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Full-Text Articles in Medical Sciences

Effects Of Specific Alterations In Capsule Structure On Streptococcus Pneumoniae Capsule Assembly And Virulence, Bobbi Xayarath Jan 2007

Effects Of Specific Alterations In Capsule Structure On Streptococcus Pneumoniae Capsule Assembly And Virulence, Bobbi Xayarath

All ETDs from UAB

The polysaccharide capsules of Streptococcus pneumoniae represent the most important virulence determinant produced by this organism. Ninety-one different serotypes have been identified, but only a small number of these serotypes are responsible for most of the infections caused by S. pneumoniae. The reasons why certain serotypes predominate in infections over others are not well understood. One common serotype found in invasive diseases is type 2, however, it is unclear what characteristics of a type 2 capsule makes strains producing it virulent. The type 2 capsule consists of repeat units made of a backbone of Glc-Rha-Rha-Rha, with a side chain Glc-GlcUA …


The Role Of Cd5 In Experimental Autoimmune Encephalitomyelitis, Robert C. Axtell Jan 2007

The Role Of Cd5 In Experimental Autoimmune Encephalitomyelitis, Robert C. Axtell

All ETDs from UAB

The regulation of activation, differentiation and persistence of effector T-cells are critical for the development of Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. Until now, the function of CD5 was accepted to be a negative regulator of T-cell activation. This dissertation reports that CD5 has an addi-tional role in T-cell responses, which is to promote cell survival. Observations from EAE experiments revealed that mice deficient in CD5 exhibited decreased disease severity which was associated with the inability of activated T-cells to survive. Moreover, block-ing the engagement of CD5 in mice led to enhanced activation induced cell death …


Cd8+ T-Lymphocytes And The Control Of Cytomegalovirus Infection Of The Newborn Central Nervous System, Glenn Robert Burgner Bantug Jan 2007

Cd8+ T-Lymphocytes And The Control Of Cytomegalovirus Infection Of The Newborn Central Nervous System, Glenn Robert Burgner Bantug

All ETDs from UAB

Congenital HCMV infection of the developing brain is the leading viral cause of mental retardation and sensorineural hearing loss. To elucidate the pathogenesis of congenital HCMV CNS infections, we developed a small animal model of CMV infection where newborn Balb/c mice are peripherally inoculated with murine cytomegalovirus. In this model we observed transient deficits in cerebellar/hindbrain development as well as the recruitment of peripheral immune effector cells to the CNS parenchyma. CD8+ T-lymphocytes were the predominant mononuclear cellular infiltrates in the brain and immune-depletion of CD8+ cells resulted in increased viral genome copy numbers in the CNS. CD8+ T-lymphocytes exhibited …


Modulation Of Cell Signaling By Tomoregulins In Embryogenesis And Cancer, Paul William Harms Jan 2006

Modulation Of Cell Signaling By Tomoregulins In Embryogenesis And Cancer, Paul William Harms

All ETDs from UAB

Growth factor signals often regulate similar cellular processes both during embryogenesis and in adult homeostasis. Stringent control of these signals ensures proper embryonic development and correct cell physiology in mature individuals. Recently, a family of two members of Tomoregulin (or transmembrane protein with epidermal growth factor-like and two follistatin domains [TMEFF]) was found to interact with transforming growth factor-β (TGF-β) and ErbB signaling pathways, both of which are implicated in development and in cancer biology in the adult. The function as well as the mechanisms of TMEFFs in modulating these two signals has not been elucidated in detail. In this …


Increased Hexosamine Biosynthesis And Protein O-Glcnac Protect Isolated Rat Heart From Ischemia/Reperfusion Injury, Jia Liu Jan 2006

Increased Hexosamine Biosynthesis And Protein O-Glcnac Protect Isolated Rat Heart From Ischemia/Reperfusion Injury, Jia Liu

