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Articles 31 - 60 of 132
Full-Text Articles in Medicine and Health Sciences
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 …
Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi
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 …
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 …
To Evaluate The Level Of Agreement Between Two Self-Reported Medication Adherence Scales And Prescription Refill Records In Older Adults, Priyanka Kakad
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 …
The Potential Role For Capb In Pathogenesis Of Francisella Tularensis, Eric Fleming
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 …
Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl
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 …
Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner
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 …
Novel Allosteric Inhibitors Of Thrombin, Bijoy Desai
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 …
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 …
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
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 …
Chaperone Association With Telomere Binding Proteins, Amy Depcrynski
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 …
Relationship Among Stress Of Labor, Support, And Childbirth Experience In Postpartum Mothers, Sasamon Srisuthisak
Relationship Among Stress Of Labor, Support, And Childbirth Experience In Postpartum Mothers, Sasamon Srisuthisak
Theses and Dissertations
Background: Due to the profound and life-changing aspects of giving birth and to each woman’s individualized birthing experience, it is important to understand the myriad of factors that contribute to a positive childbirth experience. The aims of this study were to: (1) identify factors related to a positive childbirth experience; (2) to examine relationships among women’s perceptions and personal evaluations of their childbirth experience, stress associated with labor pain, support from the nursing staff, initial contact with the baby following birth, support from partners, education, age, and obstetric history; and (3) to identify predictors of a positive childbirth experience. Method: …
Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura
Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura
Theses and Dissertations
Smith Magenis Syndrome (SMS) is a multiple congenital anomalies/ mental retardation disorder caused by deletion or mutation of the RAI1 gene on chromosome 17p11.2. The majority of patients with SMS phenotypes have a deletion or mutation of RAI1. However, some patients have been observed with SMS-like phenotypes and yet have no deletions or mutations in the RAI1 gene. One possible explanation could be aberrant methylation of RAI1 since RAI1 is present and yet may be silenced. In order to study this possibility, patient cell lines were treated with 5-Aza-2’-deoxycytidine. RNA was extracted and real-time PCR was used to check the …
Synthesis And Biochemical Studies On Sulfated Monomers Of Low Molecular Weight Lignins, Jenson Verghese
Synthesis And Biochemical Studies On Sulfated Monomers Of Low Molecular Weight Lignins, Jenson Verghese
Theses and Dissertations
Anticoagulants are used as the first line therapy for management and prevention of thrombotic disorders. Thrombin and factor Xa have been the prime targets for regulation of the coagulation cascade. In this work, a small library of 17 benzofuran derivatives were synthesized and screened against thrombin and factor Xa. The derivatives that displayed inhibitory potential were docked on the exosite-II of factor Xa using a docking protocol that was developed in our research group. These compounds were based on the β-5 structural unit found in the oligomer -'CDSO3‘, which was prepared in our lab and was found to inhibit both …
Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas
Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas
Theses and Dissertations
Smith-Magenis syndrome (SMS) is a complex mental retardation syndrome caused by deletion of 17p11.2 region or mutation of the RAI1 gene (retinoic acid induced 1). Individuals with SMS typically exhibit speech and motor delays, mental retardation, characteristic craniofacial and skeletal anomalies, and a distinct neurobehavioral phenotype that includes sleep disturbances, stereotypes, and maladaptive and self-injurious behaviors. RAI1 is thought to be a transcription factor modulating the expression of genes involved in a variety of cellular functions. Previous studies have shown the RAI1 gene being induced by retinoic acid (RA), a derivative of vitamin A. RA plays a significant role in …
Structural Interactions Between The Α3Β1 Integrin And Mmp-2: A Potential Functional Role In Cell Adhesion, James Bowman
Structural Interactions Between The Α3Β1 Integrin And Mmp-2: A Potential Functional Role In Cell Adhesion, James Bowman
Theses and Dissertations
During cardiac development and in cardiac disease changes in hemodynamic load initiate events leading to remodeling of the ECM. This study addresses the hypothesis that interactions between Integrins and Metalloprotienases function to modulate cell adhesion in the cultured cardiac fibroblast. The fibroblast is positioned to detect and respond to changes in the mechanical load on the heart. Functionally the cardiac fibroblast is the primary cell type responsible for the production, maintenance, and remodeling of the cardiac interstitium. Matrix Metalloproteinases, specifically the Gelatinases, are expressed in concert during development and in disease with changes in the hemodynamic loading of the heart. …
