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Articles 1561 - 1590 of 1904

Full-Text Articles in Life Sciences

Specificity Determinants Of Arma, A Ribosomal Rna Methyltransferase That Confers Antibiotic Resistance, Tamara Zarubica Sep 2010

Specificity Determinants Of Arma, A Ribosomal Rna Methyltransferase That Confers Antibiotic Resistance, Tamara Zarubica

Theses and Dissertations

Bacterial resistance to 4,6-type aminoglycoside antibiotics, which target the 30S ribosomal subunit, has been traced to the arm/rmt family of rRNA methyltransferases. These plasmid-encoded enzymes transfer a methyl group from S-adenosylmethionine to N7 of the buried G1405 in the aminoglycoside binding site of 16S rRNA in the 30S ribosomal subunit. Neither 16S rRNA alone nor intact 70S ribosome is an efficient substrate for armA methyltransferase. To more fully characterize this family of enzymes, xiii we have investigated the substrate requirements of ArmA. We determined the Mg2+ dependence of ArmA activity and found that the enzyme could recognize both translationally active …

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In Vivo Measurement Of Rat Skeletal Muscle Oxygen Consumption Following Brief Periods Of Ischemia With Reperfusion As Assessed By Phosphorescence Quenching Microscopy, William Nugent Aug 2010

In Vivo Measurement Of Rat Skeletal Muscle Oxygen Consumption Following Brief Periods Of Ischemia With Reperfusion As Assessed By Phosphorescence Quenching Microscopy, William Nugent

Theses and Dissertations

Brief periods of skeletal muscle ischemia (ischemic pre-conditioning) alter cellular metabolism in a way that confers protection over subsequent ischemic episodes. The mechanisms behind this effect have been studied indirectly through assays for the byproducts of ATP synthesis and in vitro studies of cellular signaling cascades and ROS generation. There have been no direct, in vivo assessments of the changes in respiration during reperfusion. We employed phosphorescence quenching microscopy in conjunction with a flow-arrest technique to assess the influences of external, pressure-induced 1- to 10-min focal ischemia on interstitial oxygenation (PISFO2) and the consumption of oxygen (VO2) in spinotrapezius muscles …

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Canopy Disturbance And Reproduction In Cornus Florida L., Daniel Carr Aug 2010

Canopy Disturbance And Reproduction In Cornus Florida L., Daniel Carr

Theses and Dissertations

This study examined aspects of local reproductive variation in the flowering dogwood (Cornus florida L.) coincident with recent differences in primary canopy architecture. The dogwood trees in this study were impacted by a hurricane that created numerous treefall gaps, which created fine scale heterogeneity in the primary canopy. Fine scale disturbances in a forest can result in changes for multiple members of the forest community, including the reproductive responses of the trees and interspecific pollination mutualisms. Previously determined differences in offspring genetic structure suggested that pollen movement among genetically unstructured maternal individuals was significantly impacted between open, or disturbed, canopy …

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Variation In Sound Production Of The Blue Catfish, Ictalurus Furcatus., Zachary Ghahramani Aug 2010

Variation In Sound Production Of The Blue Catfish, Ictalurus Furcatus., Zachary Ghahramani

Theses and Dissertations

The blue catfish, Ictalurus furcatus, is an invasive species introduced to Virginia in 1974 and is the largest catfish in the United States. Like other Ictalurids, they are capable of producing disturbance calls via stridulation of the pectoral spine. These sounds can be made in air and water, and catfish can be preyed upon by both aerial and underwater predators. I characterized these putative distress calls by recording them in air and in the fish’s natural habitat. Sounds exhibited a wide variation in acoustic parameters relative to fish ontogeny: larger fish produced higher amplitude sounds with lower frequency bands. Sweep …

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Effect Of Ph On The Transcriptional Profile Of Porphyromonas Gingivalis W83, Nathan Maietta Aug 2010

Effect Of Ph On The Transcriptional Profile Of Porphyromonas Gingivalis W83, Nathan Maietta

