Medicine and Health Sciences Commons^™

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Dartmouth Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican …

Oral Contraceptive Use And Risk Of Breast Cancer Among Women With A Family History Of Breast Cancer: A Prospective Cohort Study, Stephanie A. Navarro Silvera, Anthony B. Miller, Thomas E. Rohan

Department of Public Health Scholarship and Creative Works

Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large …

Cigarette Smoking And Risk Of Glioma: A Prospective Cohort Study, Stephanie A. Navarro Silvera, Anthony B. Miller, Thomas E. Rohan

Department of Public Health Scholarship and Creative Works

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. N‐nitroso compounds are known carcinogens, which are found in cigarette smoke and can induce gliomas in rats. On this basis, it has been hypothesized that cigarette smoking may be associated with an increased risk of glioma. We investigated the association between cigarette smoking and glioma risk in the National Breast Screening Study, which included 89,835 Canadian women aged 40–59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths …

Chromosomal Localization Of The Islet Neogenesis Associated Protein (Ingap) Gene In Syrian Hamster By Tyramide Signal Amplification-Fluorescence In Situ Hybridization (Tsa-Fish), Sallie A. Smith

Biological Sciences Theses & Dissertations

Diabetes mellitus is a group of conditions characterized by hyperglycemia due to an inability to produce or properly utilize insulin. The majority of cases fall into two categories, Type I and Type 2. Type I results from the autoimmune destruction of pancreatic β-cells of the islets. The beta cells are the exclusive source of insulin and the patient becomes entirely dependent on exogenous insulin to survive. Patients with Type 2 are distinguished by insulin resistance, a condition that develops due to the inability of the body to effectively use the insulin being produced. The β-cells gradually lose their ability to …

Expression Of G-Protein Inwardly Rectifying Potassium Channels (Girks) In Lung Cancer Cell Lines, Howard Plummer 3rd, Madhu Dhar, Maria Cekanova Ms, Rndr, Phd, Hildegard Schuller

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

BACKGROUND: Previous data from our laboratory has indicated that there is a functional link between the beta-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. METHODS: GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU) assay. RESULTS: GIRK1 mRNA was expressed in three of six small …

Expression Of G-Protein Inwardly Rectifying Potassium Channels (Girks) In Lung Cancer Cell Lines, Howard Plummer 3rd, Madhu Dhar, Maria Cekanova Ms, Rndr, Phd, Hildegard Schuller

Maria Cekanova MS, RNDr, PhD

BACKGROUND: Previous data from our laboratory has indicated that there is a functional link between the beta-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. METHODS: GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU) assay. RESULTS: GIRK1 mRNA was expressed in three of six small …

Neonatal Brain: Regional Variability Of In Vivo Mr Imaging Relaxation Rates At 3.0 T-Initial Experience, L. A. Williams, N. Gelman, P. A. Picot, D. S. Lee, J. R. Ewing, V. K. Han, R. T. Thompson

Anatomy and Cell Biology Publications

PURPOSE: To retrospectively investigate regional in vivo magnetic resonance,(MR). imaging transverse and longitudinal relaxation rates at 3.0 T in neonatal brain, the p relationship between these rates, and their potential use for gray matter (G),versus-M white matter (WM) tissue discrimination. MATERIALS AND METHODS: I Informed parental consent for performance of imaging procedures was obtained in each infant. Informed consent for retrospective image analysis was not required; ethics approval was obtained from institutional review board. At 3.0 T, R1 and R2 were measured in brain regions (frontal WM, posterior WM, periventricular WM, frontal GM, posterior GM, basal ganglia, and thalamus) in …

Glycemic Index, Glycemic Load, And Pancreatic Cancer Risk (Canada), Stephanie A. Navarro Silvera, Thomas E. Rohan, Meera Jain, Paul D. Terry, Geoffrey R. Howe, Anthony B. Miller

Department of Public Health Scholarship and Creative Works

There is some evidence that plasma insulin and post-load plasma glucose may be associated with the risk of pancreatic cancer. Glycemic index and glycemic load are measures, which allow the carbohydrate content of individual foods to be classified according to their postprandial glycemic effects and hence their effects on circulating insulin levels. Therefore, we examined pancreatic cancer risk in association with a glycemic index (GI), glycemic load (GL), and intake of dietary carbohydrate and sugar in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food frequency questionnaire between 1980 …

Glycemic Index, Glycemic Load, And Pancreatic Cancer Risk (Canada), Stephanie A. Navarro Silvera, Thomas E. Rohan, Meera Jain, Paul D. Terry, Geoffrey R. Howe, Anthony B. Miller

Department of Public Health Scholarship and Creative Works

There is some evidence that plasma insulin and post-load plasma glucose may be associated with the risk of pancreatic cancer. Glycemic index and glycemic load are measures, which allow the carbohydrate content of individual foods to be classified according to their postprandial glycemic effects and hence their effects on circulating insulin levels. Therefore, we examined pancreatic cancer risk in association with a glycemic index (GI), glycemic load (GL), and intake of dietary carbohydrate and sugar in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food frequency questionnaire between 1980 …

The Antitumor Agent, Arglabin-Dma, Preferentially Induces Apoptosis In Human Colon Tumor Cells, Sung Wook Kwon

Theses and Dissertations in Biomedical Sciences

Arglabin-DMA, an analog of farnesyl pyrophosphate (FPP), reportedly inhibits farnesyltransferase (FTase) directly by competitively blocking the binding of Ras protein and its posttranslational modification, as suggested in previous studies. But, the mechanisms by which Arglabin-DMA inhibits tumor growth in vivo and in vitro are still relatively poorly characterized. To determine the mechanism by which this drug inhibits tumor growth, the effects of Arglabin-DMA in two human colon tumor cell lines (mutant K-ras HCT 116 and wild-type ras HT-29) were explored on cell proliferation, apoptosis, and cell cycle kinetics in vitro. In cell viability studies, we showed that Arglabin-DMA …

