Medical Sciences Commons^™

Methods For Increasing Leptin Levels Using Nicotinic Acid Compounds, Elaine L. Jacobson, Myron Jacobson, Hyuntae Kim

Graduate Center for Nutritional Sciences Faculty Patents

The invention relates to the use of nicotinic acid and nicotinic acid esters, such as nicotinic acid alkyl esters, to increase the amount of leptin in a subject. As a result, one can treat conditions, such as conditions characterized by wounds, by administering sufficient amounts of nicotinic acid or nicotinic acid ester to increase leptin levels to alleviating amounts. Various conditions and modes of treatment are disclosed.

The Recombinant Adeno-Associated Virus Vector (Raav2)-Mediated Apolipoprotein B Mrna-Specific Hammerhead Ribozyme: A Self-Complementary Aav2 Vector Improves The Gene Expression, Shumei Zhong, Shihua Sun, Ba-Bie Teng

Faculty, Staff and Student Publications

BACKGROUND: In humans, overproduction of apolipoprotein B (apoB) is positively associated with premature coronary artery diseases. To reduce the levels of apoB mRNA, we have designed an apoB mRNA-specific hammerhead ribozyme targeted at nucleotide sequences GUA6679 (RB15) mediated by adenovirus, which efficiently cleaves and decreases apoB mRNA by 80% in mouse liver and attenuates the hyperlipidemic condition. In the current study, we used an adeno-associated virus vector, serotype 2 (AAV2) and a self-complementary AAV2 vector (scAAV2) to demonstrate the effect of long-term tissue-specific gene expression of RB15 on the regulation apoB mRNA in vivo. METHODS: We constructed a hammerhead ribozyme …

The Anti-Proliferation Effects Of Lycopene On Breast Cancer Cells, Tixieanna Dissmore

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The incidence and deaths from breast cancer represent the most cause of all cancer deaths among women. Lycopene, the carotenoid in tomatoes has been associated with decreasing risk of prostate, breast, and digestive tract cancers. Various mechanisms of lycopene action have been proposed, including antioxidant activity and pro-differentiation activities. Identifying changes in the expression of proteins modified by lycopene can provide information to study the modulating effects of lycopene carcinogenesis and tumorigenesis development.

Objective: The objective was to study the anti-proliferative effects of lycopene on MCF- 7 human breast cancer cells and to identify changes in protein expression patterns. …

Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Although many advances have been made in radiotherapy, tumor radioresistance and normal tissue damage continue to always be important issues for radiation oncologists. Numerous reports have also documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms. However, increasing evidence has suggested that anti-angiogenic therapy that targets tumor blood supply may alter abnormal tumor vasculature, thus synergizing radiotherapy. The governing hypothesis of the present study was that modification of tumor vasculature by antiangiogenic gene therapy can increase the efficacy of radiotherapy and that radiation can also improve DNA transfection efficiency by increasing expression of the administered gene. …

Endogenous No Regulates Superoxide Production At Low Oxygen Concentrations By Modifying The Redox State Of Cytochrome C Oxidase, Miriam Palacios-Callender, Marisol Quintero, Veronica S. Hollis, Roger J. Springett, Salvador Moncada

Dartmouth Scholarship

We have investigated in whole cells whether, at low oxygen concentrations ([O(2)]), endogenous nitric oxide (NO) modulates the redox state of the mitochondrial electron transport chain (ETC), and whether such an action has any signaling consequences. Using a polarographic-and-spectroscopic-coupled system, we monitored redox changes in the ETC cytochromes b(H), cc(1), and aa(3) during cellular respiration. The rate of O(2) consumption (VO(2)) remained constant until [O(2)] fell below 15 microM, whereas the onset of reduction of cytochromes aa(3), part of the terminal ETC enzyme cytochrome c oxidase, occurred at approximately 50 microM O(2). Incubation of the cells with an inhibitor of …

Alternative Therapies To Treat Cardiovascular Disease, Brent D. Jergens

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

The Cell Surface Receptor Slam Controls T Cell And Macrophage Functions, Ninghai Wang, Abhay Satoskar, William Faubion, Susumu Okamoto, Stefan Feske, Charles A. Gullo Phd, Kareem Clarke, Miriam Rodriguez Sosa, Arlene H. Sharpe, Cox Terhorst