Theses and Dissertations

Porphyromonas gingivalis, a gram-negative, anaerobic bacterium, is widely recognized as a causative agent for periodontal disease. Despite sequencing of the complete genome, no research exists examining gene regulation response in P. gingivalis to shifts in pH. Previous studies have shown that P. gingivalis is capable of surviving in the variety of micro- environmental niches found within the oral cavity, including basic and acidic pH conditions. However, the underlying mechanisms of this survival are not well understood. This study examined P. gingivalis by comparing bacteria shocked at three acidic to neutral pH conditions (5.5, 6.5 and 7.0) to bacteria vii shocked …

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Discovery Of A Novel Ccr5 Antagonist As An Effective Therapeutic Agent For Prostate Cancer, Tasrif Ahmed Jul 2010

Discovery Of A Novel Ccr5 Antagonist As An Effective Therapeutic Agent For Prostate Cancer, Tasrif Ahmed

Theses and Dissertations

Previously, the CCR5 receptor was found to be a good target for treating prostate cancer (PCa). Dr. Yan Zhang’s laboratory designed several CCR5 antagonists, which were screened for their inhibitory effect on the growth and invasion of the M12, DU145 and PC-3 PCa cell lines. Primary in vitro screening showed one compound (Drug 17) significantly inhibited the proliferation of PCa cells at 1μM concentration, with a half-maximal inhibitory concentration of 237.68 nM. Further in vitro assays including a proliferation, cytotoxicity and invasion assay confirmed the inhibitory effect of drug 17. The physiological effect of drug 17 was tested by the …

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Contribution Of Nuceliec Acids On The Structure Of Recombinant Hepadnavirus Core Antigens, Maimuna Bruce Jul 2010

Contribution Of Nuceliec Acids On The Structure Of Recombinant Hepadnavirus Core Antigens, Maimuna Bruce

Theses and Dissertations

The Hepatitis B core antigen (HBcAg) has been proposed to be an ideal candidate for use as an adjuvant due to its immunogenicity, and tolerance to manipulations such as insertions of epitopes or covalent attachment of ligands. HBcAg is a complex macromolecule containing protein and nucleic acid. We investigated the effect of the removal and reconstitution of nucleic acids upon its structure. It’s been shown that the RNA content of hepadnavirus core antigens can be reduced significantly, but not be completely removed. Following removal of some of the RNA, antigens retain the ability to bind added nucleic acids, in particular, …

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Function And Regulation Of Matrix Metalloproteinase-1 In Glioblastoma Multiforme, Monika Anand Jul 2010

Function And Regulation Of Matrix Metalloproteinase-1 In Glioblastoma Multiforme, Monika Anand

Theses and Dissertations

Glioblastoma Multiforme (GBM) is an aggressive and fatal cancer of the brain. It is characterized with augmented morbidity and elusion to therapies due in part to the incessant infiltration and spread of tumor cells in normal brain. We investigated the function of Matrix metalloproteinase-1, an important enzyme noted to be responsible for invasion in other cancers, in GBM and its regulation by epidermal growth factor receptor (EGFR) signaling. Previous studies from our laboratory demonstrated elevated levels of MMP-1 in GBM. Further studies indicated the involvement of MMP-1 in GBM invasion. The GBM cell lines T98G, U251MG and U87MG were used …

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Characterization And Crystallization Of The Mycobacterium Tuberculosis Trmd, Zohal Hamidi Jul 2010

Characterization And Crystallization Of The Mycobacterium Tuberculosis Trmd, Zohal Hamidi

Theses and Dissertations

One third of the world’s population is affected by Tuberculosis (TB), a disease caused by infection with Mycobacterium tuberculosis (MtB). The emergence of multidrug-resistant MtB makes this disease a major public health concern. New agents are needed to treat TB infections in a manner that circumvents existing pathways of resistance. One strategy is to target the organism at the translational level by inhibiting vital modifications of RNA. One gene responsible for these modifications is the tRNA (guanosine-1)-methyltransferase, trmD, which has been shown to be essential in several bacteria. The eukaryotic and bacterial m1G methyltransferases are structurally dissimilar, making this enzyme …

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Role Of Xrcc3 In Acquisition And Maintenance Of Invasiveness Through Extracellular Matrix In Breast Cancer Progression, Siddharth Saini Jul 2010