Development Of Hint Based Computational Tools For Drug Design: Applications In The Design And Development Of Novel Anti-Cancer Agents, Ashutosh Tripathi
Development Of Hint Based Computational Tools For Drug Design: Applications In The Design And Development Of Novel Anti-Cancer Agents, Ashutosh Tripathi
Theses and Dissertations
The overall aim of the research is to develop a computational platform based on HINT paradigm for manipulating, predicting and analyzing biomacromolecular-ligand structure. A second synergistic goal is to apply the above methodology to design novel and potent anti-cancer agents. The crucial role of the microtubule in cell division has identified tubulin as an interesting target for the development of therapeutics for cancer. Pyrrole-containing molecules derived from nature have proven to be particularly useful as lead compounds for drug development. We have designed and developed a series of substituted pyrroles that inhibit growth and promote death of breast tumor cells …
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Theses and Dissertations
ENZYMATIC REGULATION OF OPIOID ANTINOCICEPTION AND TOLERANCE By Lynn C. Hull, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Director: William L. Dewey, Ph.D. Department of Pharmacology and Toxicology The involvement of kinases in opioid actions has long been established. The acute actions of opioids, through the Gi/Go G-proteins, cause the inhibition of adenylyl cyclase and therefore a decrease in protein kinase A (PKA) activation. Additionally, acute opioid administration may cause the G-protein to activate the phospholipase C (PLC)-mediated cascade leading to the …
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Theses and Dissertations
Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic …
Th2 Specific Immunity And Function Of Peripheral T-Cells Is Regulated By The P56lck Sh3 Domain, Margaret Mccoy
Th2 Specific Immunity And Function Of Peripheral T-Cells Is Regulated By The P56lck Sh3 Domain, Margaret Mccoy
Theses and Dissertations
Proper T-cell activation and effector function are essential for effective immunity. T-cell antigen receptor (TCR) signals are known to regulate the outcome of differentiation, but the mechanisms remain unclear. Recent work from our lab demonstrates that the Src family protein tyrosine kinase, p56Lck, is able to specifically link TCR signals to activation of the Mitogen Activated Protein Kinase (MAPK) pathway through the function of its SH3 domain. The MAPK pathway is known to be involved in T-cell activation downstream of TCR ligation and has previously been implicated in T-helper type 2 (Th2) effector function. We have utilized an Lck SH3 …
Heritability Of Autoantibody Levels In A Twin Population, Amal Rastogi
Heritability Of Autoantibody Levels In A Twin Population, Amal Rastogi
Theses and Dissertations
AIM: This study aims to determine what portion of specific autoantibody phenotypes are genetically determined by using a twin model. METHODS: This study specifically examines Anti-Ro(SSA), Anti-La (SSB), Anti-Sn/RNP, Anti-Sm, Anti-Jo-1, Anti-Scl-70, Anti-Tg & Anti-TPO, Anti-dsDNA, Anti-PS, and Anti-cardiolipin antibodies for their heritability. This study examined 104 same-sex adult twins (66 monozygous, 38 dizygous) for the above mentioned autoantibody values. The serum autoantibody values in each subject were quantified using automated ELISA. Descriptive statistics including, distributions, quantiles, and moments were calculated by zygosity for continuous antibody values, subject ages, gender, race and smoking status. Categorical antibody levels were used to …
Identification Of Apoptosis Pathway In Treacher Collins Syndrome, Khaled Alsayegh
Identification Of Apoptosis Pathway In Treacher Collins Syndrome, Khaled Alsayegh
Theses and Dissertations
Treacher Collins Syndrome (TCS) is a rare autosomal dominant disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein called treacle. Model organisms have been generated to model the disease and have revealed knowledge about the etiology and pathogenesis of the disorder. The craniofacial abnormality observed in TCS patients is found to be caused by an increased level of apoptosis in the neuroepithelium and from this it has been suggested that treacle is important for proper formation and proliferation of neural crest cells that will ultimately contribute to the …
Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli
Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli
Theses and Dissertations
A targeted approach to the development of antifolate therapies has been sought for many years. Central to the success of such development is an understanding of the molecular mechanisms dictating the sensitivity of cells to antifolates and the fundamental differences of these processes between normal and neoplastic phenotypes. This dissertation addressed transcriptional mechanisms and cell-signaling events responsible for the efficacy of antifolate therapies. Transcriptional processes and cell signaling pathways are often aberrant in neoplastic tissues, providing a potential point of distinction between a normal and neoplastic cellular state. Folylpolyglutamate synthetase (FPGS) catalyzes the formation of poly-γ-glutamate derivatives of folates and …
Investigating The Response Of Oligodendrocyte Progenitor Cells To The Cuprizone Model Of Demyelination, David Moffatt
Investigating The Response Of Oligodendrocyte Progenitor Cells To The Cuprizone Model Of Demyelination, David Moffatt
Theses and Dissertations
