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Interconversion Of The Specificities Of Human Lysosomal Enzymes, Ivan B. Tomasic 2010 University of Massachusetts Amherst

Interconversion Of The Specificities Of Human Lysosomal Enzymes, Ivan B. Tomasic

Masters Theses 1911 - February 2014

Fabry disease (FD) is an X-linked recessive lysosomal storage disorder (LSD) known to affect approximately 1 in every 40,000 males, and a smaller number of females. FD results from a deficiency of functional α-galactosidase (α-GAL), which leads to the accumulation of terminally α-galactosylated substrates in the lysosome. The predominant treatment is Enzyme Replacement Therapy (ERT), requiring the regular infusion of recombinant human α-GAL. More than half of individuals receiving ERT experience a range of adverse infusion reactions, and it has been reported that as many as 88% of patients receiving ERT develop neutralizing IgG antibodies against the drug.

In aim …


Identification Of Novel Antimalarials From Marine Natural Products For Lead Discovery, Stephenie M. Alvarado 2010 University of Central Florida

Identification Of Novel Antimalarials From Marine Natural Products For Lead Discovery, Stephenie M. Alvarado

Electronic Theses and Dissertations

An estimated 500 million cases of malaria occur each year. The increasing prevalence of drug resistant strains of Plasmodium in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. Therefore, discovery of new, inexpensive, and effective drugs are urgently needed to combat this disease. Marine biodiversity is an enormous source of novel chemical entities and has been barely investigated for antimalarial drug discovery. In an effort to discover novel therapeutics for malaria, we studied the antimalarial activities of a unique marine-derived peak fraction library provided by Harbor Branch Oceanographic …


Aging Effects On Acute Lung Inflammation After Burn Injury, Vanessa Nomellini 2010 Loyola University Chicago

Aging Effects On Acute Lung Inflammation After Burn Injury, Vanessa Nomellini

Dissertations

The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existant in young, healthy individuals. The studies outlined below use a murine model to determine the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals following burn injury. We hypothesized that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound. We found that neutrophils continue to accumulate in the lungs of aged …


Ethanol Impairs Mechanisms Of Macrophage Phagocytosis And Cytokine Production, John Karavitis 2010 Loyola University Chicago

Ethanol Impairs Mechanisms Of Macrophage Phagocytosis And Cytokine Production, John Karavitis

Dissertations

Extensive evidence indicates that alcohol (ethanol) consumption affects human health by altering normal physiological functions of the immune system. This study investigated the effect of a single in vivo exposure of macrophages to clinically relevant levels of ethanol (1.2 and 2.2 g/kg). Following 3 hour exposure, both doses of ethanol decreased ex vivo TNFα production by splenic and alveolar macrophages (AMs). Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNFα production at 3 and 6 hours post ethanol administration, as well as decreased IL-6 and IL-12 production after 6 hours, compared control treated groups. LPS or …


Functional And Phenotypical Analysis Of The Effects Of Aging On B Cells And Their Bone Marrow Microenvironment, Nicole May Ziegler 2010 Loyola University Chicago

Functional And Phenotypical Analysis Of The Effects Of Aging On B Cells And Their Bone Marrow Microenvironment, Nicole May Ziegler

Master's Theses

Aging impacts multiple organ systems, and specifically causes the immune system to lose its ability to efficiently fight off infections. Regarding immunity, aging research predominantly focuses on the adaptive immune system. B cells, which mediate the humoral arm of the adaptive immune system, develop throughout life in the bone marrow where microenvironmental `niches' are important. The bone marrow does not exactly `atrophy' with age; however, studies comparing young and old mice demonstrate an age-related change in the bone marrow B cell subpopulations.

The overall goal was to determine if femoral and sternum bone marrow have different plasma cell composition and …


An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy 2010 University of Nebraska-Lincoln

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IAs/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.


Method For Identification Of Virulence Determinants, Raul G. Barletta, Beth Harris 2010 Lincoln, NE

Method For Identification Of Virulence Determinants, Raul G. Barletta, Beth Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Disclosed are methods for the determination of virulence determinants in bacteria and in particular bacteria of the genus Mycobacterium. Also disclosed are compositions and methods for stimulating an immune response in an animal using bacteria and virulence determinants identified by the methods of the present invention.