Biochemistry and Microbiology

Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be a coregulator of antigen-driven T cell responses and is one of the two receptors for measles virus. Here we show that T cell receptor–induced interleukin (IL)-4 secretion by SLAM−/− CD4+ cells is down-regulated, whereas interferon γ production by CD4+ T cells is only slightly up-regulated. Although SLAM controls production of IL-12, tumor necrosis factor, and nitric oxide in response to lipopolysaccharide (LPS) by macrophages, SLAM does not regulate phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as a coreceptor …

Black And White: Structural And Functional Aspects Of Dermal Chromatophores Of The Marbled Whiptail Lizard (Cnemidophorus Marmoratus), James Swan

Masters Theses & Specialist Projects

The skin of reptiles is a complex organ with many sensory, regulatory and behavioral functions. Desert reptiles face a suite of challenges as their skin contacts hot-dry environmental surfaces. The marbled whiptail lizard, Cnemidophorus marmoratus (Lacertilia: Teiidae), is found in hot deserts of southeastern New Mexico and western Texas and is often above ground during the hottest times of the day. When active, these lizards encounter a broad range and intensity of visible and infrared wavelengths. The role of the integument in temperature regulation, although poorly understood, is critically important for these diurnal animals. Albedo, coloration, pattern, and in some …

Neuroscience: Its Relevance To Art Therapy And Art Therapy Education, Patrick Oates

EVMS School of Health Professions Theses & Dissertations

The development of contemporary neuroscience techniques has provided professionals in mental health fields with insight into the human brain and its functions. Literature searches revealed that there is very little research being conducted or existing literature that discusses the physiological response in the brain to the art therapy process. A more comprehensive understanding of the brain’s response to making art could enhance art therapists’ capacity to provide the most suitable treatment to meet the clients’ needs. This study was designed to explore the significance of neuroscience in art therapy, and art therapy education.

A questionnaire was emailed to 49 program …

Isolation And Characterization Of A Generalized Transducing Phage For Pseudomonas Aeruginosa Strains Pao1 And Pa14, Jonathan M. Budzik, William A. Rosche, Arne Rietsch, George A. O'Toole

Dartmouth Scholarship

A temperate, type IV pilus-dependent, double-stranded DNA bacteriophage named DMS3 was isolated from a clinical strain of Pseudomonas aeruginosa. A clear-plaque variant of this bacteriophage was isolated. DMS3 is capable of mediating generalized transduction within and between P. aeruginosa strains PA14 and PAO1, thus providing a useful tool for the genetic analysis of P. aeruginosa.

Conversion Of Myoblasts To Physiologically Active Neuronal Phenotype, Yumi Watanabe, Sei Kameoka, Vidya Gopalakrishnan, Kenneth D Aldape, Zhizhong Z Pan, Frederick F Lang, Sadhan Majumder

Faculty, Staff and Student Publications

Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress several terminal neuronal differentiation genes by binding to a specific DNA sequence (RE1/neuron-restrictive silencer element [NRSE]) present in their regulatory regions. REST-VP16 binds to the same RE1/NRSE, but activates these REST/NRSF target genes. However, it is unclear whether REST-VP16 expression is sufficient to cause formation of functional neurons either from neural stem cells or from heterologous stem cells. Here we show that the expression of REST-VP16 in myoblasts grown under muscle differentiation conditions blocked entry into the muscle differentiation pathway, countered endogenous REST/NRSF-dependent repression, activated the REST/NRSF target …

Method For Identifying Regulators Of Protein-Advanced Glycation End Product (Protein-Age) Formation, Elaine L. Jacobson, Myron Jacobson, Georg T. Wondrak

Graduate Center for Nutritional Sciences Faculty Patents

The invention relates to methods for identifying compounds which affect cellular stress. In particular, the method relates to identifying compounds which inhibit protein advanced glycation end product formation, where the compounds are carbonyl scavengers which inhibit the formation. The assay involves combing the substance of interest with histone H1 and ADP-ribose, and then measuring fluorescence and protein cross linking. Various inhibitors of protein AGE glycation have been identified, using this assay.