Role Of Xrcc3 In Acquisition And Maintenance Of Invasiveness Through Extracellular Matrix In Breast Cancer Progression, Siddharth Saini

Theses and Dissertations

Acquisition of invasiveness through extracellular matrix is a crucial characteristic of transition to malignancy in the breast. It was previously shown that Polo-like kinase 1 (PLK-1), a mitotic kinase and genome stability regulator, is involved in acquisition of invasiveness in a breast cell model (HMT-3522 cell line) of pre-invasive to invasive transition. This and other data led to the suggestion that a new class of genes called GISEM for Genome Instability and Extracellular Matrix Invasiveness may exist. Previous lab data show that XRCC3 is found downregulated in progression from preinvasive to invasive phenotype. This led to the hypothesis that XRCC3 …

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Evolutionary Relationships In Afro-Malagasy Schefflera (Araliaceae) Based On Nuclear And Plastid Markers, Morgan Gostel Jul 2010

Evolutionary Relationships In Afro-Malagasy Schefflera (Araliaceae) Based On Nuclear And Plastid Markers, Morgan Gostel

Theses and Dissertations

The genus Schefflera is the largest in Araliaceae, with approximately 900 species. Recent studies have shown that Schefflera is polyphyletic and represents no fewer than five distinct clades, each corresponding to a specific geographic region including Asia, continental Africa and Madagascar, Melanesia, the Neotropics, and a small clade distributed throughout several islands in the insular Pacific Ocean. The Afro-Malagasy clade contains nearly 50 species distributed throughout tropical, sub-Saharan Africa, Madagascar, the Comoros, and the Seychelles islands. Previous studies have suggested that this group is monophyletic, identifying two smaller subclades within Afro-Malagasy Schefflera corresponding roughly to informal groups identified as “Meiopanax” …

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The Effects Of Hydrology And Vegetation On Microbial Community Structure And Soil Function In The Sediments Of Freshwater Wetlands, Christine Prasse Jul 2010

The Effects Of Hydrology And Vegetation On Microbial Community Structure And Soil Function In The Sediments Of Freshwater Wetlands, Christine Prasse

Theses and Dissertations

In wetland soils, hydrology is considered to be one of the primary factors shaping wetland function and microbial community structure, but plant-soil interactions are also important mechanisms affecting microbial nutrient transformations. The research presented here considered the interactive effect to describe how hydrology and the presence of plants alter the soil profile, the development of the bacterial community, and their associated functions. To achieve this goal, plots were established in three hydrologically-distinct regimes (Wet, Intermediate, and Dry) within a non-tidal freshwater wetland along the James River (Charles City County, Virginia). Inside each main plot, ten subplots were cleared of all …

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The Effect Of Cobalt Protoporphyrin And Cobalt Chloride On Heme Oxygenase Expression And Protection From Deoxycholate-Induced Apoptosis, Tina Lawson Jul 2010

The Effect Of Cobalt Protoporphyrin And Cobalt Chloride On Heme Oxygenase Expression And Protection From Deoxycholate-Induced Apoptosis, Tina Lawson

Theses and Dissertations

The inner surface of the stomach is lined by a mucous membrane known as the gastric mucosa. The integrity of the gastric mucosa is critical for protecting the stomach from the low pH and proteolytic environment within the lumen. Both clinically and experimentally, exposure of gastric mucosal cells to bile salts is known to cause injury. Bile salts present in duodenogastric reflux are thought to play a significant role in gastric ulcer formation and alkaline gastritis. In vitro, studies using physiologic concentrations of the secondary bile salt, deoxycholic acid, indicate that bile salts can induce apoptosis in cultured human gastric …

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Effects Of Alternative Prey As A Buffer To Predation Of Channel Catfish (Ictalurus Punctatus) By Largemouth Bass (Micropterus Salmoides), Shelley Nellis Jul 2010

Effects Of Alternative Prey As A Buffer To Predation Of Channel Catfish (Ictalurus Punctatus) By Largemouth Bass (Micropterus Salmoides), Shelley Nellis

