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A Model Using Radiation And Pws4-Htnf-Α Gene Therapy For Treatment Of Glioblastomas, Angelo G. Baher

Loma Linda University Electronic Theses, Dissertations & Projects

The efficacy of radiotherapy for cancer is limited by the dose that can be safely delivered to the tumor without causing debilitating side effects. In addition, successful treatment of highly malignant tumors such as glioblastomas is likely to require adjunctive therapies to enhance tumor response to radiation. Previous studies have shown immunomodulation and a synergestic reduction in tumor volume of malignant tumors when tumor necrosis factor-α (TNF-α) protein is administered prior to radiation. The major goal of the present investigation was to evaluate the efficacy of pWS4-human TNF-α (pWS4-hTNF-α), a new plasmid construct that expresses human TNF-α protein, together with …

Regeneration In Periodontal Defects With Rhbmp-2 : A Dosage Study, Paola Guglielmoni

Loma Linda University Electronic Theses, Dissertations & Projects

Bone morphogenetic proteins (BMPs) have been shown to induce bone formation in ectopic and orthotopic sites. This inductive capability has led to their evaluation as possible adjuncts in periodontal reconstructive therapy. Indeed, studies have reported periodontal regeneration following surgical implantation of recombinant human BMP-2. This study evaluated regeneration of alveolar bone and cementum following periodontal reconstructive surgery including implantation of a construct consisting of sterile lyophilized rhBMP-2 in buffer adsorbed onto an absorbable collagen sponge. Critical size mandibular supra-alveolar periodontal defects were surgically created, and an incomplete block design was used to evaluate the regenerative potential of rhBMP-2 at 0.05, …

Na/K-Atpase-Mediated 86rb+ Uptake And Asymmetrical Trophectoderm Localization Of Alpha1 And Alpha3 Na/K-Atpase Isoforms During Bovine Preattachment Development., D H Betts, L C Barcroft, A J Watson

Obstetrics & Gynaecology Publications

This study evaluated Na/K-ATPase alpha 1- and alpha 3-subunit isoform polypeptide expression and localization during bovine preattachment development. Na/K-ATPase cation transport activity from the one-cell to blastocyst stage was also determined by measuring ouabain-sensitive 86Rb+ uptake. Both alpha1- and alpha 3-subunit polypeptides were detected by immunofluorescence to encircle the entire cell margins of each blastomere of inseminated zygotes, cleavage stage embryos, and morulae. Immunofluorescent localization of alpha1-subunit polypeptide in bovine blastocysts revealed an alpha1 immunofluorescence signal confined to the basolateral membrane margins of the trophectoderm and encircling the cell periphery of each inner cell mass (ICM) cell. In contrast, alpha …

Quantal Mechanisms Underlying Stimulation-Induced Augmentation And Potentiation, Hong Cheng

Electronic Theses and Dissertations

Repetitive stimulation of motor nerves causes an increase in the number of packets of transmitter ("quanta") that can be released in the ensuing period. This represents a type of conditioning, in which synaptic transmission may be enhanced by prior activity. Despite many studies of this phenomenon, there have been no investigations of the quantal mechanisms underlying these events, due to the rapid changes in transmitter output and the short time periods involved. To examine this problem, a method was developed in which estimates of the quantal release parameters could be obtained over very brief periods (3 s). Conventional microelectrode techniques …

The Baculovirus Anti-Apoptotic P35 Protein Promotes Transformation Of Mouse Embryo Fibroblasts., M Resnicoff, B. Valentinis, D. Herbert, D. Abraham, P D. Friesen, E. S. Alnemri, R Baserga

Department of Microbiology and Immunology Faculty Papers

The baculovirus p35 protein is a potent inhibitor of programmed cell death induced by a variety of stimuli in insects, nematodes, and mammalian cell lines. The broad ability of p35 in preventing apoptosis has led us to investigate its effect on mouse embryo fibroblasts in vitro and in vivo. For this purpose, we have used R- cells (3T3-like fibroblasts derived from mouse embryos with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes) and R508 cells (derived from R- and with 15 x 10(3) IGF-IRs per cell). Both cell lines grow normally in monolayer, but they do …

