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Characterization Of Host-Bacteria Interactions Contributing To Group B Streptococcus Colonization, Jennifer Marie Smith

Theses, Dissertations and Capstones

Group B streptococcus (GBS) is the leading cause of life-threatening bacterial infections during the first three months of life. GBS is also a frequent cause of maternal postpartum infections. Both types of infections stem from maternal vaginal and/or rectal colonization with GBS in the perinatal period. Limited information is available concerning how the colonization process occurs and what role the host immune system may play in the establishment of persistent colonization by GBS. The complex interactions between the immune system and GBS normally should end in clearance of the bacteria. However, since colonization by GBS occurs in a large number …

Mechanisms Counteracting Swelling In Brain Cells During Hyponatremia, Herminia Pasantes-Morales, Rodrigo Franco, Benito Ordaz, Lenin D. Ochoa

School of Veterinary and Biomedical Sciences: Faculty Publications

Water gain in the brain consequent to hyponatremia is counteracted by mechanisms that initially include a compensatory displacement of liquid from the interstitial space to cerebrospinal fluid and systemic circulation and subsequently an active reduction in cell water accomplished by extrusion of intracellular osmolytes to reach osmotic equilibrium. Potassium (K⁺), chloride (Cl^–), amino acids, polyalcohols, and methylamines all contribute to volume regulation, with a major contribution of ions at the early phase and of organic osmolytes at the late phase of the regulatory process. Experimental models in vitro show that osmolyte fluxes occur via leak pathways …

Microscopy Of Rat Thoracic Aorta In Chronic Ethanol Intake, Feral Öztürk, Ni̇gar Vardi, Nureddi̇n Cengi̇z, Mukaddes Eşrefoğlu, Ali̇ Otlu

Turkish Journal of Medical Sciences

The aim of this study was to determine the histological changes of the thoracic aorta in rats fed on alcohol for a period of 24 weeks. Twenty male Wistar rats were divided into two groups. The ethanol group (n=10) was fed on a modified liquid diet (MLD) containing 7.2% ethanol for 24 weeks. The control group (n=10) was fed on MLD without ethanol throughout the experiment. At the end of the 24 weeks, the carotid arteries of the rats were cannulated and their blood pressures were measured. Ethanol levels measured by using the NAD+/NADH enzyme-spectrophotometric method. Rats were killed by …

High-Resolution Physical Map For Chromosome 16q12.1-Q13, The Blau Syndrome Locus, Xiaoju Wang, Helena Kuivaniemi, Gina Bonavita, Charlene J. Williams, Gerard Tromp

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The Blau syndrome (MIM 186580), an autosomal dominant granulomatous disease, was previously mapped to chromosome 16p12-q21. However, inconsistent physical maps of the region and consequently an unknown order of microsatellite markers, hampered us from further refining the genetic locus for the Blau syndrome. To address this problem, we constructed our own high-resolution physical map for the Blau susceptibility region.

Results

We generated a high-resolution physical map that provides more than 90% coverage of a refined Blau susceptibility region. The map consists of four contigs of sequence tagged site-based bacterial artificial chromosomes with a total of 124 bacterial artificial …

Increased Production Of Pro-Inflammatory Cytokines And Enhanced T Cell Responses After Activation Of Human Dendritic Cells With Il-1 And Cd40 Ligand, Amy Wesa, Anne Galy

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Various microbial, inflammatory and immune signals regulate the activation of dendritic cells (DC), determining their ability to interact with naïve T cells and to produce cytokines that direct T cell development. In particular, CD40L and IL-1 cooperatively activate DC to secrete high levels of IL-12. The immuno-stimulatory capacity of such DC is otherwise not well-defined prompting further characterization of the effects of IL-1 and family members on DC activation in comparison with other pro-inflammatory stimuli.