Marketable Features Of The Adapted Physical Education Career In Higher Education, Jiabei Zhang

Human Performance and Health Education Faculty Research

The purpose was to investigate marketable features of the adapted physical education (APE) career in higher education. A total of 560 APE job openings (297 APE first priority and 263 APE second priority were identified from the Chronicle of Higher Education between 1975-1976 and 1997-1998. These data were analyzed by regression, chi-square, and descriptive statistics. The results indicate that the APE career is a growing employment market demanding candidates who specialize in APE to prepare in one or more other areas and encouraging candidates who specialize in other areas to minor in APE. The market shows that APE second priority …

The Female Athlete Triad: Role Of The Coach In Prevention And Intervention, Michelle Turner Breiland

Theses and Graduate Projects

Introduction The Female Athlete Triad consists of disordered eating, amenorrhea, and osteoporosis. Eating disorders affect between 1-10% of adolescent and college age women (Haller, 1992),particularly in women's' sports in which leanness is considered important for performance such as cross-country running. Methods A three page 17 item questionnaire was sent out to 45 coaches of women's Division III cross-country teams in the Midwest region of the US. Descriptive statistics were run on the data. Results Results showed that 8% of coaches have coached an athlete with a diagnosed eating disorder. Of the top three topics for team discussions, 9% of coaches …

Combined Tlr And Cd40 Triggering Induces Potent Cd8+ T Cell Expansion With Variable Dependence On Type I Ifn, Cory L. Ahonen, Christie L. Doxsee, Sean M. M. Mcgurran, Tony R. Riter, William F. Wade, Richard J. Barth, John P. Vasilakos, Randolph J. Noelle, Ross M. Kedl

Dartmouth Scholarship

Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8⁺ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8⁺ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with …

The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley

Dartmouth Scholarship

AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types. We show that LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its …

Hearing Loss And Retarded Cochlear Development In Mice Lacking Type 2 Iodothyronine Deiodinase, Lily Ng, Richard J. Goodyear, Chad A. Woods, Mark J. Schneider

Dartmouth Scholarship

The later stages of cochlear differentiation and the developmental onset of hearing require thyroid hormone. Although thyroid hormone receptors (TRs) are a prerequisite for this process, it is likely that other factors modify TR activity during cochlear development. The mouse cochlea expresses type 2 deiodinase (D2), an enzyme that converts thyroxine, the main form of thyroid hormone in the circulation, into 3,5,3'-triiodothyronine (T3) the major ligand for TRs. Here, we show that D2-deficient mice have circulating thyroid hormone levels that would normally be adequate to allow hearing to develop but they exhibit an auditory phenotype similar to that caused by …

Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper

Dartmouth Scholarship

Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50 % lethal dose (LD₅₀) of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J) or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD₅₀ of CBA/J mice) died post infection, whereas CBA/J mice that received 15 …

Update - March 2004, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Christians Contemplating New Developments in Biomedicine
-- Editorial
-- Christian Principals of Genetic Intervention
-- Statement on Ethical Considerations Regarding Human Cloning
-- Honoring the Religious Impulse Within the Arena of Genetic Counseling

The Nad(P)H Oxidase Homolog Nox4 Modulates Insulin-Stimulated Generation Of H202 And Plays An Integral Role In Insulin Signal Transduction, Kalyankar Mahadev, Hiroyuki Motoshima, Xiangdong Wu, Jean Marie Ruddy, Rebecca S. Arnold, Guangjie Cheng, J. David Lambeth, Barry J. Goldstein

Department of Medicine Faculty Papers

Insulin stimulation of target cells elicits a burst of H₂O₂ that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative …

Indinavir And Rifabutin Drug Interactions In Healthy Volunteers., Walter K. Kraft, Jacqueline B. Mccrea, Gregory A. Winchell, Alexandra Carides, Richard C. Lowry, Eric J. Woolf, Sandra E. Kusma, Paul J. Deutsch, Howard E Greenberg, Scott A. Waldman

Department of Medicine Faculty Papers

Two studies examined the pharmacokinetics of indinavir and rifabutin when coadministered in healthy subjects. Rifabutin, which induces the expression of cytochrome P450 (CYP) 3A, and indinavir, which inhibits that enzyme system, are frequently coadministered in patients infected with HIV. The second study was undertaken to determine if altering the dose of rifabutin coadministered with indinavir would minimize the drug interaction observed in the first study. Two studies, each with a three-period crossover design, were performed. In study 1, standard doses of rifabutin and indinavir (300 mg of rifabutin qd and 800 mg indinavir q8h) were administered as monotherapy (with placebo …

Impacts Of Sara And Agr In Staphylococcus Aureus Strain Newman On Fibronectin-Binding Protein A Gene Expression And Fibronectin Adherence Capacity In Vitro And In Experimental Infective Endocarditis, Yan-Qiong Xiong, Arnold S. Bayer, Michael R. Yeaman, Willem Van Wamel, Adhar C. Manna, Ambrose L. Cheung

Dartmouth Scholarship

We investigated the impacts of sarA and agr on fnbA expression and fibronectin-binding capacity in Staphylococcus aureus in vitro and in experimental endocarditis. Although sarA up-regulated and agr down-regulated both fnbA expression and fibronectin binding in vitro and in vivo, fnbA expression was positively regulated in the absence of both global regulators. Thus, additional regulatory loci contribute to fnbA regulation and fibronectin-binding capacities in S. aureus.