Oncolog, Volume 43, Number 04, April 1998, Sunita Patterson, Sunni Hosemann, Alison Ruffin, Mitchell Morris Md

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Molecular research leads to clinical trials for bladder cancer
• Patients to test exercise theory in quality-of-life study
• Practice guidelines and collaborative paths point the way
• Protocols: Bladder Cancer Clinical Trials Interventions Span Surgery, Chemotherapy, Radiotherapy, and Genetic Manipulation
• DiaLog: The New Math of Today’s Health Care, by Mitchell Morris, MD, Vice President for Information and Health Care Systems

Acute Blood Pressure Responses To Static And Dynamic Exercise: Racial Differences, Reuben Leon Wright

Theses and Dissertations in Urban Services - Urban Education

African Americans have a higher incidence of hypertension than other racial groups. Furthermore, some research suggests that normotensive individuals who exhibit exaggerated blood pressure (BP) responses to exercise may be at risk for future hypertension. This study sought to determine if normotensive African Americans exhibited exaggerated BP responses to static exercise or dynamic exercise relative to Caucasian Americans and Asian Americans. Thirty normotensive subjects participated from each of the three racial groups (15 males and 15 females). Subjects held 30% of maximal voluntary contraction (right knee extension) for 3 minutes, and BP was recorded during the third minute. On a …

The Role Of Glycoconjugates In Mediating Human Fertilization And Induction Of Fetomaternal Tolerance, Manish S. Patankar

Theses and Dissertations in Biomedical Sciences

Using the hemizona assay (HZA), a in vitro sperm-egg binding assay, we show that specific glycoconjugates known to inhibit immune cell interactions mediated by the selectins, potently block human sperm-egg binding. The selectin ligand sialyl Lewis^x inhibits sperm binding in the HZA by 60% at a concentration of 1 mg/ml. Our data indicates that glycodelin-A, a endometrial glycoprotein known to block sperm-egg binding in the HZA at low concentrations expresses unusual fucosylated lacdiNAc type glycans. The fucosylated lacdiNAc type sugars have been previously shown to be 15-20 fold more potent ligands of E-selectin. Glycodelin-S a seminal plasma glycoform of …

Mathematical Models Of Tumors And Their Remote Metastases, Carryn Bellomo

Mathematics & Statistics Theses & Dissertations

Clinical observations and indications in the literature have led us to investigate several models of tumors. For example, it has been shown that a tumor has the ability to send out anti-growth factors, or inhibitors, to keep its remote metastases from growing. Thus, we model the depleting effect of such a growth inhibitor after the removal of the primary tumor (thus removing the source) as a function of time t and distance from the original tumor r.

It has also been shown clinically that oxygen and glucose are nutrients critical to the survival and growth of tumors. Thus, we model …

Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan

Dartmouth Scholarship

Neospora caninum is a coccidial protozoan parasite that appears morphologically indistinguishable from Toxoplasma gondii and that infects a large range of mammals. Both inbred and outbred strains of mice exhibit a high degree of resistance to infection with N. caninum. Three inbred strains of mice (A/J, BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were protected against a lethal challenge from T. gondii. Vaccine-induced protection was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that had been vaccinated with N. caninum and challenged with T. gondii was observed. Adoptive transfer of CD8+ T-cell splenocytes …

Chlamydia Trachomatis Infection In The Female Reproductive Tract Of The Rat: Influence Of Progesterone On Infectivity And Immune Response, Charu Kaushic, Andrew D. Murdin, Brian J. Underdown, Charles R. Wira

Dartmouth Scholarship

As the most common cause of sexually transmitted disease in women, chlamydial infections can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To better understand the role played by sex hormones in modulating the immune response of the genital tract to microbial infections, we have developed a rat model to study Chlamydia trachomatis infection. Inbred female Lewis rats were primed with progesterone and inoculated by intrauterine instillation of C. trachomatis (mouse pneumonitis strain MoPn) into each uterine horn. When infected animals were examined for the presence of chlamydial antigens 14 days postinfection, both the uterus and vagina were found …