Memory Cd8+ T Cell Differentiation, Joshua J. Obar, Leo Lefrancois 2010 University of Connecticut School of Medicine and Dentistry

Memory Cd8+ T Cell Differentiation, Joshua J. Obar, Leo Lefrancois

UCHC Articles - Research

In response to infection or effective vaccination, naive antigen-specific CD8+ T cells undergo a dramatic highly orchestrated activation process. Initial encounter with an appropriately activated antigen-presenting cell leads to blastogenesis and an exponential increase in antigen-specific CD8+ T cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in formation of both primary effector and long-lived memory cells. Current findings have emphasized the heterogeneity of effector and memory cell populations with the description of multiple cellular subsets based on phenotype, function, and anatomic location. Yet, only recently have we begun to dissect the underlying factors mediating the temporal control of the …


Phenotypical And Functional Analysis Of Peripheral T Cells In Foxn1 Transgenic Mice: Effects Of Aging, Paulette Krishack 2010 Loyola University Chicago

Phenotypical And Functional Analysis Of Peripheral T Cells In Foxn1 Transgenic Mice: Effects Of Aging, Paulette Krishack

Master's Theses

The thymus is the primary organ for the development and production of TCRαβ naive T cells. However, with increasing age thymic involution occurs, causing a decline in the output of naïve T cells. The decline in naïve T cell production results in a contraction in the peripheral naïve and expansion of the memory T cell pools. Not only are the production and compositions of peripheral T cells altered with age, T cell functions such as T cell proliferation and production of cytokines required for cell proliferation are also declined. Currently, it is not known if restoring the decline in the …


Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu 2010 Wayne State University

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …


Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita 2010 Wayne State University

Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita

Wayne State University Dissertations

Vibrio cholera, the causative agent of the severe diarreal illness cholera, uses a complex array of gene regulation to induce its virulence determinants. During the early stage of infection, and upon response to unknown signals, virulence genes are turned on. ToxT protein is the primary virulence gene transcription activator. Once ToxT is produced, it amplifies its own expression through an auto-regulatory loop and directly binds and activates expression of various virulence factors including the toxin-coregulated pilus (TCP) and cholera toxin (CT). During the late stage of infection, virulence genes are turned off and the bacteria escape the host to resume …


Tuberculosis: An Eight Year (2000-2007) Retrospective Study At The University Of Malaya Medical Centre (Ummc), Kuala Lumpur, Malaysia, Jamaiah Ibrahim 2010 University of Malaya

Tuberculosis: An Eight Year (2000-2007) Retrospective Study At The University Of Malaya Medical Centre (Ummc), Kuala Lumpur, Malaysia, Jamaiah Ibrahim

Jamaiah Ibrahim

This was an eight year (2000-2007) retrospective study of tuberculosis in patients admitted to the UMMC. A total of 131 cases were analyzed. Malays constituted the most cases, (43%), followed by Chinese (22%), Indians (17%) and others (18%). The majority of cases were within the 21-60 year old age group, which constituted 69.5% of the total. Males were more commonly affected (65%). Most cases were reported among Malaysians (83%). The majority of patients were unemployed (39%), followed by housewives (10%), laborers (9%), students (8%), shop assistants (7%), and other occupations (27%) The most common presenting complaints were prolonged productive cough, …


Cliff Swallows, Swallow Bugs, And West Nile Virus:, Larry Clark 2010 APHIS

Cliff Swallows, Swallow Bugs, And West Nile Virus:, Larry Clark

Larry Clark

The cliff swallow (Petrochelidon pyrrhonota) could play an important role in the transmission of West Nile virus (WNV) because of its breeding ecology, reservoir competence status, and potentially high natural exposure rates. Cliff swallows nest within colonies and their nests are occupied year-round by swallow bugs (Oeciacus vicarius), hematophagus ectoparasites that feed primarily on cliff swallows. These parasites are likely exposed to WNV while feeding on infectious blood of nesting cliff swallow adults and nestlings and thus, if competent vectors, could contribute to seasonal elevations in WNV transmission. In addition, swallow bugs remain within nests year-round and therefore could provide …


Prevalence Of Microsporidia In An Indigenous Orang Asli Community In Pahang, Malaysia, Tan Tian Chye 2010 University of Malaya

Prevalence Of Microsporidia In An Indigenous Orang Asli Community In Pahang, Malaysia, Tan Tian Chye

Tan Tian Chye

Microsporidia are ubiquitous parasites thought to be closely related to fungi. Their presence in the environment means that humans are frequently exposed to infection. Stool samples were collected from 151 indigenous villagers from the eastern state of Pahang in 2005. The samples were concentrated with water-ether sedimentation, stained with modified trichrome stain and examined under oil-immersion microscopy. Thirty-two specimens (21.2%) were positive for microsporidia. Microsporidia were observed as ovoid or rounded ovoid shapes measuring similar to 1 mu m, with a bright pink outline containing a central or posterior vacuole. PCR amplification with specific primers on microscopy-positive specimens amplified Encephalitozoon …


Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra 2010 University of Texas at El Paso

Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra

Open Access Theses & Dissertations

Hematological malignancies such as leukemia and lymphoma, can develop from aberrant changes in the cell signaling molecules to drive their uncontrolled cellular proliferation and differentiation. Activation, maturation, expansion and differentiation of T cells are critically regulated by the dynamics of various transcription factors activated by a variety of cytokines. Additionally, multiple effector molecules that mediate these T cells dependent signals include the JAK (Janus Kinase)-STAT (Signal transducer and activator of transcription) cascade. These signaling proteins are activated in response to a broad array of cytokines. Constitutively activated JAKs and STATs have been described in several T cell malignancies. A growing …


