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Insulin-Like Growth Factor Ii Signaling In Neoplastic Proliferation Is Blocked By Transgenic Expression Of The Metalloproteinase Inhibitor Timp-1, David C. Martin, John L. Fowlkes, Bojana Babic, Rama Khokha

Pediatrics Faculty Publications

Insulin-like growth factor (IGF) II is overexpressed in many human cancers and is reactivated by, and crucial for viral oncogene (SV40 T antigen, [TAg])-induced tumorigenesis in several tumor models. Using a double transgenic murine hepatic tumor model, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP-1) blocks liver hyperplasia during tumor development, despite TAg-mediated reactivation of IGF-II. Because the activity of IGFs is controlled by IGF-binding proteins (IGFBPs), we investigated whether TIMP-1 overexpression altered the IGFBP status in the transgenic liver. Ligand blotting showed that IGFBP-3 protein levels were increased in TIMP-1-overexpressing double transgenic littermates, whereas IGFBP-3 mRNA levels were …

Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During

Department of Neurosurgery Faculty Papers

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant …

Signaling Mechanisms For Muscarinic Receptor-Mediated Coronary Vasoconstriction In Isolated Rat Hearts, Yi Zhang

Electronic Theses and Dissertations

The signaling mechanisms for muscarinic receptor-mediated vasoconstriction in coronary resistance arteries were studied in KCl-arrested isolated rat hearts perfused at a constant flow rate. The cholinergic agonists acetylcholine and bethanechol were given by bolus injection or constant infusion. The coronary vascular resistance was monitored by measuring the changes in perfusion pressure. The selective muscarinic agonist bethanechol caused a similar vasoconstrictor response as ACh, but with less potency and efficacy. Bolus injection of bethanechol evoked a phasic vasoconstriction in a dose-dependent manner, while infusion of bethanechol evoked a tonic vasoconstriction without producing tachyphylaxis. Coronary vascular responses to bethanechol were further examined …

Laser Skin Graft Harvesting Apparatus And Related Method, David S. Kirn

Surgery Faculty Patents

A laser dermatome is disclosed for harvesting and meshing grafts of skin. A roller driven by a motor lifts the leading edge of a portion of skin for cutting by a beam of light generated by a laser. Adhesive tape attached to the roller aids in lifting the portion of skin and is further utilized to secure the severed portion of skin to the roller. A stage mounted atop an axle supports the laser or a beam director. The movement of the stage is controlled by second and third motors which drive the stage along or rotate it about the …

Transfer Of Lacz Marker Gene To The Meniscus, Hideyuki Goto Md, Franklin D. Shuler Md, Phd, Chanin Lamsam Md, Hans D. Moller Md, Christopher Niyibizi Phd, Freddie H. Fu Md, Paul D. Robbins Phd, Christopher H. Evans Phd

Orthopaedics

Background: Lesions in the avascular two-thirds of the meniscus do not heal well and are of concern clinically. Various growth factors promote the synthesis of matrix by meniscal cells and thus have the potential to augment healing. However, their clinical application is severely hindered by problems with delivery. An attractive approach to overcoming such problems is to transfer genes that encode the growth factors in question to the site of the injury. As a prelude to this, we evaluated methods for delivering genes to the meniscus.

Methods: Gene transfer was evaluated in vitro and in vivo with a lacZ marker …

Digest Of The Philadelphia College Of Osteopathic Medicine (Summer 1999), Philadelphia College Of Osteopathic Medicine

Digest

The Summer 1999 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates
• Update on Clinical Education
• Board Profile
• Alumni Board Profile
• Convention Highlights
• Class Notes
• In Memoriam
• Coming Events

Identification And Characterization Of Determinants Of Head And Neck Tumor Cell Invasion, Yangguan Wu

Theses and Dissertations in Biomedical Sciences

Head and neck squamous cell carcinoma (HNSCC) is a common malignant disease with poor prognosis. The majority of patients die from local invasion or lymphatic metastasis. The mechanism(s) underlining the invasiveness of HNSCC are poorly understood. Utilizing a panel of HNSCC cell lines previously established in our laboratory, we tested the application and relevance of the three-step hypothesis of tumor invasion to HNSCC and investigated the mechanism(s) pertaining to the regulation of each step in the invasive process. Data presented in this thesis demonstrated that tumor cell invasion in HNSCC is a complex process involving three repeated sequential steps: adhesion, …

The Immunology Of Parturition, Ari Mayer Mackler

Loma Linda University Electronic Theses, Dissertations & Projects

Macrophage-derived factors have been implicated in the etiology of preterm labor but little is known about trafficking of this immune cell into the uterus or its regulation of uterine contractility in mice. Enhanced number and activation of macrophages was hypothesized to precede parturition. Studies characterized contractile activity and the distribution of macrophages in the uterus of C3/HeN mice before and after term (=day 19). Contractile activity by uterine strips on days 15 and 18 of pregnancy, the day of delivery, and 1 day postpartum indicate that an endogenous oscillator sustains high frequency contractions. Modest acceleration of the pacemaker occurred before …

