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Lamotrigine Treatment In Childhood Drug-Resistant Epilepsy, Nedret Uran, Gül Serdaroğlu, Şebnem Çalkavur, Erki̇n Serdaroğlu

Turkish Journal of Medical Sciences

Rationale: In this study the efficacy of Lamotrigine was evaluated in children with medically intractable epilepsy. Methods: 22 epileptic children, ranging between 4.2 years and 15 years of age (mean 9.3 years) were included in this study. Twelve (54.5%) were male and 10 (45.5%) were female. The seizure types were classified according to the International League Against Epilepsy criteria: simple partial seizures (8 cases), infantile spasms (4 cases), generalized tonic-clonic seizures (2 cases), tonic seizures (2 cases), complex partial seizure (2 cases), typical absence seizures (2 cases), myoclonic astatic seizures (1 case) and atypical absence seizures (1 case). The neurological …

High-Dose Intravenous Immunoglobulin Treatment In Intractable Childhood Epilepsy, Nedret Uran, Gül Serdaroğlu, Erki̇n Serdaroğlu, Sema Kalkan, Tuğrul Özcan

Turkish Journal of Medical Sciences

Rationale: Intractable childhood epilepsy is characterised by convulsions, which are resistant to treatment with adequate dosage, combination and duration of appropriate anticonvulsant drugs. Many clinical and experimental studies support the role of the immune mechanism in the pathogenesis of childhood epilepsy. The purpose of the present study is to ascertain the possible efficacy of intravenous immunoglobulin in the treatment of intractable childhood epilepsy. Methods: The children aged 4-8 years suffering from intractable childhood epilepsy were treated with high-dose intravenous immunoglobulin (400 mg/kg) 5 times in the first week, on the 15th and 30th days. The treatments were repeated every 4 …

Experimentally Developed Secondaryechinococcosis In Pleural And Peritoneal Cavitiesand The Utility Of Serological Tests During Thefollow Up, Kadi̇r Kazez, Mustafa Şahi̇n, Celaletti̇n Vatansev, Yücel Aritaş, Faruk Aksoy, Hüsametti̇n Vatansev

Turkish Journal of Medical Sciences

Secondary echinococcosis is an important complication of hydatid disease and is not rare in the peritoneal cavity. However, the frequency of secondary hydatidosis in the pleural cavity is not very well known. This study was planned to elicit the frequency of secondary cyst development in the pleural cavity, and to compare this with secondary peritoneal hydatidosis. It was also intended to follow up cyst development by serological tests. Twelve white female Island rabbits were used. The mean weight of the rabbits was 2450±420 g. Cystic fluid containing protoscolex, hydatid sand and germinative membrane homogenate was injected via an 18 F …

Effect Of Actinomycin D And Cycloheximide On Ischemic Preconditioning-Induced Delayed Cardioprotective Effect In Rats, Devinder Singh, Ajay Sharma, Manjeet Singh

Pharmacy Faculty Articles and Research

The present study was designed to investigate the effect of actinomycin D, a transcription inhibitor, and cycloheximide, a translation inhibitor, on the delayed cardioprotective effect of ischemic preconditioning. Left thoracotomy was performed in anaesthetized rats at 4th/5th intercostal space and polypropylene suture (5-0) was employed to occlude left common coronary artery. Ischemic preconditioning was produced by four episodes of 5 min of coronary artery occlusion followed by 5 min of reperfusion and thoracic cavity was sutured. Left thoracotomy was performed again after 24 hr of ischemic preconditioning and left coronary artery was occluded for 30 min followed by reperfusion for …

The Relationship Between Functional And Histological Changes In Muscle Following Eccentric Exercise In Mice, Michael John Newton

Theses: Doctorates and Masters

Exercise-induced muscle damage (EIMD) is known to be produced by novel or unaccustomed exercise, especially high force eccentric contractions. Histological myofibre disruption, force loss and muscle soreness are associated with EIMD and have implications for sporting performance. Traditional practices of assessing the extent of disruption to the myofibres is by performing needle biopsies and subsequently analysing the histology of the fibres. Recently there has been interest in investigating whether changes in force production and contractile properties of muscle following damaging exercise correlate strongly with the magnitude of disruption to the myofibres. The main aim of this study was to investigate …

Isovolumic Regulation In Nervous Tissue: A Novel Mechanism Of Cell Volume Regulation, O. Quesada, R. Franco, K. Hernandez-Fonseca, K. Tuz

School of Veterinary and Biomedical Sciences: Faculty Publications

Cell volume regulation is a property present in most animal cell lineages that allows them to recover their original volume after events of swelling or shrinkage. Such events can be caused by changes in external osmolarity or to osmotic gradients generated during normal cell functioning.4,6 The mechanism of cell volume regulation involves transmembrane fluxes of osmotically active solutes in the necessary direction to counteract the net gain or loss of intracellular water.9 The process through which cells recover their normal volume after swelling is named Regulatory Volume Decrease (RVD). This consists of the efflux of inorganic osmolytes, such as K …

A Cultivated Taste For Yeast., C Brenner

Kimmel Cancer Center Faculty Papers

The availability of complete genomic sequences of Saccharomyces cerevisiae has catalyzed a cultural change in the practice of yeast biology, providing opportunities to develop high throughput techniques to define protein function, to define drug targets, and to discover and characterize drugs.