All ETDs from UAB

Increased levels of protein-associated O-linked N-acetylglucosamine (O-GlcNAc) have been correlated with increased tolerance to stress. Therefore the goal of this study was to determine whether enhanced flux through the hexosamine biosynthesis pathway (HBP), which leads to elevated levels of O-GlcNAc, increased the tolerance of the heart to ischemia and reperfusion (I/R). Hearts from male rats were isolated and perfused with Krebs-Henseliet buffer containing 5mM glucose, and global, no-flow ischemia was induced for 20min followed by 60 min reperfusion. 20 min pre-treatment with 10 mM glucosamine, which enters the HBP directly, significantly improved functional recovery and decreased cardiac Troponin I release …


Regulation Of Ss-Catenin By Gli1 In Epithelial Transformation, Xingnan Li Jan 2006

Regulation Of Ss-Catenin By Gli1 In Epithelial Transformation, Xingnan Li

All ETDs from UAB

Gli family members-mediated continuous Hedgehog (Hh) pathway activity plays a role in the growth of a number of human cancers, including the common malignancy of skin, basal cell carcinoma (BCC), and other highly aggressive tumor types. However, the mechanism by which Gli proteins act to promote the outgrowth of cancer in response to stimulation of Hh signaling is poorly understood. Identified as zinc finger transcriptional factors, the Gli family of proteins has been shown to be involved in multiple cellular processes through activating its target genes. Therefore, to study the function of Gli target genes is important for our understanding …


Klf4 Regulates Notch1 Expression And Signaling During Epithelial Transformation, Zhaoli Liu Jan 2006

Klf4 Regulates Notch1 Expression And Signaling During Epithelial Transformation, Zhaoli Liu

All ETDs from UAB

Notch1 and KLF4 function in the specification of epithelial cell fates, and each can act as a context-dependent oncogene or tumor suppressor. We report that KLF4 directly regulates transcription of Notch1 and that cleavage of full-length Notch1 to the active intracellular form, N1IC, is necessary for transformation by KLF4. Paradoxically, KLF4 suppresses canonical Notch1-CSL signaling by up-regulating Hairless, an antagonist of this pathway. Dominant-negative inhibitors of the canonical Notch1 signaling pathway do not block transformation of epithelial cells by KLF4, while they greatly reduce the efficiency of transformation by N1IC. Thus, N1IC can transform cells by two distinct mechanisms: the …


Kiss1 Metastasis Suppressor Secretion Is Required For Metastasis Suppression, Kevin T. Nash Jan 2006

Kiss1 Metastasis Suppressor Secretion Is Required For Metastasis Suppression, Kevin T. Nash

All ETDs from UAB

Failure to reduce the number of cancer deaths over the last 50 years is due to the inability to selectively target metastatic disease. Recently, the KISS1 metastasis suppressor has emerged as a promising molecular agent for the management of metastatic disease. Although KISS1 has been implicated in the regulation of the metastatic phenotype in human cancers and in in vivo mouse models, little is known about its mechanism. Recent evidence suggests that KISS1 is a neuropeptide that is processed and secreted to interact with its cognate receptor GPR54 in the hypothalamus to trigger puberty and maintain the reproductive state. However, …


Thermodynamic Consequences Of Dna Base Modifications And Ligand-Dna Interactions., Rachel Hutchins Graves Jan 2004

Thermodynamic Consequences Of Dna Base Modifications And Ligand-Dna Interactions., Rachel Hutchins Graves

All ETDs from UAB

The thermodynamic effects of alterations of the DNA duplex by DNA base modifications or ligand binding are investigated by a combination of spectrophotometric and calorimetric methods. Examination of the effects of substituent modification on the DNA binding energetics of the anticancer agent AAC (Y-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide) indicated that DNA binding affinities and energetics were enhanced upon substitution at the C5 position on the chromophore of the drug with a variety of chemical groups. A correlation between enthalpies of DNA binding and anticancer activity was evident.The impacts of DNA base modifications, including cytosine arabinoside, deaminated cytosine, and abasic sites, on the thermodynamics of …