Results

Human DC co-activated in vitro by CD40L and IL-1β expressed numerous cytokine genes including IL-12β, IL-23 p19, IL-1β, IL-1α, IL-1Ra, IL-10, IL-6, …

Search For Intracranial Aneurysm Susceptibility Gene(S) Using Finnish Families, Jane M. Olson, Sompong Vongpunsawad, Helena Kuivaniemi, Antti Ronkainen, Juha Hernesniemi, Markku Ryynã¤Nen, Lee-Lian Kim, Gerard Tromp

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci.

Methods

We previously estimated sibling relative risk in the Finnish population at between …

Small Glutamine-Rich Protein/Viral Protein U–Binding Protein Is A Novel Cochaperone That Affects Heat Shock Protein 70 Activity, Peter C. Angeletti, Doriann Walker, Antonito T. Panganiban

Nebraska Center for Virology: Faculty Publications

Molecular chaperone complexes containing heat shock protein (Hsp) 70 and Hsp90 are regulated by cochaperones, including a subclass of regulators, such as Hsp70 interacting protein (Hip), C-terminus of Hsp70 interacting protein (CHIP), and Hsp70-Hsp90 organizing factor (Hop), that contain tetratricopeptide repeats (TPRs), where Hsp70 refers to Hsp70 and its nearly identical constitutive counterpart, Hsc70, together. These proteins interact with the Hsp70 to regulate adenosine triphosphatase (ATPase) and folding activities or to generate the chaperone complex. Here we provide evidence that small glutamine-rich protein/viral protein U–binding protein (SGT/UBP) is a cochaperone that negatively regulates Hsp70. By “Far-Western” and pull-down assays, SGT/UBP …

Influence Of Protein Tyrosine Kinases On Cell Volume Change-Induced Taurine Release, Herminia Pasantes-Morales, Rodrigo Franco

School of Veterinary and Biomedical Sciences: Faculty Publications

Taurine efflux occurs in association with cell swelling in both hyposmotic and isosmotic conditions and during cell shrinkage in apoptotic death. Release occurs through a leak pathway, is largely Ca²⁺-independent and is sensitive to Cl^– channel blockers. Taurine efflux elicited by hyposmolarity is reduced or suppressed by tyrosine kinase blockers and increased by tyrosine phosphatase inhibitors. The specific kinases involved are still unknown and may be different in the various cell types. Non-receptor and scr-related protein kinases have been identified in some cells as elements that directly phosphorylate the taurine efflux pathway. Possible tyrosine kinase targets are …

Faculty Publications 2001, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 706 publications.

Staphylococcus Aureus Agr And Sara Functions Are Required For Invasive Infection But Not Inflammatory Responses In The Lung, Geoffrey Heyer, Shahryar Saba, Robert Adamo, William Rush, Grace Soong, Ambrose Cheung, Alice Prince

Dartmouth Scholarship

Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.

Expression Of Gus Gene In Tobacco (Nicotiana Tabacum) And Corn (Zea Mays) Using Dimboa-Resistant Agrobacterium Strains, Deepti Mohamalawari

Masters Theses & Specialist Projects

This thesis evaluates the ability of Agrobacterium tumefaciens strains resistant to the compound DIMBOA [2, 4-dihydroxy-7-methoxy-2h-l,4- benzoxazin-3(4H)-one] to infect corn. DIMBOA is a secondary plant metabolite and is believed to have antimicrobial properties and provides resistance to the plant against microbial infection. Agrobacteriummediated genetic transformation technique can be employed to genetically alter most dicotyledonous plant species. However, such transformation has been limited in monocotyledonous plants, especially corn. One of the factors responsible for this recalcitrance is the presence of DIMBOA in corn shoots. In this study, we proposed the use of DIMBOA- resistant strains of Agrobacterium tumefaciens, bearing binary plasmids …