The Global Carbon Metabolism Regulator Crc Is A Component Of A Signal Transduction Pathway Required For Biofilm Development By Pseudomonas Aeruginosa, George A. O'Toole, Karine A. Gibbs, Paul W. Hager, Paul V. Phibbs, Roberto Kolter

Dartmouth Scholarship

The transition from a planktonic (free-swimming) existence to growth attached to a surface in a biofilm occurs in response to environmental factors, including the availability of nutrients. We show that the catabolite repression control (Crc) protein, which plays a role in the regulation of carbon metabolism, is necessary for biofilm formation in Pseudomonas aeruginosa. Using phase-contrast microscopy, we found that a crc mutant only makes a dispersed monolayer of cells on a plastic surface but does not develop the dense monolayer punctuated by microcolonies typical of the wild-type strain. This is a phenotype identical to that observed in mutants …

Spin Trapping Pharmaceutical Compositions And Methods For Use Thereof, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Other preferred spin-trapping agents include 5,5-dimethyl pyrroline N-oxide, (DMPO), α-(4-pyridyl-1-oxide)-N-tert-butylnitrone, (POBN), and (TEMPO) spin-trapping derivatives thereof. …

Increased Severity Of Murine Infection With Toxioplasma Gondii Following Vitaman E And Selenium Supplementatoin, Susan Mccarthy

Masters Theses & Specialist Projects

At present, toxoplasmosis is one of the most common opportunistic infections in immunocompromised patients. The need for a reliable experimental model is crucial not only for achieving a better understanding of the pathophysiology of this infection but also for developing a better method to evaluate new therapeutic regimens. This study was organized to determine if the antioxidants vitamin E and selenium would provide a beneficial effect in mice chronically infected with Toxoplasma gondii. In the first phase of the study, 35 female Swiss Webster mice were infected with oocysts of the Me49 strain of Toxoplasma gondii while receiving diets supplemented …

Screening For Mutants In The Output Pathway Of The Circadian Clock In Chlamydomonas Reinhardtii, Wei Yuan

Masters Theses & Specialist Projects

The circadian clock is a basic component of biological systems and has been found in many organisms. It is composed by three major components: the input pathway, the oscillator and the output pathway. The purpose of this research is to study the output pathway of the circadian clock in Chlamydomonas reinhardtii strain Carnil by screening mutants, which were generated by insertional mutagenesis via glass bead transformation. The plasmid pSP124S containing the ble marker was used to introduce mutations. The CABII-1 gene has been reported to show a circadian rhythm in expression. The reporter gene ARS2 that was transcriptionally fused to …

Genetic Control Of Eye Development, A Case Study Focused On The Murine Mutation Belly Spot And Tail (Bst), Qing Tang

Theses and Dissertations (ETD)

Development of the eye is controlled by a network of genes, often conserved, that regulate the timing and location of cellular differentiation. One approach to understanding this network of genes and their interaction is to focus on mutations, spontaneous or induced, that predictably disrupt the proper function of such networks, and by examining the effect of such disruption on the function of other genes.

The Belly spot and tail (Bst) semi-dominant mutation, mapped to mouse Chromosome 16, leads to developmental defects of the eye, skeleton, and coat pigmentation. In the eye, the mutant phenotype is characterized by the presence of …

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 …

Cartilage Regeneration On A Large Articular Surface Facilitated By Stress Shielding, Charles L. Mcdowell, Jennifer S. Wayne, Robert Tuten, Hunter H. Mcguire Jr.

Virginia Journal of Science

An animal model for the study of articular cartilage regeneration in-vivo facilitated by stress-shielding is introduced. The object of the model is to test the hypothesis that some form of cartilaginous tissue will grow upon a large joint surface in vivo with the joint in normal motion. The model utilizes the known capability of immature cells to differentiate. The source of cells is bleeding subchondral bone. In addition, the model provides a mechanically shielded environment in which cell differentiation and maturation can occur. The study showed that a substantial amount of tissue will grow in the animal model only when …

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 …

Phosphoinositide-Ap-2 Interactions Required For Targeting To Plasma Membrane Clathrin-Coated Pits., I Gaidarov, James H. Keen