Fibroblast Growth Factor 2 Endocytosis In Endothelial Cells Proceed Via Syndecan-4-Dependent Activation Of Rac1 And A Cdc42-Dependent Macropinocytic Pathway, Eugene Tkachenko, Esther Lutgens, Radu-Virgil Stan, Michael Simons

Dartmouth Scholarship

Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex …

Muc4 Mucin Expression In Human Pancreatic Tumours Is Affected By Organ Environment: The Possible Role Of Tgfbeta2., A. Choudhury, N. Moniaux, A. B. Ulrich, B. M. Schmied, J. Standop, Parviz M. Pour, S. J. Gendler, Michael A. Hollingsworth, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (P

Signaling Switches And Bistability Arising From Multisite Phosphorylation In Protein Kinase Cascades., Nick I Markevich, Jan B. Hoek, Boris N. Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior. Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation. Importantly, the reported kinetic properties of the kinase (MEK) and phosphatase (MKP3) of extracellular signal-regulated kinase (ERK) fulfill the essential requirements for generating a bistable switch at a single MAPK cascade level. Likewise, …

Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu

Nebraska Center for Virology: Faculty Publications

Rigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.

Feline immunodeficiency virus (FIV) was initially isolated in 1987 from a cat in California with severe immunodeficiency and has been recognized as a common worldwide feline pathogen (11, 14, 19, 20, 33). FIV-infected cats exhibit a …

Prognostic Indicators In Patients With Intracranial Tuberculoma: A Review Of 102 Cases, Mohammad Wasay, M. K. Moolani, J. Zaheer, Bhojo A. Khealani, R. A. Smego, A. R. Sarwari

Department of Medicine

Objective:

To see the characteristics, course and outcome of patients suffering from intracranial tuberculoma.

Methods:

Retrospective review of 102 patients diagnosed as intracranial tuberculoma at a tertiary care center over 10 years.

Results:

A total of 102 cases were seen with an age range of 1 to 75 years (mean, 30 years). Predisposing factors included Diabetes mellitus (8 patients) and pregnancy or puerperium (7 patients). Five pediatric patients had tuberculoma despite documented BCG vaccination. Fever (59%), headache (57%), meningeal irritation (36%) were the commonest presenting features; one-third of patients were drowsy or comatosed at presentation. Cerebrospinal fluid analysis was performed …

Somatotopic Representation Of Action Words In Human Motor And Premotor Cortex, Olaf Hauk, Ingrid Johnsrude, Friedemann Pulvermüller

Brain and Mind Institute Researchers' Publications

Since the early days of research into language and the brain, word meaning was assumed to be processed in specific brain regions, which most modern neuroscientists localize to the left temporal lobe. Here we use event-related fMRI to show that action words referring to face, arm, or leg actions (e.g., to lick, pick, or kick), when presented in a passive reading task, differentially activated areas along the motor strip that either were directly adjacent to or overlapped with areas activated by actual movement of the tongue, fingers, or feet. These results demonstrate that the referential meaning of action words has …

Trans-Snare Interactions Elicit Ca2+ Efflux From The Yeast Vacuole Lumen, Alexey J. Merz, William T. Wickner

Dartmouth Scholarship

Ca2+ transients trigger many SNARE-dependent membrane fusion events. The homotypic fusion of yeast vacuoles occurs after a release of lumenal Ca2+. Here, we show that trans-SNARE interactions promote the release of Ca2+ from the vacuole lumen. Ypt7p-GTP, the Sec1p/Munc18-protein Vps33p, and Rho GTPases, all of which function during docking, are required for Ca2+ release. Inhibitors of SNARE function prevent Ca2+ release. Recombinant Vam7p, a soluble Q-SNARE, stimulates Ca2+ release. Vacuoles lacking either of two complementary SNAREs, Vam3p or Nyv1p, fail to release Ca2+ upon tethering. Mixing these two vacuole populations together allows Vam3p and Nyv1p to interact in trans and …

Nucleic Acid Encoding Human Rev1 Protein, Zhigang Wang, Winston Lin, Hua Xin, Xiaohua Wu

Toxicology and Cancer Biology Faculty Patents

The present invention relates to a human cDNA homologous to the yeast REV1 gene. The sequence of human REV1 (hREV1) gene is described.