Medicine and Health Sciences Commons^™

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.

Topical Formulations For The Transdermal Delivery Of Niacin And Methods Of Treating Hyperlipidemia, Elaine L. Jacobson, Myron Jacobson, Hyuntae Kim, Moonsun Kim, Jaber G. Qasem

Graduate Center for Nutritional Sciences Faculty Patents

Niacin and niacin prodrugs are topically administered as suitable formulations to device for impoving the lipid profiles of subjects, preferably humans.

Scholarly Research Volume 1 Number 1, Touro College School Of Health Sciences

Yearbooks and Newsletters

First Issue presented by the Committee on Scholarly Research of the Touro College SHS. The Committee was formed in January 2003 and Chaired by M.A. Benjaminson, PhD.

Calcium And Glycolysis Mediate Multiple Bursting Modes In Pancreatic Islets, Richard Bertram, Leslie S. Satin, Min Zhang, Paul Smolen, Arthur Sherman

Pharmacology and Toxicology Publications

Abstract

Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10–60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca²⁺ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic β-cell that can account for these multimodal patterns. The model includes the feedback of …

The Genetic And Molecular Characterization Of The Polycystic Kidney Disease-Causing Mouse Gene Bicc1, Sarah J. Price

Theses, Dissertations and Capstones

Polycystic kidney disease (PKD) is one of the most common hereditary diseases and is characterized by progressive cyst formation, substantial renal enlargement, and frequently, progression to end-stage renal disease. One way to learn more about the etiology of this disease is to study mouse models that imitate the human situation. The juvenile congenital polycystic kidney disease (jcpk) gene on mouse Chromosome 10 has been found to cause a severe, early onset form of PKD when inherited in an autosomal recessive manner (Flaherty et al., 1995). Previous genetic studies mapped the jcpk locus to a 1 cM region on mouse Chromosome …

Roles Of Pkc Isozymes In Retinoic Acid-Induced B16 Mouse Melanoma Cell Growth Inhibition And Differentiation, Jianming Han

Theses, Dissertations and Capstones

Protein Kinase C (PKC) has been implicated in many cellular responses. Of the 11 isotypes in this family, seven are expressed in B16 mouse melanoma cells − PKCα, PKCδ, PKCε, PKCθ, PKCλ, PKCζ, and PKCµ.

Treatment of B16 cells with retinoic acid (RA) results in growth inhibition and differentiation. Simultaneously, RA induces a 6-8 fold increase of PKC α protein level, but only about 2-fold increase of PKC enzyme activity. The over- expression of wild type PKCα in B16 cells mimicked the action of RA. The over- expression of enzymatically inactive PKCα, either open or closed conformation, also inhibited B16 …

Docosahexaenoic Acid Modulates Class I Major Histocompatibility Complex Protein Function, Kaleb Marie Hypes

Theses, Dissertations and Capstones

Fatty acids influence immune responses, but how this occurs at the molecular level is not understood. Class I major histocompatibility complex molecules (MHC I), transmembrane proteins required for antigen presentation to T cell receptors, each consist of a 45kDa α chain noncovalently associated with a 12-kDa β₂-microglobulin (β₂m) molecule. Docosahexaenoic acid’s (DHA) effect on the binding of β₂m and anti-MHC I monoclonal antibodies (Mab) was measured. EL4 and RMA-S cells were cultured 48 hours with 0-45µM DHA or oleic acid. Murine to human β₂m exchange and Mab binding were assessed by fluorescence …

Fluorometric Measurements Of Conformational Changes In Glutamate Transporters, H. Peter Larsson, Anastassios V. Tzingounis, Hans-Peter Koch, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Glutamate transporters remove glutamate from the synaptic cleft to maintain efficient synaptic communication between neurons and to prevent extracellular glutamate concentrations from reaching neurotoxic levels (1). It is thought that glutamate transporters mediate glutamate transport through a reaction cycle with conformational changes between the two major access states that alternatively expose glutamate-binding sites to the extracellular or to the intracellular solution. However, there is no direct real-time evidence for the conformational changes predicted to occur during the transport cycle. In the present study, we used voltage-clamp fluorometry to measure conformational changes in the neuronal excitatory amino acid transporter …

Economic Efficiency And Consumer Choice Theory In Nutritional Labeling, Michael Mccann

Law Faculty Scholarship

As more Americans consume fast food each year, more Americans are contracting serious diseases related to obesity. Considering that obesity ranks second behind tobacco use as the largest contributor to mortality rates in the United States, and also that it gives rise to greater publicly funded health care expenses than does tobacco, this phenomenon begs the obvious question: To what extent does the growing consumption of fast food contribute to the obesity epidemic and the incidence of disease? If the answer indicates a meaningful contribution, a natural follow-up question then emerges: In a sensible legal system, what instruments would best …

Health Professions Division Catalog 2004-2005, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Intravenous 2-Deoxy-D-Glucose Injection Rapidly Elevates Levels Of The Phosphorylated Forms Of P44/42 Mitogen-Activated Protein Kinases (Extracellularly Regulated Kinases 1/2) In Rat Hypothalamic Parvicellular Paraventricular Neurons, Arshad Khan, Alan Watts

Selected Works Temporary Series

No abstract provided.

Cytoanalysis Of Pancreatic B-Cells: Using An Avian Model, Mammalian Tissue Culture And Implications Of Antisense Oligonucleotides Transfection, Ayman Salah-El-Deen Amer

Theses, Dissertations and Capstones

Calbindin-D_28k (CaBP_28K) is a vitamin D-dependent calcium-binding protein that may alter intracellular calcium ion levels, [Ca²⁺]i. This dissertation describes experiments done to gain an understanding of the potential role of CaBP_28k in pancreatic B-cells in control of insulin secretion. The localization of CaBP_28k and insulin in chicken pancreas are shown in Chapter 1. CaBP_28k expression was found to be highest in ventral and dorsal lobes and lowest in splenic lobe. Insulin concentrations were distributed similarly among these lobes. Confocal microscopic studies demonstrated colocalization of insulin and CaBP_28k in Bcells. These findings …

Trials, Tribulations, And Trends In Tumor Modeling In Mice, Joann C. L. Schuh

Toxicology and Animal Models in Research Collection

Selection of mouse models of cancer is often based simply on availability of a mouse strain and a known compatible tumor. Frequently this results in use of tumor models long on history but short on homology and quality control. Other factors including genetics, sex, immunological status, method and site of tumor implantation, technical competence, biological activity of the tumor, protocol sequence and timing, and selection of endpoints interact to produce outcomes in tumor models. Common reliance on survival and tumor burden data in a single mouse model often skews expectations towards high remission and cure rates; a finding seldom duplicated …

Trials, Tribulations, And Trends In Tumor Modeling In Mice, Joann C. L. Schuh

Biomedicine and Animal Models in Research Collection

Selection of mouse models of cancer is often based simply on availability of a mouse strain and a known compatible tumor. Frequently this results in use of tumor models long on history but short on homology and quality control. Other factors including genetics, sex, immunological status, method and site of tumor implantation, technical competence, biological activity of the tumor, protocol sequence and timing, and selection of endpoints interact to produce outcomes in tumor models. Common reliance on survival and tumor burden data in a single mouse model often skews expectations towards high remission and cure rates; a finding seldom duplicated …

Creation Of Non-Human Primate Neurogenetic Disease Models By Gene Targeting And Nuclear Transfer, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Genetically modified rhesus macaques are necessary because mouse models are not suitable for a number of important neurogenetic disorders; for example, Kallmann's syndrome, Lesch-Nyhan's disease and Ataxia-Telangiectasia. Mouse models may not be suitable because there may be no mouse ortholog of the human gene of interest, as is the case for Kallmann's syndrome, or because mutant mice do not exhibit the same phenotype observed in humans, as is the the case for Lesch-Nyhan's disease and Ataxia-Telangiectasia. Non-human primate models of neurogenetic diseases are expected to more closely resemble human diseases than existing mouse models. Genetically modified rhesus macaques can be …

Intravenous 2-Deoxy-D-Glucose Injection Rapidly Elevates Levels Of The Phosphorylated Forms Of P44/42 Mitogen-Activated Protein Kinases (Extracellularly Regulated Kinases 1/2) In Rat Hypothalamic Parvicellular Paraventricular Neurons, Khan, Alan Watts

Departmental Papers (Biology)

No abstract provided.

Renal Basolateral Transport Of Glucuronides And Other Organic Anions In Rat In Vitro Models, Sarah L. Miles

Theses, Dissertations and Capstones

Glucuronidation is a common Phase II biotransformation reaction that increases the hydrophilicity, and thus elimination, of toxins, xenobiotics, and endogenous compounds. Previous studies suggest that the kidney can secrete glucuronide conjugates, but the renal transport mechanisms for glucuronide secretion have not been determined. Based on the chemical nature of glucuronide metabolites, it is hypothesized that organic anion transporter (OAT) proteins along the basolateral membrane of the renal proximal tubule promote renal accumulation of glucuronide conjugates. The purpose of this study was to develop a rat renal proximal tubule model which demonstrates OAT activity and by which the contribution of OAT …