Department of Microbiology and Immunology Faculty Papers

The clathrin-associated AP-2 adaptor protein is a major polyphosphoinositide-binding protein in mammalian cells. A high affinity binding site has previously been localized to the NH(2)-terminal region of the AP-2 alpha subunit (Gaidarov et al. 1996. J. Biol. Chem. 271:20922-20929). Here we used deletion and site- directed mutagenesis to determine that alpha residues 21-80 comprise a discrete folding and inositide-binding domain. Further, positively charged residues located within this region are involved in binding, with a lysine triad at positions 55-57 particularly critical. Mutant peptides and protein in which these residues were changed to glutamine retained wild-type structural and functional characteristics by …

Method Of Protecting Against Neuron Loss, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Patents

The present invention pertains to a method of protecting against neuron loss in a subject by administering a compound that protects against neuron loss by acting through a vitamin D receptor. Some of these compounds may prevent or retard neuron loss by regulating intraneuronal and/or peripheral calcium and phosphate levels. Other compounds of the invention act through a vitamin D receptor to protect against neuron loss through mechanisms not involving calcium or phosphate regulation. A preferred compound is a biologically active form of vitamin D, a precursor, metabolite, or analog of vitamin D. A preferred form of vitamin D is …

The Localization Of Gaba-Like Immunoreactivity In The Optic Lobe Neuropils And Optic Tracts Of The Cockroach Leucophaea Maderae, David Guffey

Masters Theses & Specialist Projects

Gamma aminobutyric acid (GABA) is a prominent neurotransmitter found in both vertebrates and invertebrates. The action of GABA has been accepted to be inhibitory in nature, but recent evidence suggests it is both inhibitory and excitatory, depending upon time of day. The amount of GABA measured in the brain of the cockroach Leucophaea maderae was discovered to fluctuate in a circadian pattern similar to the pattern of electrical output measured from the optic nerve in L. maderae. Considering the circadian oscillator for L. maderae has been localized to the optic lobes of the brain, the discovery of GABA-like immunoreactivity in …

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 …

Dichotomy Between Naïve And Memory Cd4+ T Cell Responses To Fas Engagement, J. Desbarats, T. Wade, W. F. Wade, M. K. Newell

Dartmouth Scholarship

Engagement of Fas (APO-1, CD95), a member of the tumor necrosis factor receptor superfamily, can induce apoptotic cell death. However, Fas engagement also can costimulate lymphocyte proliferation. The physiologic regulation of these two outcomes is poorly understood. Here, we have used two systems, the first in vitro and the second in vivo, to demonstrate that naïve and memory CD4+ T cells display dichotomous responses to Fas ligation. Naïve CD4+ T cells (CD44lo, CD45RB+, CD62L+) die as a consequence of Fas ligation in the presence of anti-CD3 antibody, whereas memory T cells (CD44hi, CD45RB−, CD62L−), freshly isolated from the same …

Core-Binding Factor Influences The Disease Specificity Of Moloney Murine Leukemia Virus, Amy F. Lewis, Terryl Stacy, William R. Green, Lekidelu Taddesse-Heath, Janet W. Hartley, Nancy A. Speck

Dartmouth Scholarship

The core site in the Moloney murine leukemia virus (Moloney MLV) enhancer was previously shown to be an important determinant of the T-cell disease specificity of the virus. Mutation of the core site resulted in a significant shift in disease specificity of the Moloney virus from T-cell leukemia to erythroleukemia. We and others have since determined that a protein that binds the core site, one of the core-binding factors (CBF) is highly expressed in thymus and is essential for hematopoiesis. Here we test the hypothesis that CBF plays a critical role in mediating pathogenesis of Moloney MLV in vivo. We …

Interaction Between Fgf And Bmp Signaling Pathways Regulates Development Of Metanephric Mesenchyme., Andrew T. Dudley, R. E. Godin, E. J. Robertson

Journal Articles: Genetics, Cell Biology & Anatomy

Nephrogenesis in the mouse kidney begins at embryonic day 11 and ends approximately 10 days postpartum. During this period, new nephrons are continually being generated from a stem-cell population-the nephrogenic mesenchyme-in response to signals emanating from the tips of the branching ureter. Relatively little is known about the mechanism by which the nephrogenic mesenchyme cell population is maintained at the tips of the ureter in the presence of signals promoting tubulogenesis. Previous studies have shown that a loss of Bmp7 function leads to kidney defects that are a likely result of progressive loss of nephrogenic mesenchyme by apoptosis. The studies …