Investigation Of The Roles Of Toxin-Coregulated Pili And Mannose-Sensitive Hemagglutinin Pili In The Pathogenesis Of Vibrio Cholerae O139 Infection, Carol O. Tacket, Ronald K. Taylor, Genevieve Losonsky, Yu Lim

Dartmouth Scholarship

In this study, adult volunteers were fed tcpA and mshA deletion mutants of V. cholerae O139 strain CVD 112 to determine the role of toxin-coregulated pili (TCP) and mannose-sensitive hemagglutinin (MSHA) in intestinal colonization. Eight of 10 volunteers who received CVD 112 or CVD 112 ΔmshA shed the vaccine strains in their stools; the geometric mean peak excretion for both groups was 1.4 × 10⁵ CFU/g of stool. In contrast, only one of nine recipients of CVD 112 ΔtcpA shed vibrios in his stool (P < 0.01); during the first 24 h after inoculation, 3 × 10² CFU/g was recovered from this volunteer. All recipients of CVD …

Dna Methylation And Carcinogenesis In Digestive, Javed Yakoob, Fan Xue-Gong, Hu Guo-Ling, Zhang Zheng

Section of Gastroenterology

No abstract provided.

Immunopathogenesis Of A Spectrum Of Inflammatory Lung Diseases Induced By Experimental Reovirus Infection, Stephen Clifford Bellum

MUSC Theses and Dissertations

Inflammatory lung diseases cause a significant amount of morbidity and mortality. However, the mechanisms that control the initiation and resolution of pulmonary inflammatory responses have not been well-elucidated. Histopathological data suggests that the lung responds with a similar pattern of inflammation to diverse range of injurious stimuli. In order to investigate the immunopathogenesis of lung inflammation, a series of in vivo models of lung inflammation were generated in CBA/J and CD-I mice by respiratory reovirus 1/L infection. Using this approach, it was observed in CBA/J mice that a relatively low titer of reovirus 1/L induced a pattern of intraluminal fibrosis …

Digest Of The Philadelphia College Of Osteopathic Medicine (Winter 1998), Philadelphia College Of Osteopathic Medicine

Digest

The Winter 1998 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates
• Our Centennial
• Founders Day '98
• A Doctor's Helping Hand
• PCOM Honors Domenic A. Debias, Phd
• The Physician Assistant
• Mission Milestones
• Profiles
• Convention Highlights
• Class Notes
• Just Published
• In Memoriam
• Coming Events

Rapport Du Seminaire National [Au Mali] Pour La Definition D'Une Strategie D'Eradication De L'Excision, Population Council

Reproductive Health

This is a report on a workshop for the eradication of female genital mutilation (FGM) held in Bamako, Mali. The workshop presented the results of a literature review on FGM and the actions taken to counter the practice in Mali; provided updates on the activities of six national NGOs working on issues surrounding FGM; and developed a Plan of Action for activities aimed at reducing the practice. The workshop brought together 85 participants, including policy- and decisionmakers from the government, NGOs, and religious groups. The workshop led to the finalization of a national Plan of Action to the Year 2000 …

Effects Of Prenatal Drug Exposure On Neurobehavioral Functioning In Young Infants, Yvette Blanchard, Patricia E. Suess, Marjorie Beeghly

All PTHMS Faculty Publications

In the newborn period, infants prenatally exposed to cocaine and other drugs show low scores on the Neonatal Behavioral Assessment Scale. Beyond that period, research is limited on the effects of prenatal drug exposure on neurobehavioral functioning. In this study we compared infants exposed to cocaine and other drugs and control infants from low socioeconomic backgrounds on measures of neurobehavioral functioning during neuromotor assessment at 1, 4 and 7 months of life. None of the measures of neurobehavioral functioning showed any significant group differences. This study did not support the hypothesis of disrupted neurobehavioral functioning beyond the neonatal period in …

A Dichotomous Role For Nitric Oxide During Acute Toxoplasma Gondii Infection In Mice, Imtiaz A. Khan, Joseph D. Schwartzman, Tadashi Matsuura, Lloyd H. Kasper