Beta- And Gamma-Catenin Mutations, But Not E-Cadherin Inactivation, Underlie T-Cell Factor/Lymphoid Enhancer Factor Transcriptional Deregulation In Gastric And Pancreatic Cancer., K Caca, F T Kolligs, X Ji, M Hayes, J Qian, Alan M. Yahanda Md, Facs, D L Rimm, J Costa, E R Fearon

PCI Publications and Projects

Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to beta-catenin (beta-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3beta phosphorylation sites near the beta-cat NH2 terminus appear to render beta-cat resistant to regulation by APC and glycogen synthase kinase 3beta. In cells with APC or beta-cat defects, beta-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, beta-cat, …

The Accuracy Of Nitrous Oxide Passive Dosimeters As Compared With An Infra-Red Spectrographic Reference Method, Susan Allen

Community & Environmental Health Theses & Dissertations

Nitrous oxide is a gas often used in dental, surgical and veterinary operations as an anesthetic agent. Employees stationed in proximity of fugitive gas emissions may potentially suffer adverse health effects from chronic exposure to this agent. Passive dosimeters can be worn in the breathing zone of potentially affected personnel during exposure periods, then later analyzed to quantify nitrous oxide exposure. This study sought to establish the accuracy of several commercially available passive monitoring devices for nitrous oxide by comparison against an infra-red spectrophotometric reference method.

Role Of Gamma Interferon In Cellular Immune Response Against Murine Encephalitozoon Cuniculi Infection, Imtiaz A. Khan, Magali Moretto

Dartmouth Scholarship

Microsporidia are obligate intracellular protozoan parasites that cause a wide variety of opportunistic infection in patients with AIDS. Because it is able to grow in vitro, Encephalitozoon cuniculi is currently the best-studied microsporidian. T cells mediate protective immunity against this parasite. Splenocytes obtained from infected mice proliferate in vitro in response to irradiated parasites. A transient state of hyporesponsiveness to parasite antigen and mitogen was observed at day 17 postinfection. This downregulatory response could be partially reversed by addition of nitric oxide (NO) antagonist to the culture. Mice infected withE. cuniculi secrete significant levels of gamma interferon (IFN-γ). Treatment …

Insulinlike Growth Factor 1- And 2-Augmented Collagen Gel Repair Of Facial Osseous Defects, James S. Toung, Roy C. Ogle, Raymond F. Morgan, William H. Lindsey

School of Medical Diagnostics & Translational Sciences Publications

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models.

OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model.

METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with …

Induction Of Integral Membrane Pam Expression In Att-20 Cells Alters The Storage And Trafficking Of Pomc And Pc1, Giuseppe D. Ciccotosto, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Research

Peptidylglycine alpha-amidating monooxygenase (PAM) is an essential enzyme that catalyzes the COOH-terminal amidation of many neuroendocrine peptides. The bifunctional PAM protein contains an NH2-terminal monooxygenase (PHM) domain followed by a lyase (PAL) domain and a transmembrane domain. The cytosolic tail of PAM interacts with proteins that can affect cytoskeletal organization. A reverse tetracycline-regulated inducible expression system was used to construct an AtT-20 corticotrope cell line capable of inducible PAM-1 expression. Upon induction, cells displayed a time- and dose-dependent increase in enzyme activity, PAM mRNA, and protein. Induction of increased PAM-1 expression produced graded changes in PAM-1 metabolism. Increased expression of …

Fas-Fasl Interaction Involved In Pathogenesis Of Ocular Toxoplasmosis In Mice, Mark S. Hu, Joseph D. Schwartzman, Grant R. Yeaman, Jane Collins, Rosanne Seguin, Imtiaz A. Khan, Lloyd H. Kasper

Dartmouth Scholarship

Ocular toxoplasmosis is a potentially blinding intraocular inflammation. The intent of this study was to investigate the role of Fas-FasL interaction in a murine model of acquired ocular toxoplasmosis induced by intracameral inoculation of Toxoplasma gondii. Intraocular inflammation, Fas and FasL expression on lymphocytes and on ocular tissues, the occurrence of apoptosis, and the frequency of CD8⁺ and CD4⁺ T cells in the infected eyes were analyzed in C57BL/6 (B6) mice. Susceptibility to parasite-induced intraocular inflammation was observed in Fas-deficient (B6-lpr) and FasL-deficient (B6-gld) mice. Inoculation of 5,000 T. gondii tachyzoites induced significant …