Study Of The Baig Gene In Bile Acid 7Α-Dehydroxylating Bacteria, Michael David

Masters Theses & Specialist Projects

Recently, intestinal bile acid 7α-dehydroxylating bacteria have been implicated in cholesterol gallstone disease. Eubacterium sp. strain V.P.I. 12708, a bile acid 7α-dehydroxylating bacteria, contains multiple bile acid inducible (bai) genes which are located on a large bai operon. Genes of this operon encode the enzymes responsible for bile acid 7α-dehydroxylation. The baiG gene encodes a bile acid transporter in Eubacterium sp. strain V.P.I. 12708. Utilizing the polymerase chain reaction I determined the presence or absence of baiG-like genes in six bile acid 7α-dehydroxylating strains: Clostridium sp. Strain TN-271, Eubacterium sp. strain 1-10, Clostridium bifermentans strain 1-55, Clostridium sordellii strain Y67, …

Local And Global Stereopsis In The Horse., B Timney, K Keil

Brain and Mind Institute Researchers' Publications

Although horses have laterally-placed eyes, there is substantial binocular overlap, allowing for the possibility that these animals have stereopsis. In the first experiment of the present study we measured local stereopsis by obtaining monocular and binocular depth thresholds for renal depth stimuli. On all measures, the horses' binocular performance was superior to their monocular. When depth thresholds were obtained, binocular thresholds were several times superior to those obtained monocularly, suggesting that the animals could use stereoscopic information when it was available. The binocular thresholds averaged about 15 min arc. In the second experiment we obtained evidence for the presence of …

Signal Transducer And Activator Of Transcription (Stat)5 Activation By Bcr/Abl Is Dependent On Intact Src Homology (Sh)3 And Sh2 Domains Of Bcr/Abl And Is Required For Leukemogenesis., M Nieborowska-Skorska, M A Wasik, A Slupianek, P Salomoni, T Kitamura, B Calabretta, T Skorski

Department of Microbiology and Immunology Faculty Papers

Signal transducer and activator of transcription (STAT)5 is constitutively activated in BCR/ ABL-expressing cells, but the mechanisms and functional consequences of such activation are unknown. We show here that BCR/ABL induces phosphorylation and activation of STAT5 by a mechanism that requires the BCR/ABL Src homology (SH)2 domain and the proline-rich binding site of the SH3 domain. Upon expression in 32Dcl3 growth factor-dependent myeloid precursor cells, STAT5 activation-deficient BCR/ABL SH3+SH2 domain mutants functioned as tyrosine kinase and activated Ras, but failed to protect from apoptosis induced by withdrawal of interleukin 3 and/or serum and did not induce leukemia in severe combined …

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 …

Technique For Specifying The Fatty Acid At The Sn2 Position Of Acylglycerol Lipids, Robert C. Dickson, Robert L. Lester, M. Marek Nagiec

Molecular and Cellular Biochemistry Faculty Patents

A method for specifying a fatty acid at the sn2 position of acylglycerol lipids including (a) transfecting a vector including the SLC1 gene or a variant thereof into embryonic biological material, and (b) allowing the SLC1 gene to specify the type of fatty acid at the sn2 position of acylglycerol lipids. Also provided for is an isolated SLC1 gene and a probe for its detection.

Nucleotide Sequences For Detection Of Serpulina Hyodysenteriae, Gerald E. Duhamel, Robert Elder

School of Veterinary and Biomedical Sciences: Faculty Publications

The invention provides a method for detecting the presence of Serpulina hyodysenteriae in a biological Sample, an oligonucleotide primer and an S. hyodysenteriae-specific oligonucleotide probe useful in that method, and an article of manufacture that contains the primers and/or probe. Also provided are an about 2.3-kb DNA fragment derived from genomic DNA of S. hyodysenteriae and encoding for an about 56 kDa polypeptide, a recombinant expression vector containing the DNA fragment, the 56 kDa polypeptide and a monoclonal antibody reactive with the peptide, and a method of assaying for antibodies reactive with the 56 kDa peptide.

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 …

Antiretroviral Cytolytic T-Lymphocyte Nonresponsiveness: Fasl/Fas-Mediated Inhibition Of Cd4+ And Cd8+ Antiviral T Cells By Viral Antigen-Positive Veto Cells, Robert F. Rich, William R. Green

Dartmouth Scholarship

C57BL/6 (H-2^b ) mice generate type-specific cytolytic T-lymphocyte (CTL) responses to an immunodominant K^b-restricted epitope, KSPWFTTL located in the membrane-spanning domain of p15TM of AKR/Gross murine leukemia viruses (MuLV). AKR.H-2^b congenic mice, although carrying the responder H-2^b major histocompatibility complex (MHC) haplotype, are low responders or nonresponders for AKR/Gross MuLV-specific CTL, apparently due to the presence of inhibitory AKR.H-2^b cells. Despite their expression of viral antigens and K^b, untreated viable AKR.H-2^b spleen cells cause dramatic inhibition of the C57BL/6 (B6) antiviral CTL response to in vitro stimulation with AKR/Gross MuLV-induced …