Dartmouth Scholarship

Production of nitric oxide by macrophages is believed to be an important microbicidal mechanism for a variety of intracellular pathogens, including Toxoplasma gondii. Mice with a targeted disruption of the inducible nitric oxide synthase gene (iNOS) were infected orally with T. gondii tissue cysts. Time to death was prolonged compared with parental controls. Histologic analysis of tissue from infected mice showed scattered small foci of inflammation with parasites in various tissues of iNOS−/− mice, whereas tissue from the parental C57BL/6 mice had more extensive tissue inflammation with few visible parasites. In particular, extensive ulceration and necrosis of distal small …

Phosphorylation Of Elongation Factor 1 And Ribosomal Protein S6 By Multipotential S6 Kinase And Insulin Stimulation Of Translational Elongation, Y W Chang, J A Traugh

Faculty, Staff and Student Publications

Stimulation of protein synthesis in response to insulin is concomitant with increased phosphorylation of initiation factors 4B and 4G and ribosomal protein S6 (Morley, S. J., and Traugh, J. A. (1993) Biochimie 75, 985-989) and is due at least in part to multipotential S6 kinase. When elongation factor 1 (EF-1) from rabbit reticulocytes was examined as substrate for multipotential S6 kinase, up to 1 mol/mol of phosphate was incorporated into the alpha, beta, and delta subunits. Phosphorylation of EF-1 resulted in a 2-2. 6-fold stimulation of EF-1 activity, as measured by poly(U)-directed polyphenylalanine synthesis. The rate of elongation was also …

Permeable, Non-Irritating Prodrugs Of Nonsteroidal And Steroidal Agents, Paul Ashton, Thomas J. Smith, Peter G. Glavinos, John D. Conklin, Peter A. Crooks, Robert M. Riggs, Tadeusz Cynkowski, Grazyna Cynkowska

Ophthalmology and Visual Science Faculty Patents

Prodrugs containing an active drug molecule linked to a polyethylene glycol group, and a method of use thereof are described. Exemplary soluble ester prodrugs contain naproxen, triamcinolone acetonide, gancyclovir, taxol, cyclosporin, dideoxyinosine, trihydroxy steroids, and flurbiprofen molecules linked to polyethylene glycol (PEG) groups. Pharmaceutical compositions containing these prodrugs, and a method of using these esters for treating disease states or symptoms are also described.

Detection And Characterization Of Sp1 Binding Activity In Human Chondrocytes And Its Alterations During Chondrocyte Dedifferentiation., Rita M. Dharmavaram, Gang Liu, Sheryl D. Mowers, Sergio A. Jimenez

Department of Medicine Faculty Papers

We have detected DNA binding activity for a synthetic oligonucleotide containing an Sp1 consensus sequence in nuclear extracts from human chondrocytes. Changes in the levels of Sp1 oligonucleotide binding activity were examined in nuclear extracts from freshly isolated human chondrocytes, from chondrocytes that had been cultured under conditions that allowed the maintenance of a chondrocyte-specific phenotype on plastic dishes coated with the hydrogel poly(2-hydroxyethyl methacrylate), and from chondrocytes induced to dedifferentiate into fibroblast-like cells by passage in monolayer culture on plastic substrata. It was observed that Sp1 binding was 2-3-fold greater in nuclear extracts from dedifferentiated chondrocytes than in nuclear …

Foundation News: Fall 1997, University Of Health Sciences Foundation

Foundation News (1997)

Contents: UHS LiFE Challenge -- Foundation Faces -- Foundation Grants -- UHS Scholarships -- Gift Opportunities -- Foundation Activities -- UHS Foundation Board.