Igf Paracrine And Autocrine Interactions Between Conceptus And Oviduct., A J Watson, M E Westhusin, Q A Winger

Obstetrics & Gynaecology Publications

Development in vitro is influenced by embryo density, serum, somatic cell co-culture and the production of 'embryotrophic' paracrine and autocrine factors. Research in our laboratory has focussed principally on the insulin-like growth factor (IGF) family. We have demonstrated that pre-attachment bovine and ovine embryos express mRNAs encoding a number of growth factor ligand and receptor genes including all members of the IGF ligand and receptor family throughout this developmental interval. In addition, early embryos express mRNAs encoding IGF-binding proteins (IGFBPs) 2-5 from the one-cell to the blastocyst stage and IGFBP5 mRNA at the blastocyst stage. Cultured bovine blastocysts release up …

Informing Research On Hiv Prevention: A Consultation, Sharon Fonn, C. Elizabeth Mcgrory

HIV and AIDS

According to a 1998 UNAIDS/WHO report, HIV infection among women is the fastest-growing segment of the AIDS pandemic, especially in developing countries. Unfortunately, the HIV-prevention strategies put forward by the public health community—monogamy, condom use, and treatment of sexually transmitted infections—are not feasible for many women. Women urgently need a means within their personal control to protect themselves against HIV. Recognizing this need, a number of international and nongovernmental organizations and government agencies have called for the development of microbicides, products that women could use vaginally to prevent infection with sexually transmitted infections, particularly HIV. The Population Council is one …

Department Of Radiology-Annual Executive Summary Report-July 1, 1998 To June 30, 1999, David C. Levin, M.D.

Department of Radiology Administrative Documents and Reports

102 page Department of Radiology Annual Executive Summary Report, July 1, 1998 to June 30, 1999, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

Vital Signs, Winter 1999, Boonshoft School Of Medicine

Vital Signs

A twenty four page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, alumni profiles, class notes, and more.

Study Of The Molecular Basis Of Diabetic Retinopathy, Heather Christine Glasscock-Hatcher

MUSC Theses and Dissertations

Abnormalities of the retinal vasculature contribute significantly to the development of diabetic retinopathy. In this study we have focused on two mechanisms which may be responsible-for the development and progression of this diabetic complication. Chronic hyperglycemia is associated with many of the vascular complications of diabetes mellitus; therefore, we examined mechanisms by which high-dose glucose damages retinal capillary endothelial cells. Our cell count results showed that high-dose glucose induces cell death in primary cultured human retinal capillary endothelial cells. Flow cytometry, in situ cell death detection, and transmission electron microscopy revealed that the cell death occurred via the apoptosis pathway …

Contributors

Coronary Artery Anomalies

No abstract provided.

Chapter 4: Normal And Anomalous Coronary Arteries In Humans. Part 1: Historical Background, Paolo Angelini, Salvado Villason, Albert V. Chan, Jr., Jose' G. Diez

Coronary Artery Anomalies

No abstract provided.

Trophectoderm Differentiation In The Bovine Embryo: Characterization Of A Polarized Epithelium., L C Barcroft, A Hay-Schmidt, A Caveney, E Gilfoyle, E W Overstrom, P Hyttel, A J Watson

Obstetrics & Gynaecology Publications

Blastocytst formation is dependent on the differentiation of a transporting epithelium, the trophectoderm, which is coordinated by the embryonic expression and cell adhesive properties of E-cadherin. The trophectoderm shares differentiative characteristics with all epithelial tissues, including E-cadherin-mediated cell adhesion, tight junction formation, and polarized distribution of intramembrane proteins, including the Na-K ATPase. The present study was conducted to characterize the mRNA expression and distribution of polypeptides encoding E-cadherin, beta-catenin, and the tight junction associated protein, zonula occludens protein 1, in pre-attachment bovine embryos, in vitro. Immunocytochemistry and gene specific reverse transcription--polymerase chain reaction methods were used. Transcripts for E-cadherin and …

Transient Expression Of A Translation Initiation Factor Is Conservatively Associated With Embryonic Gene Activation In Murine And Bovine Embryos., P A De Sousa, A J Watson, R M Schultz

Obstetrics & Gynaecology Publications

In the present study the abundance of mRNAs for eukaryotic translation initiation factors eIF-1A (formerly known as eIF-4C), -2alpha, -4A, -4E, and -5 was examined in in vivo-derived mouse embryos throughout preimplantation development using a semiquantitative reverse transcription-polymerase chain reaction assay. Although the mRNA profile for each gene is unique, only mRNA for eIF-1A transiently increases during embryonic gene activation (EGA) at the 2-cell stage, and this was confirmed by an independent hybridization-based assay. In in vitro-developed bovine embryos, mRNA for eIF-1A was transiently detected at the 8-cell stage, when the major activation of the genome occurs in this species. …

A Cross-Sectional Study Examining Lifestyle And Rheumatoid Arthritis, Leslie Nazaroff

Loma Linda University Electronic Theses, Dissertations & Projects

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the synovial joints. RA affects 0.5-2% of the population. Though it is predominantly a progressive disease, adjunct therapy may slow the destructive pathway or alleviate affiliated symptoms. This study examined the effects of lifestyle (diet and exercise) and self-efficacy on symptoms of RA as measured by disease activity and health satisfaction.

