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Articles 3421 - 3450 of 5384

Full-Text Articles in Medicine and Health Sciences

Association Between Obesity And Depression And Anxiety Disorders: Results From The 2008 National Health Interview Survey, Monica Gaidhane Dec 2009

Association Between Obesity And Depression And Anxiety Disorders: Results From The 2008 National Health Interview Survey, Monica Gaidhane

Theses and Dissertations

Introduction: Obesity is one of the most important medical problems in the U.S. and is considered to be an epidemic with over 30% of the population being obese. Obesity is associated with increased risk of hypertension, diabetes, cardiovascular diseases, certain cancers and a shorter life expectancy. Recent studies have shown that higher BMI levels are also significantly associated with several lifetime mental disorders such as major depressive disorder, anxiety disorders as well as panic attacks and panic disorders. Purpose: The purpose of this study was to quantify the extent to which higher BMI increased the likelihood of Depression, Anxiety Disorder …

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Intimate Partner Violence And Pregnancy: Data From The Chicago Women's Health Risk Study, Anne Zehner Dec 2009

Intimate Partner Violence And Pregnancy: Data From The Chicago Women's Health Risk Study, Anne Zehner

Theses and Dissertations

Background: Intimate partner violence (IPV) during pregnancy increases the risks of adverse outcomes for both mothers and their unborn children, including maternal and fetal death. However, more research is needed to determine if IPV increases in frequency or severity during pregnancy and to determine what the risk factors are for IPV during pregnancy. Objectives: To use data from the Chicago Women’s Health Risk Study to determine (1) if abuse is more prevalent during the pregnancy period, 2) if abuse during the pregnancy period increases in frequency or severity, 3) if pregnant women who are abused are at increased risk for …

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Histone Deacetylase Inhibitors And Innate Immunity In Septic Shock, Joseph Bertsche Dec 2009

Histone Deacetylase Inhibitors And Innate Immunity In Septic Shock, Joseph Bertsche

Theses and Dissertations

Innate immunity depends on pattern recognition receptors, which recognize pathogen associated molecular patterns (PAMPS), such as Toll-like receptor 4 (TLR4), which detects the gram-negative bacterial toxin, lipopolysaccharide. Engagement of TLR4 by LPS sets off a cascade ending in the activation of pro-inflammatory cytokines and interferon-β (IFN-β) which alerts the host to the infection. However, these responses can be mal-adaptive, especially in the context of bacterial sepsis, where a "cytokine storm" results in death of the host. Pharmacological modulation of these responses may therefore be a promising treatment modality. Inhibition of classic pro-inflammatory cytokines such as IL-1β and TNF-α has been …

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Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett Dec 2009

Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett

Theses and Dissertations

The opioid receptors and their endogenous ligands have long been implicated in a variety of traits including addiction, impulsive behaviors and substance dependence. Using phenotypic measurements collected from the IASPSAD, data from a latent class analysis and data from a SNP array and additional genotyping assays, association and regression tests were performed to determine the effects of common SNPs encoded in the genes of the opioid receptors and ligands on various traits relating to alcohol dependence. Although only one SNP can be reported as significant for substance dependence within alcoholics, there were a few results approaching significance that may offer …

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Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith Nov 2009

Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith

Theses and Dissertations

EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 …

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Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney Nov 2009

Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney

Theses and Dissertations

The chemokine receptor CCR5 has been implicated in the pathogenesis of prostate cancer. A novel natural product, anibamine, was isolated and found to be a micromolar inhibitor of the receptor. Anibamine was used as a new anti-prostate cancer lead compound. To discover the pharmacophore, analogs of anibamine were designed using the “deconstruction-reconstruction-elaboration” approach and synthesized. The establishment of a stereoselective route to only one isomer was explored, to increase yield and eliminate elaborate purification procedures. Analogs were found to have anti-prostate cancer activity at levels higher than the parent compound. The molecular modeling studies of the deconstructed analogs indicate that …

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Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez Nov 2009

Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez

Theses and Dissertations

The neisserial transferrin binding proteins (Tbps) comprise a bipartite system for iron acquisition from human transferrin. TbpA is a TonB-dependent outer membrane protein that forms the pore for iron internalization. TbpB is a surface-exposed lipoprotein that makes the iron-uptake process more efficient. Previous studies have shown that the genes encoding these proteins are arranged in a bicistronic operon, with the tbpB gene located upstream of tbpA. The operon is under the control of the ferric uptake regulator (Fur) protein. However, promoter elements necessary for the regulation of the operon have not been experimentally defined. In this study, putative regulatory motifs …

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Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia Nov 2009

Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia

Theses and Dissertations

Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task …

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Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah Nov 2009

Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah

Theses and Dissertations

Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.