5-Ht1b Receptor-Mediated Presynaptic Inhibition Of Gaba Release In The Suprachiasmatic Nucleus, Jayne R. Bramley, Patricia J. Sollars, Gary E. Pickard, F. Edward Dudek

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT_1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT_1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT_1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT_1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat …

Cutting Edge: Cd4+Cd25+ Regulatory T Cells Contribute To Gender Differences In Susceptibility To Experimental Autoimmune Encephalomyelitis, Jay Reddy, Hanspeter Waldner, Xingmin Zhang, Zsolt Illes, Kai W. Wucherpfennig, Raymond A. Sobel, Vijay K. Kuchroo

Jay Reddy Publications

Female B10.S mice are highly resistant to proteolipid protein (PLP) 139–151-induced experimental autoimmune encephalomyelitis (EAE) and depletion of PLP 139–151- reactive CD4+CD25+regulatory T (Treg) cells can slightly increase their EAE susceptibility. Although male B10.S mice are moderately susceptible to EAE, we report that depletion of Treg cells in male B10.S mice before immunization with PLP 139–151 renders them highly susceptible to severe EAE with more CNS neutrophil infiltrates than nondepleted controls. Increased susceptibility is associated with an enhanced PLP 139–151-specific T cell response and greater production of IFN-γ, IL-6, and IL-17. Male CD4+CD25+ effector cells depleted of Treg cells proliferate …

Role Of The Hypervariable Hinge Region Of Phosphoprotein P Of Vesicular Stomatitis Virus In Viral Rna Synthesis And Assembly Of Infectious Virus Particles, Subash C. Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The phosphoprotein (P protein) of vesicular stomatitis virus (VSV) is an essential subunit of the viral RNAdependent RNA polymerase and has multiple functions residing in its different domains. In the present study, we examined the role of the hypervariable hinge region of P protein in viral RNA synthesis and recovery of infectious VSV by using transposon-mediated insertion mutagenesis and deletion mutagenesis. We observed that insertions of 19-amino-acid linker sequences at various positions within this region affected replication and transcription functions of the P protein to various degrees. Interestingly, one insertion mutant was completely defective in both transcription and replication. Using …

Combining Cytotoxic And Immune-Mediated Gene Therapy To Treat Brain Tumors, James Curtin, Gwendalyn King, Marianela Candolfi, Remy Greeno, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all …

Nanosecond Pulsed Electric Fields: A New Stimulus To Activate Intracellular Signaling, Stephen J. Beebe, Karl H. Schoenbach

Bioelectrics Publications

When new technologies are introduced into the scientific community, controversy is expected and both excitement and disappointment enrich the lives of those who initiate the new ideas. It becomes the mission of the “inventors” to embrace the burden of proof to establish their ideas and convince the skeptics and disbelievers who will undoubtedly temper their enthusiasm and test their patience. While open mindedness is generally a scientific motto, those who review patents, manuscripts, and grants do not always readily practice it, even when the evidence is convincingly presented; old ideas and concepts often die hard. So it has been and …

Simulations Of Nanopore Formation And Phosphatidylserine Externalization In Lipid Membranes Subjected To A High-Intensity, Ultrashort Electric Pulse, Q. Hu, R. P. Joshi, K. H. Schoenbach

Bioelectrics Publications

A combined MD simulator and time dependent Laplace solver are used to analyze the electrically driven phosphatidylserine externalization process in cells. Time dependent details of nanopore formation at cell membranes in response to a high-intensity (100kV∕cm), ultrashort (10ns) electric pulse are also probed. Our results show that nanosized pores could typically be formed within about 5ns. These predictions are in very good agreement with recent experimental data. It is also demonstrated that defect formation and PS externalization in membranes should begin on the anode side. Finally, the simulations confirm that PS externalization is a nanopore facilitated event, rather than the …

Gene Therapy And Targeted Toxins For Glioma, James Curtin, Gwendalyn King, Marianela Candolfi, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted …

Replication And Encapsidation Of Papillomaviruses In Saccharomyces Cerevisiae, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Improvements in methodologies to recapitulate and study particular biological functions of the

papillomavirus life cycle have led to great advances in our knowledge of these viruses. Described in

this chapter are techniques that allow low-copy and high-copy replication of full-length human

papillomavirus (HPV) genomes, as well as assembly of virus-like particles, in Saccharomyces

cerevisiae (yeast). This system has several distinct advantages that make it an attractive complement

to the well-established raft-culturing system. First, yeast are inexpensive, rapid, and simple to culture

in the lab. Second, they provide an ever-widening array of genetic tools to analyze HPV functions

—most recently notable, …

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …

Biomarkers For Placental Abnormality, Cathal Mccarthy

Doctoral

Obstetrical complications including recurrent miscarriage, pre-eclampsia and intrauterine growth restriction (IUGR) affect 1%-5% of pregnant women (Younis and Samueloff 2003). Dysfunctional trophoblasts, impaired development of spiral arteries, imbalance in systems controlling the dilation and contraction of spiral arteries, placental fibrin clots and intervillous thrombosis are all possible factors that can result in an insufficient placental circulation. The combination of the hypercoagulable state of pregnancy and presence of genetic thrombophilic markets has the potential to induce placental thrombosis and cause placental insufficiency with subsequent obstetrical complications. The initial part of the research work involved examining the relationship between four common genetic …

Characterization Of Migrating Cells From Ventricular Zone (Vz) To Distant Limbic Structures After Multiple Neonatal Seizures, Melissa Corcia

Seton Hall University Dissertations and Theses (ETDs)

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