Theses and Dissertations

Channel catfish have pectoral spines that lock to defend against gape-limited predators such as largemouth bass. Previous work indicated that spines increase survival of channel catfish exposed to bass but did not determine whether bass avoid catfish if less dangerous species are available. We presented bass with channel catfish and two alternatives, bluegill and goldfish, and compared order of ingestion, ingestion time, percent of successful strikes, and time spent chasing each prey species. We also presented the three species in a jar study that standardized position in the water column as well as in a net-pen study. The order of …

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Double-Strand Break Repair Mechanisms In Human Embryonic Stem Cells, Bret Adams Jul 2010

Double-Strand Break Repair Mechanisms In Human Embryonic Stem Cells, Bret Adams

Theses and Dissertations

Central to the progression of all organisms is the maintenance of a stable genome despite continuous insults arising from genotoxic and environmental stresses. Embryonic stem cells show promise for treatment of a variety of diseases as well as for providing normal human tissue to conduct scientific research. A major obstacle for their application is that genomic instability arises in stem cells after prolonged cell culture. The most detrimental form of DNA damage is the DNA double-strand break (DSB), which is managed by cells through complex mechanisms, designated the DNA damage response. There are two major types of DSB repair; homologous …

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Strategies To Employ Androstenediol To Reverse Steroid Inhibited Healing In A Rat Model Of Trauma, Francis Diskin Jul 2010

Strategies To Employ Androstenediol To Reverse Steroid Inhibited Healing In A Rat Model Of Trauma, Francis Diskin

Theses and Dissertations

Much of our current understanding regarding trauma, mechanisms of healing, and treatment strategies have evolved as a result of injuries suffered during armed conflict. While our understanding of these processes has advanced during and since these conflicts, treatment methods of traumatic wound healing have failed to progress significantly in the last forty years. The overall objective of this research was to test the hypothesis that the immune regulating hormone Androstenediol (AED) modulates the host’s immune system to promote wound healing under conditions where it has been inhibited by stress and infection. In an effort to characterize the effects of Androstenediol …

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Factors Influencing The Abundance, Community Composition And Activity States Of Bacterioplankton From The Tidal Freshwater James River, Catherine Luria Jul 2010

Factors Influencing The Abundance, Community Composition And Activity States Of Bacterioplankton From The Tidal Freshwater James River, Catherine Luria

Theses and Dissertations

Aquatic bacteria respond to changing environmental conditions through a variety of mechanisms including changes in abundance, shifts in community composition and variable activity states. In the tidal-freshwater James River, variation in bacterial abundance was linked to nutrient availability and autochthonous production with highest bacterial densities associated with low-nutrient, high-chlorophyll a conditions. Laboratory experiments revealed that bacterial growth rates were nutrient limited at the low-nutrient site, while co-limitation (nutrients, glucose, light) was apparent at the high nutrient site. Despite large differences in abundance, community composition was similar based on TRFLP and 16S rDNA pyrosequencing. Community similarity was lower among rRNA libraries …

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Pathogenic Role Of Phosphodiesterase Type 5 Upregulation In Cardiac Ischemia/Reperfusion Injury, Daniel Hobbs Jul 2010

Pathogenic Role Of Phosphodiesterase Type 5 Upregulation In Cardiac Ischemia/Reperfusion Injury, Daniel Hobbs

Theses and Dissertations

Phosphodiesterase Type 5 (PDE5) inhibitors are cardioprotective against ischemia/reperfusion (I/R) injury. However, it remains uncertain if I/R affects PDE5. We hypothesized that generation of reactive oxygen species (ROS) during I/R leads to upregulation of PDE5, which contributes to pathological changes following acute myocardial infarction (AMI). Adult male ICR mice were subjected to 30 minutes of in vivo or ex vivo I/R. To examine the role of ROS, a subset of hearts were perfused with 100 µM hydrogen peroxide (H2O2). Expression and activity of PDE5, pPDE5, and cGMP-dependent protein kinase (PKG) were measured by Western blots and spectrophotometric assay. The results …

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Molecular Mechanisms Involved Involved In The Interaction Effects Of Hcv And Ethanol On Liver Cirrhosis, Ryan Fassnacht Jul 2010

Molecular Mechanisms Involved Involved In The Interaction Effects Of Hcv And Ethanol On Liver Cirrhosis, Ryan Fassnacht