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Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins Nov 2009

Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins

Theses and Dissertations

This thesis investigates two separate features of nonhomologous end-joining (NHEJ) DNA repair: end processing, and DNA repair kinase signaling. DNA end processing was investigated in a mouse model of hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), a congenital neurodegenerative disease. SCAN1 is caused by a homozygous H493R mutation in the active site of tyrosyl-DNA phosphodiesterase (TDP1). To address how the H493R mutation elicits the specific pathologies of SCAN1 and to further elucidate the role of TDP1 in processing DNA end modifications, we generated a Tdp1 knockout mouse and characterized their behavior and specific repair deficiencies in extracts of embryonic fibroblasts …

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Denitration In Colonic Smooth Muscle, Seemab Malick Nov 2009

Denitration In Colonic Smooth Muscle, Seemab Malick

Theses and Dissertations

Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that …

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Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones Nov 2009

Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones

Theses and Dissertations

The primary aims of this study were to examine acquired genetic and epigenetic changes that occur in individuals with increasing age and to determine how these changes are influenced by genetic/environmental factors. Acquired genetic changes were assessed by determining the frequency and chromosomal contents of spontaneously occurring micronuclei in identical and fraternal twins. A total of 115 individuals (48 twin pairs and 19 singletons) were evaluated, ranging in age from 7 to 85 years. As expected, micronuclei frequencies, which are indicative of genomic damage, significantly increased with age (p<0.0001, r=0.446). The majority of micronuclei (32%) contained sex chromosomes and the frequency of sex chromosome-bearing micronuclei significantly increased with age (p<0.0001). The frequency of autosome-containing micronuclei was not significantly influenced by age or gender. However, some autosomes were seen more (chromosomes 4, 8, and 9) or less (chromosomes 17 and 22) frequently than expected by chance (p<0.05). An evaluation of the numerical contents of the sex chromosome-containing micronuclei and their corresponding binucleates showed that the majority of the binucleates had an abnormal chromosomal complement (either hypodiploid or hyperdiploid), with the subset of binucleates having a normal chromosomal complement decreasing with age for both the Y chromosome in males and the X chromosome in females. Model fitting, implemented in Mx, showed the variation in the frequency of micronuclei to be best explained by either additive genetic and unique environmental components, or common and unique environmental factors. Specific environmental exposures and health conditions that were shown to influence micronuclei frequencies, included: multivitamins, leafy green vegetables, fruit, vitamin E supplements, arthritis, heart disease, allergies, and alcohol. To assess acquired epigenetic changes, global methylation profiles of two identical twin pairs were compared and found to differ, indicating that individuals do develop alterations in their methylation profiles with age. Furthermore, the twin pair having a significant difference in their micronuclei frequencies and environmental exposures had more differences in their methylation pattern compared to the twin pair whose micronuclei frequencies and environmental factors did not differ. Overall, genetic and epigenetic changes were shown to occur with age and to be influenced by genetic and lifestyle factors.

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Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman Oct 2009

Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman

Theses and Dissertations

There is conflicting data on the effects of statins on cerebral vasospasm and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. In this retrospective cohort study, patients were divided into those who received pravastatin (PRAV group) 40mg/d and those who did not (NP group). Data were analyzed using multivariate logistic regression. Eighty-one patients met inclusion criteria. There was a statistically significant decreased in the incidence of vasospasm in the PRAV group; however, this association did not retain significance after adjusting for WFNS, race, elevated WBC, and clipping (59% PRAV vs. 88% NP, p=0.08). There was no statistically significant difference in …

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Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti Sep 2009

Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti

Theses and Dissertations

Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …

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Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen Sep 2009

Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen

Theses and Dissertations

Understanding the genetic foundations of schizophrenia and the resultant symptom manifestations is an important step as we work toward development of new prevention and treatment strategies. This work has sought better understanding of this disease through use of three subject cohorts and two studies using simulated data exploring features of complex disease. First, we probed the symptoms of schizophrenia in subjects of African and European ancestry drawn from the Genetic Association Information Network (GAIN) schizophrenia study and found significant differences between groups, particularly in affective symptoms. The genetic basis of symptom variation was then explored in a selection of candidate …

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Effect Of Renin Angiotensin System Inhibition On Cardiovascular Sequelae In Elderly Hypertensive Patients With Insulin Resistance, Hala Zreikat Sep 2009

Effect Of Renin Angiotensin System Inhibition On Cardiovascular Sequelae In Elderly Hypertensive Patients With Insulin Resistance, Hala Zreikat

Theses and Dissertations

Background: Insulin resistance may play a pathogenic role in cardiovascular disease (CVD). Resistance to insulin has been associated with obesity, hypertension, and abnormal glucose and lipid metabolism. The constellation of these features among insulin resistant subjects has been called the metabolic syndrome. Prevalence of the metabolic syndrome increases with age and is most common in the elderly. Different criteria have been proposed to define the metabolic syndrome (ATP, WHO, AACE, EGIR). Current management of metabolic syndrome focuses on the specific risk factors that the patient may have without targeting the underlying insulin resistance. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin …

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Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow Sep 2009

Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow

Theses and Dissertations

Traumatic spinal cord injury (SCI) is a physically debilitating, emotionally devastating, financially costly, and life-changing condition that afflicts more than 1,000,000 people in the United States alone. Owing to the characteristic neuropathology and low regenerative capacity of the central nervous system, many victims of SCI are left permanently paralyzed. Though the tissue damage caused by the initial insult almost certainly cannot be reversed, intensive research in recent years to elucidate the cellular and molecular events that follows has provided new grounds for optimism. Accordingly, in this dissertation, we present a number of potential treatment strategies aimed to address some of …

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Exploring The Stress Response In New Army Nurses, Laureen Otto Sep 2009

Exploring The Stress Response In New Army Nurses, Laureen Otto

Theses and Dissertations

The study of stress is limited in professional nursing, but it is nearly non-existent in professional military nursing. The purpose of this study was to explore the relationships among psychological, environmental, biological and demographic factors of stress in new Army nurses during the Army Medical Department’s 8-week Officer Basic Leadership Course (OBLC). Using a descriptive prospective, correlational repeated measures design, 33 study participants completed two psychological stress measures (Perceived Stress Scale [PSS] and the Impact of Event Scale – Revised[IES-R]), an environmental measure (Life Experiences Survey [LES]), a biologic measure (salivary cortisol) and a demographic questionnaire at three different time …

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Identification Of Clinical, Laboratory And Genetic Covariates For Pharmacokinetics, Efficacy And Toxicity Of Sorafenib In Patients With Solid Tumors, Lokesh Jain Aug 2009

Identification Of Clinical, Laboratory And Genetic Covariates For Pharmacokinetics, Efficacy And Toxicity Of Sorafenib In Patients With Solid Tumors, Lokesh Jain

Theses and Dissertations

The goal of this research work was to understand the clinical-pharmacology based treatment approaches for sorafenib. Treatment with sorafenib is associated with high inter-patient variability in pharmacokinetic exposures, efficacy and toxicity. We explored the demographic, laboratory, clinical and pharmacogenetic factors to elucidate the sources of variability. In addition, we examined the impact of pharmacogenetic variation in VEGFR2, an important mediator of the VEGF pathway, on risk of prostate cancer. To support these investigations, (mainly single-dose) pharmacokinetic, pharmacogenetic, efficacy and toxicity information were collected from patients with solid tumors, enrolled in five phase I / II clinical trials at National Cancer …

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Adenosine Dimethyltransferase Ksga: Biochemical Characterization Of The Protein And Its Interaction With The 30s Subunit, Pooja Desai Aug 2009