Multiple sclerosis and other myelin diseases affect the quality of life many people. In the United States alone, multiple sclerosis afflicts as many as 400,000 individuals. Myelin, which is attacked by multiple sclerosis, plays a critical role in maintaining the healthy function of the adult nervous system. There are many model systems that study myelin and its formation and loss. Our lab investigates the cuprizone model of demyelination and remyelination. The cuprizone model is commonly believed only to affect adult oligodendrocytes, which it kills. The current study investigates whether other cells in the oligodendrocyte line, such as oligodendrocyte progenitor cells, …
Role Of Fdcs And Fdc Activation In Promoting Humoral Immunity Including Responses To T-Dependent Antigens In The Absence Of T Cells, Sayed Rania El
Role Of Fdcs And Fdc Activation In Promoting Humoral Immunity Including Responses To T-Dependent Antigens In The Absence Of T Cells, Sayed Rania El
Theses and Dissertations
Follicular dendritic cells (FDCs) reside in primary B-cell follicles and in the light zones of germinal centers (GCs) in secondary follicles, where their dendrites interdigitate forming extensive networks intimately interacting with B-cells. In GCs, FDCs can be found at the edges attached to the supporting reticular fibers. They trap and arrange immune complexes (ICs) in vivo and in vitro in a periodic manner with 200–500Å spacing and provide both antigen-specific and non-specific accessory signals to B-cells. FDCs exist in resting and activated states, with two characteristically different phenotypes. In their activated state, FDCs upregulate the expression of accessory molecules and …
Factors Influencing Placental Transfer Of Lopinavir: Binding, Uptake And Efflux, Abhishek Gulati
Factors Influencing Placental Transfer Of Lopinavir: Binding, Uptake And Efflux, Abhishek Gulati
Theses and Dissertations
HIV protease inhibitors are an important component of Highly Active Antiretroviral Therapy used to treat HIV infected pregnant women. They have a low placental transfer and are highly plasma protein bound. The purpose of this thesis was to characterize the factors limiting placental passage and fetal exposure to lopinavir. These factors include lopinavir plasma protein binding and uptake, cellular binding, and efflux of lopinavir in the placental trophoblast cells. First, we determined the unbound fraction of lopinavir in cord blood and characterized the binding of lopinavir to α1-acid glycoprotein (AAG) and human serum albumin (HSA), and displacement by ritonavir. Serum …
The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot
The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot
Theses and Dissertations
Chronic neuropathic pain is often difficult to treat due to its resistance to therapeutic intervention. This is due in part to the poor understanding of the physiological mechanisms involved in the establishment and maintenance of neuropathic pain states. The neuropathic pain model, chronic constriction injury of the sciatic nerve, produced robust pain hypersensitivity in our mice. It also induced significant changes in the mitogen activated protein kinase family, and the cannabinoid and µ-opioid systems in three different brain areas involved in the modulation or regulation of pain states. CCI induced a 2.5 fold increase in mRNA of the kinase Raf-1 …
Roles Of Krüppel Like Factors Klf1, Klf2, And Klf4 In Embryonic Beta-Globin Gene Expression, Yousef Alhashem
Roles Of Krüppel Like Factors Klf1, Klf2, And Klf4 In Embryonic Beta-Globin Gene Expression, Yousef Alhashem
Theses and Dissertations
Krüppel like factors (KLFs) are a family of 17 proteins whose main function is gene regulation by binding to DNA elements in the promoters of various genes. KLF transcription factors recognize CACCC-elements and act as activators or repressors of the gene expression. Among the 17 family members, KLF1, KLF2, and KLF4 share high homology to each other. KLF1 is the founding member of the family and is an erythroid-specific protein. KLF2 is expressed in erythroid, endothelial, and other cells. KLF4 is expressed in endothelial, smooth muscle, and other cells. In this thesis, the functions of these KLFs were reviewed in …
Prevalence Of White Spot Lesions During Orthodontic Treatment, Julian Dixon
Prevalence Of White Spot Lesions During Orthodontic Treatment, Julian Dixon
Theses and Dissertations
The reported prevalence of decalcification in orthodontic patients varies from 2 to 96% mainly due to the lack of a standard examination technique. The aims of this study were: 1) to determine the prevalence of white spot lesions around brackets using visual examination and the DIAGNOdent; 2) to determine which teeth were the most susceptible to decalcification; and 3) to test the accuracy of the DIAGNOdent by comparing to the visual examination. The presence of white spot lesions was determined in two groups of patients who were 6 and 12 months into orthodontic treatment, respectively. The control group consisted of …
The Effect Of Single Nucleotide Polymorphisms (Snps) In Toll-Like Receptors -2, -4, -9, And Cd14 Genes In An African-American Population With Chronic Periodontitis, Willard Maughan
Theses and Dissertations
AIM: to determine if a relationship exists between TLR-2, TLR-4, TLR-9, or CD14 polymorphisms and risk for developing chronic periodontal disease in an African-American population. This is the first study conducted to determine role of SNPs in TLR genes and CD14 gene in a periodontally-diseased African-American population. Additionally, this is the first study to assess the role of TLR-9 polymorphism in periodontitis patients. METHODS: A total of 130 subjects were involved in the study. The chronic periodontitis (CP) group contained 73 subjects, and the healthy control (NP) group 57subjects. Genotyping was performed in TLR2 (G2408A), TLR4 (A896G),TLR9 (T1486C) and CD14 …