Theses and Dissertations

The leading causes of liver disease are Hepatitis C virus infection and chronic alcohol abuse. Alcohol accelerates liver disease in HCV but the mechanisms are poorly understood. The identification of molecular gene expression profiles on human liver tissue was performed using microarrays. Samples were obtained from alcoholic-cirrhotic, HCV-cirrhotic, HCV/alcohol-cirrhotic and control non-cirrhotic liver tissue. Probe set expression summaries were calculated using RMA. Probe set level linear models were fit where probe set expression was modeled by HCV status, alcohol status, and the interaction between HCV and Alcohol. HCV cirrhosis was associated with up-regulation of genes related to viral and immune …

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Novel Mechanism In Astrocyte Gene Regulation And Function, Sandeep Singh Jun 2010

Novel Mechanism In Astrocyte Gene Regulation And Function, Sandeep Singh

Theses and Dissertations

This dissertation sheds light on several novel mechanistic findings in astrocyte specific gene regulation and function by the NFI-X transcription factor which can be further extrapolated to astrocyte differentiation and glial tumor invasion. First, we cloned and analyzed human NFI-X3, a novel splice variant of the nfix gene, which contains a unique transcriptional activation (TA) domain completely conserved in primates. In contrast to previously cloned NFI-X1, overexpression of NFI-X3 potently activates NFI reporters, including GFAP reporter, in astrocytes and glioma cells. The expression of NFI-X3 is dramatically upregulated during the differentiation of neural progenitors to astrocytes and precedes the expression …

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Role Of Capsule In The Interaction Of Porphyromonas Gingivalis With Host, Amrita Singh May 2010

Role Of Capsule In The Interaction Of Porphyromonas Gingivalis With Host, Amrita Singh

Theses and Dissertations

Periodontal disease is a chronic oral disease that is triggered by bacteria. One of these bacteria is Porphyromonas gingivalis. Some strains of P. gingivalis produce capsule, however, so far the role of capsule in the interactions with host cells in P. gingivalis is not well understood. Here, we investigated the contribution of capsule to triggering host response as well as its protective role on bacterial internalization by host cells with subsequent killing. qRT-PCR analysis showed more upregulation of expression of various groups of genes in macrophages challenged with the non-capsulated strain than in those challenged with the capsulated one with …

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Signaling Pathways Coupled To Melatonin Receptor Mt1 In Gastric Smooth Muscle, Rashad Ahmed May 2010

Signaling Pathways Coupled To Melatonin Receptor Mt1 In Gastric Smooth Muscle, Rashad Ahmed

Theses and Dissertations

The Melatonin, a close derivative of serotonin, is involved in physiological regulation of circadian rhythms. In the gastrointestinal (GI) system, melatonin exhibits endocrine, paracrine and autocrine actions and is implicated in the regulation of GI motility. Generally, melatonin actions oppose the stimulatory actions of serotonin on motility. However, it is not known whether melatonin can also act directly on GI smooth muscle cells. The aim of the present study was to determine the expression of melatonin receptors in smooth muscle and identify their signaling pathways. Muscle cells were isolated from rabbit distal stomach by enzymatic digestion, filtration and centrifugation and …

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The Clinical Utility Of Cardiopulmonary Exercise Testing In Patients With Suspected Myocardial Ischemia, Sherry Pinkstaff May 2010

The Clinical Utility Of Cardiopulmonary Exercise Testing In Patients With Suspected Myocardial Ischemia, Sherry Pinkstaff

Theses and Dissertations

Heart disease is a major cause of morbidity and mortality in the United States with coronary artery disease (CAD) representing more than half of all cardiovascular events. Stable patients presenting with symptoms suggestive of CAD are likely to undergo either an exercise ECG and/or imaging study as a first line diagnostic assessment. A cardiopulmonary exercise test (CPX) is an ECG stress test plus ventilatory gas analysis. Recently CPX has been used to detect exercise-induced myocardial ischemia suggestive of underlying CAD. Currently there are a number of diagnostic tests available for the identification of CAD with the most widely used being …

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Opioid Addiction And Pregnancy: Potential Effects Of Substitution Therapies On Developmental Myelination, Andrew Eschenroeder May 2010