Dextran-Methylprednisolone Succinate As A Prodrug Of Methylprednisolone: Plasma And Tissue Disposition, Xiaoping Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)–methylprednisolone succinate (DMP), was studied in rats. Single 5‐mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n  = 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0–96 h) or MP (0–2 h) injections. Concentrations of DMP and MP in samples were analyzed by size‐exclusion chromatography (SEC) and reversed‐phase high‐performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70‐kDa dextran resulted in 22‐, …

Characterization Of Seca-Sod Operon In Borrellia Burgdorferi., Tonya Lynn Nichols

Electronic Theses and Dissertations

Borrelia burgdorferi, the causative agent of Lyme disease, has been characterized as a microaerophilic spirochete. O2 consumption and utilization potentially yield reactive oxygen intermediates, such as superoxide, hydroxyl radicals, and hydrogen peroxide. This study investigated the expression of the sod gene, which encodes the only, identified oxidative defense mechanism in B. burgdorferi. Using primer extension analysis and RT-PCR, it was found that sod and secA are organized as a single transcriptional unit under the control of σ70-like promoter upstream of the secA open reading frame. Generally, gene expression decreases with increased distance from the promoter; however, secA expression was observed …

Molecular Studies Involving The Rev Protein Of Caprine Arthritis Encephalitis Virus And Visna Virus., Bridget Michele Graves

Electronic Theses and Dissertations

Caprine Arthirtis Encephalitis Virus (CAEV) and Visna Virus are two viruses of the lentivirus family. They encode three structural genes (gag, pol, and env) and two regulatory genes (rev and tat). The Rev protein regulates Gag, Pol and Env expression by transporting their mRNAs to the cytoplasm by binding to the RRE (Rev Response Element) found on their mRNAs. Previous studies have indicated that Rev may be toxic to transfected cells, overexpression of exogenous RREs or a better binding RRE can inhibit Rev activity and Rev-C (CAEV Rev) can trans-activate RRE-V (Visna Virus …

Map Kinases In Cynomolgus Monkey Sperm Hyperactivation, Emily Nicole Haynes

Biological Sciences Theses & Dissertations

Mammalian sperm exhibit characteristic motility patterns, termed hyperactivated (HA) motility, associated with completion of capacitation. In cynomolgus monkey (Macaca fascicularis) sperm, this HA motility is dependent in vitro upon the addition of exogenous cyclic nucleotide mediators, caffeine and dibutyryl-cyclic adenosine monophosphate (dbcAMP). Previous reports have shown protein tyrosine phosphorylation to be an integral component of this caffeine- and cAMP-stimulated HA motility. This study investigated the involvement of the mitogen-activated protein (MAP) kinase-signaling cascade. Semen specimens were collected in Talp-HEPES medium from proven breeders via electroejaculation. After washing, sperm were incubated in the presence and absence of the MAP …

The Chromokinesin Kid Is Necessary For Chromosome Arm Orientation And Oscillation, But Not Congression, On Mitotic Spindles, Aime A. Levesque, Duane A. Compton

Dartmouth Scholarship

Chromokinesins have been postulated to provide the polar ejection force needed for chromosome congression during mitosis. We have evaluated that possibility by monitoring chromosome movement in vertebrate-cultured cells using time-lapse differential interference contrast microscopy after microinjection with antibodies specific for the chromokinesin Kid. 17.5% of cells injected with Kid-specific antibodies have one or more chromosomes that remain closely opposed to a spindle pole and fail to enter anaphase. In contrast, 82.5% of injected cells align chromosomes in metaphase, progress to anaphase, and display chromosome velocities not significantly different from control cells. However, injected cells lack chromosome oscillations, and chromosome orientation …

A Novel Strategy Utilizing Co-Expression Of Murine Il-12 And Antisense Tgf-Pl Against H238 Tumor Formation, Craig A. Seheult

