Medical Specialties Commons^™

Immune Cd8+ T Cells Prevent Reactivation Of Toxoplasma Gondii Infection In The Immunocompromised Host, Imtiaz A. Khan, William R. Green, Lloyd H. Kasper, Kathy A. Green, Joseph D. Schwartzman

Dartmouth Scholarship

Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immunosuppressed, patients with AIDS in particular. The cellular immune response, especially by gamma interferon (IFN-γ)-producing CD8⁺ T cells, is an essential component of protective immunity against the parasite. In the present study the role of CD8⁺ T cells during the reactivation of Toxoplasma infection in an immunocompromised murine model was evaluated. Chronically infected mice were challenged with LP-BM5 virus, and the kinetics of CD8⁺ T-cell function was studied. At 10 weeks after viral infection, mice showed obvious signs of systemic illness and began …

Subependymomas: Clinicopathologic Study Of 14 Tumors, Daniel F. Brown Md, Mba, Elizabeth J. Rushing Md

Department of Pathology & Laboratory Medicine

No abstract provided.

Differential Transcription Of The Tcpph Operon Confers Biotype-Specific Control Of The Vibrio Cholerae Toxr Virulence Regulon, Yvette M. Murley, Patricia A. Carroll, Karen Skorupski, Ronald K. Taylor, Stephen B. Calderwood

Dartmouth Scholarship

Epidemic strains of Vibrio cholerae O1 are divided into two biotypes, classical and El Tor. In both biotypes, regulation of virulence gene expression depends on a cascade in which ToxR activates expression of ToxT, and ToxT activates expression of cholera toxin and other virulence genes. In the classical biotype, maximal expression of this ToxR regulon in vitro occurs at 30 degrees C at pH 6.5 (ToxR-inducing conditions), whereas in the El Tor biotype, production of these virulence genes only occurs under very limited conditions and not in response to temperature and pH; this difference between biotypes is mediated at the …

Immune Responses Induced By Gene Gun Or Intramuscular Injection Of Dna Vaccines That Express Immunogenic Regions Of The Serine Repeat Antigen From Plasmodium Falciparum, Alexia A. Belperron, David Feltquate, Barbara A. Fox, Toshihiro Horii, David J. Bzik

Dartmouth Scholarship

The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110) of SERA. Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic …

Intermittent Antiretroviral Therapy (Art) Can Induce Reduction Of Viral Rebounding During Art-Interruption, Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

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 …

Clinical Trials In Alzheimer Disease: Debate On The Use Of Placebo Controls, Peter J. Whitehouse

Faculty Scholarship

During the past 10 years, there has been a rapidly growing number of pharmaceutical industry-sponsored drug trials for treatment of Alzheimer disease (AD) and other neurodegenerative diseases. As public awareness and concerns about AD have grown, so has interest in developing drug therapies for retarding symptom progression, delaying onset, and ultimately curing the disease. Ethical debate on the use of placebo control trials in AD research has come of age in the United States with the availability of treatments approved by the Food and Drug Administration. The experts and the public agree that more effective therapies are necessary, and new …

Interruption Of Multiple Cellular Processes In Ht-29 Epithelial Cells By Pseudomonas Aeruginosa Exoenzyme S, Joan C. Olson, Jennifer E. Fraylick, Eileen M. Mcguffie, Katherine M. Dolan, Timothy L. Yahr, Dara W. Frank, Timothy S. Vincent

Dartmouth Scholarship

Exoenzyme S (ExoS), an ADP-ribosylating enzyme produced by the opportunistic pathogen Pseudomonas aeruginosa, is directly translocated into eukaryotic cells by bacterial contact. Within the cell, ExoS ADP-ribosylates the cell signaling protein Ras and causes inhibition of DNA synthesis and alterations in cytoskeletal structure. To further understand the interrelationship of the different cellular effects of ExoS, functional analyses were performed on HT-29 epithelial cells after exposure to ExoS-producing P. aeruginosa 388 and the non-ExoS-producing strain 388DeltaS. Two different mechanisms of morphological alteration were identified: (i) a more-transient and less-severe cell rounding caused by the non-ExoS-producing strain 388DeltaS and (ii) a more-severe, …

Attachment Ligands Of Viable Toxoplasma Gondii Induce Soluble Immunosuppressive Factors In Human Monocytes, Jacqueline Y. Channon, Edward I. Suh, Rosanne M. Seguin, Lloyd H. Kasper

Dartmouth Scholarship

Previous studies have demonstrated that surface antigen proteins, in particular SAG-1, of Toxoplasma gondii are important to this parasite as attachment ligands for the host cell. An in vitro assay was developed to test whether these ligands and other secretory proteins are involved in the immune response of human cells to toxoplasma. Human monocytes were infected with tachyzoites in the presence of antiparasite antibodies, and their effect on mitogen-induced lymphoproliferation was examined. The presence of antibody to either parasite-excreted proteins (MIC-1 and MIC-2) or surface proteins (SAG-1 and SAG-2) during infection neutralized the marked decrease seen in mitogen-induced lymphoproliferation in …

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 …

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 …

Health Professions Division Catalog Academic Year 1999-2000, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Uwomj Volume 69, No 2, Spring 1999, Western University

University of Western Ontario Medical Journal

An interdisciplinary medical science publication; established 1930.