Opioid Addiction And Pregnancy: Potential Effects Of Substitution Therapies On Developmental Myelination, Andrew Eschenroeder

Theses and Dissertations

While most cells of the central nervous system (CNS) express opioid receptors, the role of the endogenous opioid system in CNS development remains poorly understood. Identification of opioid functions during brain maturation is particularly crucial in light of the increasing trend in opioid abuse and the use of opioid drugs during pregnancy. New substitution therapies in pregnant opioid addicts include buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor antagonist. However, while clinical studies demonstrated buprenorphine efficacy in reducing neonatal withdrawal symptoms, there is a lack of information on the potential effects of this drug on brain development. …

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Effect Of Hyaluronidase Treatment On The Structural Integrity Of The Endothelial Glycocalyx Layer, Kristin Simmons May 2010

Effect Of Hyaluronidase Treatment On The Structural Integrity Of The Endothelial Glycocalyx Layer, Kristin Simmons

Theses and Dissertations

The endothelial glycocalyx plays an important role as part of the permeability barrier between the blood and the interstitium. In this study, we used different sized fluorescently labeled dextran molecules to determine the size of the macromolecular exclusion zone in capillaries. The width of the exclusion zone was calculated as one half the difference between the anatomic luminal diameter, as determined by transillumination, and the width of a fluorescent dextran column. During the first hour after systemic injection of labeled dextrans, neither 70 kDa dextran (Dextran 70) nor 500 kDa dextran (Dextran 500) labeled with the anionic fluorescein isothiocyanate (FITC) …

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A Computational Biology Approach To The Analysis Of Complex Physiology: Coagulation, Fibrinolysis, And Wound Healing, Nathan Menke May 2010

A Computational Biology Approach To The Analysis Of Complex Physiology: Coagulation, Fibrinolysis, And Wound Healing, Nathan Menke

Theses and Dissertations

The birth of complexity research derives from the logical progression of advancement in the scientific field afforded by reductionist theory. We present in silico models of two complex physiological processes, wound healing and coagulation/fibrinolysis based on two common tools in the study of complex physiology: ordinary differential equations (ODE) and Agent Based Modeling (ABM). The strengths of these two approaches are well-suited in the analysis of clinical paradigms such as wound healing and coagulation. The complex interactions that characterize acute wound healing have stymied the development of effective therapeutic modalities. The use of computational models holds the promise to improve …

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A Novel Role Of Sirt1 In Sildenafil Induced Cardioprotection In Mice, Mona Shalwala May 2010

A Novel Role Of Sirt1 In Sildenafil Induced Cardioprotection In Mice, Mona Shalwala

Theses and Dissertations

Phosphodiesterase-5 inhibitor, sildenafil (SIL) protects against myocardial ischemia/reperfusion (I-R) injury. We hypothesized that SIL-induced protection may be mediated through activation of SIRT1, an enzyme which deacetylates proteins involved in cellular stress response. Adult male ICR mice were treated with SIL (0.7mg/kg ip), Resveratrol (RSV) (5mg/kg ip) (positive control), or saline (0.2 ml ip). The hearts were harvested 24 h later and homogenized for SIRT1 activity analysis. Both SIL and RSV increased cardiac SIRT1 activity (P<0.001) as compared to Saline. Adult mouse ventricular cardiomyocytes pre-treated with either SIL or RSV (1µM) in vitro also upregulated SIRT1 activity (P<0.05). SIL also reduced infarct size following 30 min. ischemia and 24 h reperfusion in vivo. Sirtinol (5mg/kg in 10% DMSO, ip), a SIRT1 inhibitor abolished the infarct-limiting effect of SIL and RSV (P<0.001). In conclusion, activation of SIRT1 by SIL plays an essential role in cardioprotection against I-R injury.