Methods. Seventy-five RA patients (77% female) from the Loma Linda University Faculty Medical Offices, Rheumatology Department completed self-assessment surveys on their lifestyle practices and RA affliction. Disease symptoms and activity were assessed with the Arthritis Impact Measurement …

Expression Of Toxoplasma Gondii-Specific Heat Shock Protein 70 During In Vivo Conversion Of Bradyzoites To Tachyzoites, Neide M. Silva, Ricardo T. Gazzinelli, Deise A. O. Silva, Eloisa A. V. Ferro, Lloyd H. Kasper, Jose R. Mineo

Dartmouth Scholarship

Stage conversion between bradyzoites and tachyzoites was investigated in C57BL/6 mice chronically infected with the ME-49 strain of Toxoplasma gondii. In order to promote bradyzoite-tachyzoite conversion, mice were treated in vivo with neutralizing doses of anti-gamma interferon (IFN-gamma) or anti-tumor necrosis factor alpha (TNF-alpha) antibodies. Expression of parasite-specific antigens SAG-1, SAG-2, and heat shock protein 70 (Hsp-70) was visualized in the central nervous system by immunocytochemistry and measured by photometric assay. The immunosuppressive effect of anti-IFN-gamma or anti-TNF-alpha treatment was immediate, leading to parasite stage conversion as indicated by the increased expression of tachyzoite-specific antigens (SAG-1 and SAG-2) and by …

Leukemia Inhibitory Factor (Lif): Murine Preimplantation Embryo Development, Implantation Rates, And Skeletal Development, Michael Hayes Mitchell

Theses and Dissertations in Biomedical Sciences

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which demonstrates perplexing physiological effects. It has been demonstrated that LIF is essential for implantation in mice. Little is known relating to the manner by which LIF effects pre-implantation and post-implantation development. The objectives of this project were to determine the effects LIF on pre-implantation development, to determine the effects that it may have on implantation rates, successful pregnancy rates, and resorption rates, and to determine the effects that LIF has on the skeletal development of mice. For the embryo transfer experiments, embryos were exposed to test compounds in the transfer medium …

Mouse Embryo Development In The Presence Of Capsaicin, Carlos Santiago Villar-Gosalvez

Theses and Dissertations in Biomedical Sciences

Capsaicin is the pungent agent found in hot peppers of the Capsicum genus. It is a potent neurotoxin that stimulates the degranulation and degeneration of C-afferent neurons. Capsaicin is widely used as a food condiment and medicine. Human exposure of capsaicin can exceed levels shown to be neurotoxic in laboratory animals. Additionally, capsaicin can cross the blood/placenta barrier and affect an embryo in utero. In order to assay the potential for toxicity to human embryos, mouse embryos were exposed to capsaicin and the effect of the capsaicin on embryo development was measured. Embryos were co-cultured in Krebs medium with 1% …

Department Of Radiology-Annual Report-July 1, 1997 To June 30, 1998, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Executive Summary Report, July 1, 1997 to June 30, 1998. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 103 pages.

Implantable Controlled Release Device To Deliver Drugs Directly To An Internal Portion Of The Body, Paul Ashton, Paul A. Pearson

Ophthalmology and Visual Science Faculty Patents

A simple and implantable sustained release drug delivery device with an inner core containing an effective amount of a low solubility agent covered by a non-bioerodible polymer coating layer that is permeable to the low solubility agent is disclosed. A method for treating a mammal to obtain a desired local or systemic physiological or pharmacological effect by surgically implanting such a sustained release drug delivery device into a mammal in need of treatment is also disclosed.

The Relation Of Weight Loss And Improved Fitness To Survival In Healthy Males, Joanna Lynn Bokovoy

Loma Linda University Electronic Theses, Dissertations & Projects

Obesity is a critical public health problem because of its prevalence, medical and psychosocial effects, and resistance to intervention. Weight loss in overweight individuals has been encouraged by the United States Public Health Service and by the medical community as a means for improving health. However, recent studies have suggested either positive or negative effects of weight loss on survival. It is possible that physical fitness may have a confounding effect, or be an effect modifier on survival in weight loss studies.

This study used Cox Regression analysis to address the separate and combined association of weight loss and improved …