Metabolically Inactive Insulin Analog Prevents Type I Diabetes In Prediabetic Nod Mice, Dennis G. Karounos, J. Scott Bryson, D. A. Cohen

Internal Medicine Faculty Publications

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected …

The Type 2 Iodothyronine Deiodinase Is Expressed Primarily In Glial Cells In The Neonatal Rat Brain, Ana Guadaño-Ferraz, Maria Jesus Obregón, Donald L. St. Germain, Juan Bernal

Dartmouth Scholarship

Thyroid hormone plays an essential role in mammalian brain maturation and function, in large part by regulating the expression of specific neuronal genes. In this tissue, the type 2 deiodinase (D2) appears to be essential for providing adequate levels of the active thyroid hormone 3,5,3′-triiodothyronine (T3) during the developmental period. We have studied the regional and cellular localization of D2 mRNA in the brain of 15-day-old neonatal rats. D2 is expressed in the cerebral cortex, olfactory bulb, hippocampus, caudate, thalamus, hypothalamus, and cerebellum and was absent from the white matter. At the cellular level, D2 is expressed predominantly, if not …

Intrinsic And Extrinsic Control Of Hemopoietic Stem Cell Numbers: Mapping Of A Stem Cell Gene, Gerald De Haan, Gary Van Zant

Markey Cancer Center Faculty Publications

We evaluated in vivo interactions between extrinsic (growth factor induced) and intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle kinetics were assessed in eight strains of inbred mice using the cobblestone area–forming cell (CAFC) assay. A strong inverse correlation was observed between mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in the femur. The population size of primitive stem cells (CAFC day 35) varied widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling and quiescent), which were similar. Administration of …

Method For Employing The Delta Opioid Dadle To Extend Tissue Survival Time During Ischemia, Sufan Chien

Surgery Faculty Patents

This invention concerns a method for extending the survival time of mammalian lung tissue subjected to ischemia, by which said tissue is perfused with a preservation solution comprising a therapeutic dose of the delta opioid DADLE ([D-Ala²,D-Leu⁵]-Enkephalin) under hypothermic conditions.

Characterization Of The Fast Axonally Transported Proteins In The Rat Optic Pathway, Surafel Mulugeta

Theses and Dissertations in Biomedical Sciences

The fast axonally transported proteins represent a subset of neuronal proteins that are conveyed anterogradely as secretory vesicle constituents from the perikarya. Although fast transport displays properties consistent with the general secretory pathway, neuronal structure presents special problems which may require modifications of the general pathway. The elucidation of these special modifications is essential for a more complete understanding of neuronal function both in normal and pathological conditions. In order to characterize the fast transported (FT) proteins and to better understand fast transport trafficking, the FT of radiolabeled retinal ganglion cell (RGC) proteins in the adult rat optic pathway was …

The Cellular And Molecular Dynamics Of The Queuosine Modification In Transfer Rna: Definition, Modulation, Deficiencies And Effect Of The Queuosine Modification System, Rana C. Morris

Theses and Dissertations in Biomedical Sciences

The presence of the queuosine modification in the wobble position of tRNA^asn, tRN^asp, tRNA^his, and tRNA^tyr is associated with a decrease in cellular growth rate, an increase in the ability to withstand environmental stress, and differentiation of pleuripotent cells into mature phenotypes. The loss of this normal modification is strongly correlated with neoplastic transformation and tumor progression of a wide variety of cancers.

The "normal" system for formation of the queuosine modification in tRNA was studied in human fibroblast cell cultures and in mouse, rat and human liver tissues. The queuosine modification system …

Endothelial Nitric Oxide Synthase And Growth Factor Regulation Of Flow-Mediated Vascular Remodeling, David Anthony Tulis

Theses and Dissertations in Biomedical Sciences

This study was designed to characterize structural remodeling of male Wistar rat mesenteric arteries exposed to elevated blood flow in vivo for 1, 3, or 7 days. A series of arterial ligations induced blood flow increases in ileal and second-order branch arteries compared to same animal control vessels. Neither mean carotid nor local mesenteric arterial pressures changed significantly pre- to post-ligation. The primary flow-mediated force in both vessels was shear stress with possible involvement of acute stretch-induced wall stress in the ileal artery. Significant luminal expansion and medial wall hypertrophy occurred in the ileal and second-order arteries in a time-dependent …

Department Of Radiology-Annual Report-July 1, 1996 To June 30, 1997, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Report, July 1, 1996 to June 30, 1997. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 108 pages.