitive development relative to chronological age. Involvement of neural plasticity as a treatment of such neurological disorders is increasingly being seen. Previous studies have found that interventions involving sensory linked motor performance have been critical in facilitating motor improvement. The purpose of this study was to compare self-initiated mobility in children with CP and DS. Three infants, ages 8, 9, and 22 months, with diagnoses of no CP, DS, and CP respectively, participated in the study. The infants were videotaped in …

Evidence For Two Mechanisms Of Amino Acid Osmolyte Release From Hippocampal Slices, R. Franco, M. E. Torres-Marquez, H. Pasantes-Morales

School of Veterinary and Biomedical Sciences: Faculty Publications

A 30% decrease in osmolarity stimulated ³H-taurine, ³H-GABA and glutamate (followed as ³H-D-aspartate) efflux from rat hippocampal slices. ³H-taurine efflux was activated rapidly but inactivated slowly. It was decreased markedly by 100 μM 5-nitro-(3-phenylpropylamino) benzoic acid (NPPB) and 600 μM niflumic acid and inhibited strongly by tyrphostins AG18, AG879 and AG112 (25–100 μM), suggesting a tyrosine kinase-mediated mechanism. Hyposmolarity activated the mitogen-activated protein kinases (MAPK) extracellular-signal-related kinase-1/2 (ERK1/ERK2) and p38, but blockade of this reaction did not affect ³H-taurine efflux. Hyposmosis also activated phosphatidyl-inositide 3-kinase (PI3K) and its prevention by wortmannin (100 nM) essentially abolished …

Sars, A Sara Homolog Repressible By Agr, Is An Activator Of Protein A Synthesis In Staphylococcus Aureus, Ambrose L. Cheung, Katherine Schmidt, Brian Bateman, Adhar C. Manna

Dartmouth Scholarship

The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A …

Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros

Dartmouth Scholarship

To understand the role of white collar-2 in theNeurospora circadian clock, we examined alleles ofwc-2 thought to encode partially functional proteins. We found that wc-2 allele ER24 contained a conservative mutation in the zinc finger. This mutation results in reduced levels of circadian rhythm-critical clock gene products, frq mRNA and FRQ protein, and in a lengthened period of the circadian clock. In addition, this mutation altered a second canonical property of the clock, temperature compensation: as temperature increased, period length decreased substantially. This temperature compensation defect correlated with a temperature-dependent increase in overall FRQ protein levels, with the …

Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green

Dartmouth Scholarship

Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or …

Increased Mrna Expression For The Α1 Subunit Of The GabaA Receptor Following Nitrous Oxide Exposure In Mice, Lisa M. Johanek, William E. Cullinan, Linda K. Vaughn

Biomedical Sciences Faculty Research and Publications

The mechanisms by which nitrous oxide (N₂O) produces physical dependence and withdrawal seizures are not well understood, but both N₂O and ethanol exert some of their effects via the GABA_A receptor and several lines of evidence indicate that withdrawal from N₂O and ethanol may be produced through similar mechanisms. Expression levels of mRNA transcripts encoding several GABA_A receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N₂O exposure would produce changes in mRNA expression for the α₁ subunit. Male, Swiss–Webster mice, 10–12 weeks of age, were …

Assessment Of Immune System Involvement In Tourette Syndrome, Ashley Dawn Levine

Loma Linda University Electronic Theses, Dissertations & Projects

Tourette syndrome (TS) is currently hypothesized to be the result of genetic and immunological components. This study investigated whether TS subjects produce IgG and IgA antibodies that bind to caudate nucleus, hippocampus, frontal cortex, cerebellum, thalamus, globus pallidus interior, exterior and putamen. Thirty- two children (14 TS, 7 family control, and 11 non-family control) and thirty-nine adults (11 TS, 14 family control, and 14 non-family control) were studied. Immunofluorescent studies were performed on basal ganglia tissue using serum from TS children and their family members. Brain antigens were prepared as two fractions (supernatant and pellet) and used as targets for …