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Role Of Neutrophils In Enhancing Vascular Reactivity To Angiotensin Ii In Preeclampsia, Nikita Mishra May 2010

Role Of Neutrophils In Enhancing Vascular Reactivity To Angiotensin Ii In Preeclampsia, Nikita Mishra

Theses and Dissertations

Women with preeclampsia have enhanced vascular reactivity to Angiotensin II (Ang II) and extensive vascular infiltration of neutrophils. The primary mechanism to enhance vessel reactivity is RhoA kinase that phosphorylates MYPT1 to inhibit myosin light chain (MLC) phosphatase. Therefore, MLCs remain phosphorylated and increase sensitivity to calcium. Neutrophils release reactive oxygen species (ROS), which can activate this pathway, so we hypothesized that neutrophils would enhance vessel reactivity to Ang II. Omental vessels from normal pregnant women were used to study vascular reactivity. Ang II dose response (0.001-10µM) was significantly enhanced with perfusion of neutrophils (<2000/mm3, activated with IL-8) or ROS. Addition of superoxide dismutase (SOD)/Catalase to quench ROS or 3µM Y-27632, a specific RhoA kinase inhibitor, blocked enhancement. Vascular smooth muscle expression of pMYPT1 and pMLC in cell culture was significantly increased by neutrophils or ROS. The increase was prevented by Y-27632. RhoA kinase activity assay showed a 3-fold increase in RhoA kinase activity in omental vessels treated with ROS. Similarly, ROS also enhanced vessel reactivity to another vasoconstrictor, norepinephrine, via RhoA kinase. In preeclamptic women, increased neutrophil infiltration is associated with increased vascular expression and production of matrix metalloproteinase-1 (MMP-1). MMP-1 activates protease activated receptor-1 (PAR-1), which could cause endothelial endothelin-1 release, so we considered a novel hypothesis that MMP-1 might cause vasoconstriction and enhance vessel reactivity to Ang II via PAR-1. Omental vessels perfused with activated MMP-1 (0.025-25ng/ml) showed dose-dependent vasoconstriction. Perfusion of activated MMP-1 (2.5ng/ml) significantly enhanced dose response to angiotensin II. MMP-1 mediated vasoconstriction and enhanced vessel reactivity to Ang II was abolished by co-perfusion of 10µM SCH-79797, a specific PAR-1 blocker, and by 5µM BQ-123, a specific endothelin-1 type A receptor blocker. These data are the first to show that activated neutrophils enhance vascular reactivity to Ang II via ROS and the RhoA kinase pathway. They are also the first to show that MMP-1 induces vasoconstriction and enhances vessel reactivity to Ang II. Thus, vascular neutrophil infiltration leading to ROS and MMP-1 generation could be an important mechanism for hypertension in preeclampsia.

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Long-Term Spatial And Temporal Variability Of Benthic Macroinvertebrate Communities: Implications For Bioassessment Of Lotic Systems, Eve O'Connor May 2010

Long-Term Spatial And Temporal Variability Of Benthic Macroinvertebrate Communities: Implications For Bioassessment Of Lotic Systems, Eve O'Connor

Theses and Dissertations

The structure and composition of benthic macroinvertebrate communities can vary spatially and over time. Spatial and temporal variation along a stream has many implications for population and community dynamics, which may influence bioassessment programs. I examined variability in the benthic community of eight streams within the Polecat Creek, Virginia watershed. These streams vary in size from 1st to 4th order. The streams were sampled once every season for eleven years using standard bioassessment protocols. Macroinvertebrates were sampled from both sediment and submerged wood habitats at each site. The coefficient of variation (CV) was used to quantify among season, among year …

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The Development Of A Novel Multi-Dimensional Product For Wound Healing Applications, Necrisha Roach May 2010

The Development Of A Novel Multi-Dimensional Product For Wound Healing Applications, Necrisha Roach

Theses and Dissertations

A characteristic feature of chronic wounds is a prolonged inflammatory response as well as susceptibility to infection. Studies have shown that during the inflammatory response, there is a significant increase in the levels of neutrophil-derived enzymes. The purpose of this work was to determine whether the anionic macromolecule polystyrene sulfonate (PSS) and five of its salt forms, namely PSS-calcium, PSS-chlorhexidine, PSS-doxycycline, PSS-glutathione and PSS-silver are able to inhibit the activity of three of the enzymes whose levels are elevated in chronic wounds: elastase, cathepsin G and myeloperoxidase. In addition to the enzyme inhibition study, the various formulations’ antimicrobial properties were …

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