Loma Linda University Electronic Theses, Dissertations & Projects

Cytokines have a profound effect on immune modulation, thus playing a significant role in cancer gene therapy. A variety of human carcinomas secrete transforming growth factor-beta (TGF-β), a cytokine with potent immunosuppressive properties. Suppressing TGF-β could be a key to successfully combating malignancies, such as gliomas, mammary, and colon cancers, that over-express TGF-β. Conversely, interleukin-12 (IL-12) is a potent immunostimulatory cytokine capable of regulating T and NK cell-mediated cytotoxic responses (Trinchieri, 1994) during an anti-tumor response. Activation of the immune system with such immunostimulatory cytokines renders it inert to the suppressive effects of TGF-β. To better understand these processes our …

Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung

Dartmouth Scholarship

In searching the Staphylococcus aureus genome, we found several homologs to SarA. One of these genes, sarT, codes for a basic protein with 118 residues and a predicted molecular size of 16,096 Da. Northern blot analysis revealed that the expression of sarT was repressed by sarA and agr. An insertion sarT mutant generated in S. aureus RN6390 and 8325-4 backgrounds revealed minimal effect on the expression of sarR and sarA. The RNAIII level was notably increased in the sarT mutant, particularly in postexponential-phase cells, while the augmentative effect on RNAII was less. SarT repressed the expression of alpha-hemolysin, as determined …

Neuronal Cell Model And Methods Of Use Therefor, Craig S. Miller, Robert J. Danaher, Robert J. Jacob

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention provides, inter alia, a PC12 cell quiescently infected with a neurotropic virus. Preferred quiescently-infected neural cells are those wherein the neurotropic virus is a neurotropic herpes virus. Methods related to these and other materials are also provided.

Guanylyl Cyclase C Agonists Regulate Progression Through The Cell Cycle Of Human Colon Carcinoma Cells., Giovanni Mario Pitari, M D Di Guglielmo, J Park, S Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, …

Tetrafluoroazidoaniline And Method Of Making And Using The Same, Hans Peter Spielmann, Kareem A.H. Chehade

Molecular and Cellular Biochemistry Faculty Patents

The invention is directed to a novel compounds comprising 4-azidotetrafluoroaniline and the alkyl, acyl and sulfonamide derivatives thereof and to methods of making and using the same. The novel compounds are useful as a photoaffinity probe to study protein structure and function. Two methods for preparing 4-azidotetrafluoroaniline are disclosed, each employing a stable carbamate intermediate from which the 4-azidotetrafluoroaniline is derived.

Marek's Disease Virus (Mdv) Encodes An Interleukin-8 Homolog (Vil-8): Characterization Of The Vil-8 Protein And A Vil-8 Deletion Mutant Mdv, Mark S. Parcells, Su-Fang Lin, Robert L. Dienglewicz, Vladimir Majerciak, Dan R. Robinson, Hua-Chien Chen, Zining Wu, George R. Dubyak, Peter Brunovskis, Henry D. Hunt

Dartmouth Scholarship

Chemokines induce chemotaxis, cell migration, and inflammatory responses. We report the identification of an interleukin-8 (IL-8) homolog, termed vIL-8, encoded within the genome of Marek's disease virus (MDV). The 134-amino-acid vIL-8 shares closest homology to mammalian and avian IL-8, molecules representing the prototype CXC chemokine. The gene for vIL-8 consists of three exons which map to the BamHI-L fragment within the repeats flanking the unique long region of the MDV genome. A 0.7-kb transcript encoding vIL-8 was detected in an n-butyrate-treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is essentially abolished by cycloheximide and herpesvirus DNA polymerase inhibitor phosphonoacetate, indicating …

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …

Clumping Factor A Mediates Binding Of Staphylococcus Aureus To Human Platelets, Ian R. Siboo, Ambrose L. Cheung, Arnold S. Bayer, Paul M. Sullam

Dartmouth Scholarship

The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro. When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. We have now characterized the gene disrupted in PS12 and its function in platelet binding. DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two …

Evidence For Two Mechanisms Of Amino Acid Osmolyte Release From Hippocampal Slices, R. Franco, M. E. Torres-Marquez, H. Pasantes-Morales