Arsenic Alters The Function Of The Glucocorticoid Receptor As A Transcription Factor, Ronald C. Kaltreider, Alisa M. Davis, Jean P. Lariviere, Joshua W. Hamilton

Dartmouth Scholarship

Chronic human exposure to nonovertly toxic doses of arsenic is associated with an increased risk of cancer. Although its carcinogenic mechanism is still unknown, arsenic does not directly cause DNA damage or mutations and is therefore thought to act principally as a co-mutagen, co-carcinogen, and/or tumor promoter. Previous studies in our laboratory demonstrated that effects of low-dose arsenic (III) (arsenite) on expression of the hormone-regulated phosphoenolpyruvate carboxykinase (PEPCK) gene were strongly associated with the glucocorticoid receptor (GR)-mediated regulatory pathway. We therefore examined specifically the effects of arsenite on the biochemical function of GR in hormone-responsive H4IIE rat hepatoma cells. Completely …

Enhanced Expression Of Human Platelet-Derived Growth Factor In Pichia Pastoris, David M. Kaetzel

Pharmacology and Nutritional Sciences Faculty Patents

Enhanced yields of the platelet-derived growth factor (PDGF) B-chain are obtained using the Pichia pastoris yeast system. Yields of both wild-type and mutant human proteins are enhanced when the yeast is transformed with a vector containing the yeast mating factor promoter fused to a sequence encoding the mature protein. The secreted wild-type protein is indistinguishable from mature 29-32 kDa protein isolated from human and Chinese hamster ovary (CHO) cells. An RKK→EEE mutant exhibited reduced association with the cell surface and accumulated in the culture medium as 29-32 kDa forms. Stable transfection of U87 astrocytoma cells with RKK→EEE mutants of either …

Teratogen Update: Reproductive Risks Of Leflunomide (Arava); A Pyrimidine Synthesis Inhibitor: Counseling Women Taking Leflunomide Before Or During Pregnancy And Men Taking Leflunomide Who Are Contemplating Fathering A Child, Robert L. Brent

The Selected Works of Robert Brent

Arava™ (leflunomide) is a pyrimidine synthesis inhibitor used in the treatment of active rheumatoid arthritis (RA). The chemical name for leflunomide is N- (4’-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide. Because the drug has been successful in the treatment of rheumatoid arthritis (RA), it is being widely prescribed. In spite of the clear warning that the drug should not be prescribed for pregnant women, approximately 30 women have become pregnant while taking leflunomide as of December 1999. This commentary was prepared to aid teratology counselors and genetic counselors that might be contacted by physicians or patients about the risk of leflunomide exposure during pregnancy. Before the …

Truncated Forms Of The Dual Function Human Asct2 Neutral Amino Acid Transporter/Retroviral Receptor Are Translationally Initiated At Multiple Alternative Cug And Gug Codons, Chetankumar S. Tailor, Mariana Marin, Ali Nouri, Michael Kavanaugh, David Kabat

Biomedical and Pharmaceutical Sciences Faculty Publications

The sodium-dependent neutral amino acid transporter type 2 (ASCT2) was recently identified as a cell surface receptor for endogenously inherited retroviruses of cats, baboons, and humans as well as for horizontally transmitted type-D simian retroviruses. By functional cloning, we obtained 10 full-length 2.9-kilobase pair (kbp) cDNAs and two smaller identical 2.1-kbp cDNAs that conferred susceptibility to these viruses. Compared with the 2.9-kbp cDNA, the 2.1-kbp cDNA contains exonic deletions in its 3′ noncoding region and a 627-bp 5′ truncation that eliminates sequences encoding the amino-terminal portion of the full-length ASCT2 protein. Although expression of the truncated mRNA caused enhanced amino …

Health Professions Division Catalog Academic Year 2001-2002, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

The Process Of Clinical Trials: A Model For Successful Clinical Trial Participation, Cecile A. Lengacher, Lois L. Gonzalez, Rosemary Giuliano, Mary P. Bennett, Charles E. Cox, Douglas S. Reintgen

Nursing Faculty Publications

No abstract provided.