Adenosine Dimethyltransferase Ksga: Biochemical Characterization Of The Protein And Its Interaction With The 30s Subunit, Pooja Desai

Theses and Dissertations

Ribosomes form the core of the protein biosynthesis machinery and are essential to life. Ribosome biogenesis is a complex cellular process involving transcription of rRNA, pre-rRNA processing, rRNA modification and simultaneous assembly of ribosomal proteins. RNA nucleotide modification is observed in all domains of life. While there is enormous conservation of ribosome structure, very few post-transcriptional rRNA modifications have been conserved throughout evolution. A notable example of such rare conservation is the dimethylation of two adjacent adenosines in the 3’-terminal helix, a highly conserved region of the small subunit rRNA. Enzymes that carry out these dimethylations are equally conserved and …

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Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi Aug 2009

Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi

Theses and Dissertations

P450s are heme containing enzymes which affect oxidation of substrates via catalytic intermediates having transient lifetimes. These oxidative catalytic intermediates are formed by a sequential interplay of electrons and protons at the active site of the enzyme bearing molecular dioxygen. The proton transfer to the active site from bulk solvent is coordinated by an “acid-alcohol” pair of active site residues which are conserved in all P450s. Sterol 14α-demethylases (CYP51) are P450 enzymes which catalyze oxidative deformylation of lanosterol in the cholesterol/ergosterol biosynthetic pathway. Both cholesterol and ergosterol are important regulators of membrane fluidity. CYP51 differs from other P450s in that …

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Age-Related Differences In In-Vitro Sensitivity To Inhibition Of Human Red Blood Cell Acetylcholinesterase And Plasma Butyrylcholinesterase By The Cholinesterase Inhibitors Physostigmine (Phys), Pyridostigmine (Pyr), Donepezil (Don) And Galantamine (Gal), David Lee Jul 2009

Age-Related Differences In In-Vitro Sensitivity To Inhibition Of Human Red Blood Cell Acetylcholinesterase And Plasma Butyrylcholinesterase By The Cholinesterase Inhibitors Physostigmine (Phys), Pyridostigmine (Pyr), Donepezil (Don) And Galantamine (Gal), David Lee

Theses and Dissertations

Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disorder, characterized clinically by a progressive loss of memory, cognitive function, ability to care for oneself and psychiatric symptoms. First-line agents for the treatment of AD are ChE inhibitors (DON, GAL), whose modest clinical efficacy and the high incidence of dose-limiting toxicities limit their clinical utility. In addition to AD, ChE inhibitors (PYR) are used for other medical conditions, such as myasthenia gravis (MG). Furthermore, ChE inhibitors (PYR) are used by military personnel prophylactically if impending exposure to chemical warfare agents, e.g., soman, is suspected. The purpose of this research project was …

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To Evaluate The Level Of Agreement Between Two Self-Reported Medication Adherence Scales And Prescription Refill Records In Older Adults, Priyanka Kakad Jul 2009

To Evaluate The Level Of Agreement Between Two Self-Reported Medication Adherence Scales And Prescription Refill Records In Older Adults, Priyanka Kakad

Theses and Dissertations

Objective: To evaluate the level of agreement between two self-reported medication adherence scales and prescription refill records in older adults. Design: Cross-sectional study Setting: Imperial Plaza; a retirement community located in Richmond, Virginia. Participants: 32 independent-living older adults, taking anti-hypertensive medications and filling their prescriptions at on-site Plaza Professional Pharmacy were recruited in the study. Methods: Participants’ 6 months refill records were obtained and Medication Possession Ration (MPR) was calculated. Participants were interviewed using Morisky Medication Adherence Scale (MMAS) & Brief Medication Questionnaire (BMQ). Kappa statistics was used to evaluate the level of agreement. Results: Poor level of agreement was …

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Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl Jul 2009

Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl

Theses and Dissertations

Breast cancer is one of the most prevalent and deadly forms of cancer in women and is not restricted by race or ethnicity. Although a wealth of knowledge has been amassed on the biology of breast cancer, including its risk factors, diagnosis, prognosis, prevention, and treatment, it remains a serious health concern and active area of research. Initial response to standard chemotherapeutic and radiotherapeutic regimens is generally strong for many patients, yet breast tumors often recur, leading to more aggressive and resistant tumors. Because recurrence is such a clinical issue, more effective therapeutic approaches are needed to eliminate partial clinical …