School of Veterinary and Biomedical Sciences: Faculty Publications

A 30% decrease in osmolarity stimulated ³H-taurine, ³H-GABA and glutamate (followed as ³H-D-aspartate) efflux from rat hippocampal slices. ³H-taurine efflux was activated rapidly but inactivated slowly. It was decreased markedly by 100 μM 5-nitro-(3-phenylpropylamino) benzoic acid (NPPB) and 600 μM niflumic acid and inhibited strongly by tyrphostins AG18, AG879 and AG112 (25–100 μM), suggesting a tyrosine kinase-mediated mechanism. Hyposmolarity activated the mitogen-activated protein kinases (MAPK) extracellular-signal-related kinase-1/2 (ERK1/ERK2) and p38, but blockade of this reaction did not affect ³H-taurine efflux. Hyposmosis also activated phosphatidyl-inositide 3-kinase (PI3K) and its prevention by wortmannin (100 nM) essentially abolished …

Sars, A Sara Homolog Repressible By Agr, Is An Activator Of Protein A Synthesis In Staphylococcus Aureus, Ambrose L. Cheung, Katherine Schmidt, Brian Bateman, Adhar C. Manna

Dartmouth Scholarship

The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A …

Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros

Dartmouth Scholarship

To understand the role of white collar-2 in theNeurospora circadian clock, we examined alleles ofwc-2 thought to encode partially functional proteins. We found that wc-2 allele ER24 contained a conservative mutation in the zinc finger. This mutation results in reduced levels of circadian rhythm-critical clock gene products, frq mRNA and FRQ protein, and in a lengthened period of the circadian clock. In addition, this mutation altered a second canonical property of the clock, temperature compensation: as temperature increased, period length decreased substantially. This temperature compensation defect correlated with a temperature-dependent increase in overall FRQ protein levels, with the …

Assessment Of Immune System Involvement In Tourette Syndrome, Ashley Dawn Levine

Loma Linda University Electronic Theses, Dissertations & Projects

Tourette syndrome (TS) is currently hypothesized to be the result of genetic and immunological components. This study investigated whether TS subjects produce IgG and IgA antibodies that bind to caudate nucleus, hippocampus, frontal cortex, cerebellum, thalamus, globus pallidus interior, exterior and putamen. Thirty- two children (14 TS, 7 family control, and 11 non-family control) and thirty-nine adults (11 TS, 14 family control, and 14 non-family control) were studied. Immunofluorescent studies were performed on basal ganglia tissue using serum from TS children and their family members. Brain antigens were prepared as two fractions (supernatant and pellet) and used as targets for …

Arsenic Alters The Function Of The Glucocorticoid Receptor As A Transcription Factor, Ronald C. Kaltreider, Alisa M. Davis, Jean P. Lariviere, Joshua W. Hamilton

Dartmouth Scholarship

Chronic human exposure to nonovertly toxic doses of arsenic is associated with an increased risk of cancer. Although its carcinogenic mechanism is still unknown, arsenic does not directly cause DNA damage or mutations and is therefore thought to act principally as a co-mutagen, co-carcinogen, and/or tumor promoter. Previous studies in our laboratory demonstrated that effects of low-dose arsenic (III) (arsenite) on expression of the hormone-regulated phosphoenolpyruvate carboxykinase (PEPCK) gene were strongly associated with the glucocorticoid receptor (GR)-mediated regulatory pathway. We therefore examined specifically the effects of arsenite on the biochemical function of GR in hormone-responsive H4IIE rat hepatoma cells. Completely …

Unusual Presentation Of A Chondromyxoid Fibroma Of The Temporal Bone, Asuman Ni̇han Haberal, Banu Bi̇lezi̇kçi̇, Mehmet Coşkun, Nur Altinörs, Beyhan Demi̇rhan

Turkish Journal of Medical Sciences

No abstract provided.