The Interplay Between Host Cells And The Human Pathogen Trypanosoma Cruzi: Role Of Toll-Like Receptors, Lilian Lie Nohara 2010 University of Texas at El Paso

The Interplay Between Host Cells And The Human Pathogen Trypanosoma Cruzi: Role Of Toll-Like Receptors, Lilian Lie Nohara

Open Access Theses & Dissertations

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected infectious disease that is becoming a world health concern. This obligate intracellular parasite employs a diversity of molecules and strategies to successfully invade a wide variety of mammalian cells and modulate host immune responses, which are essential features for completion of its life cycle in the host. The major plasma membrane antigens of T. cruzi infective trypomastigote forms are glycosylphosphatidylinositol (tGPI)-anchored mucin-like glycoproteins. Although previous studies demonstrated that the proinflammatory responses induced by tGPIs are mediated by Toll-like receptor (TLR) 2, the involvement of other TLRs …


Acanthamoeba Casstellanii : Intercellular Location Of Metacaspase, Danielle Maria Desser 2010 Marshall University

Acanthamoeba Casstellanii : Intercellular Location Of Metacaspase, Danielle Maria Desser

Theses, Dissertations and Capstones

Acanthamoeba castellanii, classified as a free living protist, are found in abundance in fresh water, filtered water, and soil, feeding upon bacteria in their environment. The pathogenic strain of this organism can cause either Acanathamoeba keratitis that targets eyes, or more rarely, granulomatous amoebic encephalitis, with immunocompromised individuals most at risk. Acanthamoeba castellanii are characterized by their two different stages: the trophozoite, which is the growing and dividing form, and the cyst form, which is the dormant stage. The cyst stage is highly resistant to harsh environmental conditions due to the double layer cell wall made largely of cellulose. It …


An Intervention To Prevent Symptoms Associated With Hepatitis C: A Pilot Study, Donna M. Zucker 2010 University of Massachusetts - Amherst

An Intervention To Prevent Symptoms Associated With Hepatitis C: A Pilot Study, Donna M. Zucker

Elaine Marieb College of Nursing Faculty Publication Series

The objectives of this study were to (a) pilot test instruments measuring fatigue and quality of life (QOL); (b) pilot test an exercise intervention; and (c) estimate the effect size of this intervention relative to completion of combination therapy, fatigue, QOL, and walking distance in 20 patients with chronic hepatitis C about to begin interferon alpha and ribavirin treatment. Alpha reliabilities for both the Schwartz Cancer Fatigue Scale and Hepatitis Quality of Life Questionnaire were moderately high. Power analyses of all outcome measures indicated a small effect size and sample size estimate of 30–40 per group to achieve power of …


Examination Of Homalometron Elongatum Manter, 1947 And Description Of A New Congener From Eucinostomus Currani Zahuranec, 1980 In The Pacific Ocean Off Costa Rica, Jessica H. Parker, Stephen S. Curran, Robin M. Overstreet, Vasyl V. Tkach 2010 University of Southern Mississippi

Examination Of Homalometron Elongatum Manter, 1947 And Description Of A New Congener From Eucinostomus Currani Zahuranec, 1980 In The Pacific Ocean Off Costa Rica, Jessica H. Parker, Stephen S. Curran, Robin M. Overstreet, Vasyl V. Tkach

Harold W. Manter Laboratory of Parasitology: Faculty and Staff Publications

Homalometron elongatum is reexamined using heat-killed material that was not subjected to pressure during fixation from Gerres cinereus collected from San Juan Harbor, Puerto Rico, U.S.A. The new material is compared with some paratype specimens and differs by having a much less variable forebody length, and a median rather than submedian genital pore. Tegumental spines reportedly cover the anterior end of the body but we observed tegumental spines covering the entire body surface in both the paratype and new material. Homalometron lesliorum n. sp. is described from Eucinostomus currani from the Pacific coasts of Costa Rica and Nicaragua. The new …


Robustness Of The Healthcare Utilization Results From The Rotavirus Efficacy And Safety Trial (Rest) Evaluating The Human-Bovine (Wc3) Reassortant Pentavalent Rotavirus Vaccine (Rv5), Robbin Itzler, Gary Koch, David O. Matson, Leif Gothefors, Pierre Van Damme, Mark J. DiNubile, Penny M. Heaton 2010 Old Dominion University

Robustness Of The Healthcare Utilization Results From The Rotavirus Efficacy And Safety Trial (Rest) Evaluating The Human-Bovine (Wc3) Reassortant Pentavalent Rotavirus Vaccine (Rv5), Robbin Itzler, Gary Koch, David O. Matson, Leif Gothefors, Pierre Van Damme, Mark J. Dinubile, Penny M. Heaton

Community & Environmental Health Faculty Publications

Background: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after …


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