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The Potential Role For Capb In Pathogenesis Of Francisella Tularensis, Eric Fleming Jul 2009

The Potential Role For Capb In Pathogenesis Of Francisella Tularensis, Eric Fleming

Theses and Dissertations

Francisella tularensis was a facultative intracellular pathogen and a gram-negative coccobacillus which has been categorized by the CDC as a potential class A select agent due to its highly infectious properties and high mortality rates. Francisella tularensis was also responsible for the zoonotic disease tularemia, which was usually transmitted by arthropod vectors or via contact with infected animals. Francisella tularensis subspecies novicida has been used by many researchers in genetic pathogenesis experiments to try to elucidate genes responsible for virulence factors. One of these virulence factors was a capsular material which has been thought to be involved in either increasing …

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Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner Jul 2009

Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner

Theses and Dissertations

Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth …

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Effect Of Posture On Acromiohumeral Distance With Arm Elevation In Subjects With And Without Rotator Cuff Disease Using Ultrasonography, Nitin Kalra Jul 2009

Effect Of Posture On Acromiohumeral Distance With Arm Elevation In Subjects With And Without Rotator Cuff Disease Using Ultrasonography, Nitin Kalra

Theses and Dissertations

Objectives: To examine the effects of posture on subacromial (SA) space with arm elevation in patients with rotator cuff disease (RCD) and healthy subjects. Background: Poor posture has been linked to altered scapular mechanics, theorized to lead to excessive SA space narrowing. However, no study has examined the direct effects of posture on SA space using ultrasonography. We hypothesize that when compared to a neutral posture, upright posture will increase SA space and slouched posture will decrease SA space. Methods: Subjects with painful RCD (n=31) and healthy (n=29) shoulders participated. SA space was measured on ultrasound generated images using the …

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Novel Allosteric Inhibitors Of Thrombin, Bijoy Desai Jul 2009

Novel Allosteric Inhibitors Of Thrombin, Bijoy Desai

Theses and Dissertations

Thrombin is a critical enzyme involved in blood coagulation and haemostasis. For this reason the study of its interactions with substrates, inhibitors and modulator is essential. It is also a unique enzyme in the serine protease family because unlike enzymes like trypsin and chymotrypsin its activity is modulated by various endogenous and exogenous ligands. This is due to the presence of “exosites” on the thrombin surface. Exosite II, unlike exosite-I, has not been characterized for its allosteric effect. In order to understand the structural basis of interaction and inhibition of inhibitor 4AS, which possibly interacts with exosite-II, native bovine thrombin …

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Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme Jul 2009

Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme

Theses and Dissertations

A majority of Americans regularly consume alcohol, but the risk factors leading to excessive drinking and alcohol abuse are unevenly distributed throughout the population. Genetic differences can account for only 40-60% of this variability. While variations in ethanol preference drinking in rodent models have been reported, the neurobiological factors underlying these behaviors are still not completely understood. Thus, these studies were designed to determine behavioral and molecular factors associated with the initiation of ethanol drinking preference in an inbred mouse model. We harnessed the power of inter-individual variation of ethanol drinking within an inbred mouse strain to essentially eliminate genetic …

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Chaperone Association With Telomere Binding Proteins, Amy Depcrynski Jul 2009

Chaperone Association With Telomere Binding Proteins, Amy Depcrynski

Theses and Dissertations

The Hsp90 chaperone complex associates with the telomerase enzyme, facilitating the assembly of the ribonucleoprotein complex. While previous data from our laboratory indicate that Hsp90 and p23 remain stably associated with (functionally active) telomerase, more recent experiments suggest that these chaperones associate with telomeres independent of telomerase, presumably through a specific interaction with telomere binding proteins. The current study examines the novel interactions between TRF2, TRF1, TIN2 and TPP1 and molecular chaperones (Hsp90, Hsp70, p23). In vitro and in cell experiments have shown an interaction between TRF1 and TRF2 and the molecular chaperones Hsp90 and Hsp70. Inhibition of Hsp90 using …

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