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

Spinal Cord Compression: Histologic Spectrum Of Lesions, I. N. Soomro, N.Kayani N.Kayani, Shahid Pervez, A. S. Hussainy, R. Ahmed, S. Muzaffar, S. A. Aziz, S. H. Hasan

Department of Pathology and Laboratory Medicine

Histologic diagnosis ultimately determines the prognosis and treatment of lesions causing spinal cord compression. Modem imaging techniques have revolutionized the procedure of localizing lesions pre¬senting with signs and symptoms of spinal cord compression. As a result, these lesions are more accessible for fine needle aspiration and biopsy. A quick diagnosis is possible if cytologic preparation is made. Similarly, intraoperative frozen section facility not only provides rapid diagnosis, but also offers oppor tunity of appropriate management decision there and then. Histology in many cases needs help of special stains and immunocytochemistry. This study looks at the histologic spectrum of these lesions, …

Soft Tissue Sarcomas: Pattern Diagnosis Or Entity, Naasha Talati, Shahid Pervez

Department of Pathology and Laboratory Medicine

Soft tissue sarcomas (STS) are a diverse and heterogeneous group of tumours The sub-classification of these tumours is of importance for both prognosis and treatment. Classically, sub- categorization is based purely on histomorphological grounds, but as new techniques evolve, a more, conclusive and accurate diagnosis can be made. This study describes the prevalence of soft tissue sarcomas in adults diagnosed at The Aga Khan University Hospital (AKUH) and the impact of immunohistochemistry(IHC) on the precise sub-categorization of these tumours. The study included 364 adults (age 16+) who were diagnosed as soft tissue sarcoma in the past six years (May 1991 …

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 …

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 …

Reaction-Diffusion Models Of Cancer Dispersion, Kim Yvette Ward

Mathematics & Statistics Theses & Dissertations

The phenomenological modeling of the spatial distribution and temporal evolution of one-dimensional models of cancer dispersion are studied. The models discussed pertain primarily to the transition of a tumor from an initial neoplasm to the dormant avascular state, i.e. just prior to the vascular state, whenever that may occur. Initiating the study is the mathematical analysis of a reaction-diffusion model describing the interaction between cancer cells, normal cells and growth inhibitor. The model leads to several predictions, some of which are supported by experimental data and clinical observations $\lbrack25\rbrack$. We will examine the effects of additional terms on these characteristics. …

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 …

Health Professions Division Catalog Academic Year 1998-1999, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

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 …

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 …

Stent Placement Compared With Balloon Angioplasty For Obstructed Coronary Bypass Grafts. Saphenous Vein De Novo Trial Investigators., M P Savage, J S Douglas, D L Fischman, C J Pepine, S B King, J A Werner, S R Bailey, P A Overlie, S H Fenton, J A Brinker, M B Leon, S Goldberg

Department of Medicine Faculty Papers

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts.

METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later.

RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate …

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 …

Transcranial Magnetic Stimulation Of The Prefrontal Cortex Delays Contralateral Endogenous Saccades, Tony Ro, Avishai Henik, Liana Machado, Robert D. Rafal

Publications and Research

The contributions of the superior prefrontal cortex (SPFC) and the superior parietal lobule (SPL) in generating voluntary endogenous and reflexive visually guided saccades were investigated using transcranial magnetic stimulation (TMS). Subjects made choice saccades to the left or right visual field in response to a central arrowhead (endogenous go signal) or a peripheral asterisk (exogenous go signal) that were presented along with a single TMS pulse at varying temporal intervals. TMS over the SPFC increased latencies for saccades made in response to an endogenous go signal toward the contralateral hemifield. No effects were observed when the go signal was exogenous …

Reference Serum Chemistry And Hematological Values For Spinal Cord Injured Patients, Michael S. Laymon, Antone L. Davis Ii

Loma Linda University Electronic Theses, Dissertations & Projects

Serum chemistry and hematological values from 220 traumatic spinal cord injured patients (157 male and 63 female between the ages of 15-47, with greater than six months from injury) were compiled via chart review. Traumatic spinal cord injured patient’s reference ranges were determined and compared with the general population reference ranges. Reference ranges within the spinal cord population were compared by age, gender, level of injury and chronicity of injury. The reference ranges determined for all groups within this spinal cord population fall within the reference ranges of the general population. This supports recent research which suggests that a decrease …

Molecular And Cellular Biology Of Prostate Cancer, El-Nasir Lalani, Marc Elie Laniado, Paul David Abel

Department of Pathology and Laboratory Medicine

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria …