Browsing by Subject "Life Sciences"

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17Beta-Estradiol Suppresses Hydrogen Peroxide-Induced Nuclear Factor Kappa B Activation in HT22 Cells
(2008-05-01) Kim, Pil J.; Simpkins; Singh; Yang, Shaohua
Kim, Pil J., 17beta-estradiol suppresses hydrogen peroxide-induced nuclear factor κappa B activation in HT22 cells. Master of Science (Biomedical Sciences), May, 2008, 78pp., 20 illustrations, 66 titles. Reactive oxygen species (ROS) are natural byproducts of normal cellular reactions. They are oxygen ions, free (non)radicals, and peroxides that are highly reactive with normal macromolecules, such as lipids, DNA, and proteins. Cells are normally able to defend against the damages of ROS via enzymes that neutralize them into water. However, when cells are not able to cope with the accumulation of ROS, distributions in signaling pathways and gene transcription will occur, which will ultimately lead to cell death. It is now widely accepted that increased oxidative stress-induced damage in the brain is a major cause of neurodegenerative diseases, such as Alzheimer’s disease (AD). Nuclear factor κappa-B (NFκB) is not only a ubiquitously expressed transcription factor but also a signaling protein that is activated by ROS-induced oxidative stress. Our laboratory has demonstrated the neuroprotective effects of 17β-estradiol (E2) are elicited via an anti-oxidant effect. The purpose of this project was to determine the role of NFκB activation in E2-mediated neuroprotection against hydrogen peroxide (H2O2)-induced oxidative stress. HT-22, a murine immortalized hippocampal neuronal cell line, was utilized to determine whether NFκB is activated by hydrogen peroxide-induced oxidative stress and whether E2 suppresses H2O2-induced NFκB activation. We observed that H2O2 activated NFκB by phosphorylation of IκBα (pIκBα), one of the NFκB inhibitor proteins, reduction of total IκBα, and induction of NFκB (p65) nuclear translocation. In contrast, E2 suppressed H2O2-induced NFκB activation by dramatic reducing pIκBα, increasing total IκBα, and inhibiting p65 nuclear translocation. Our results show that one of the mechanisms by which estrogens are neuroprotective against oxidative stress is through the attenuation of H2O2-induced NFκB activation.
[3H] Ethynylbicycloorthobenzoate ([3H] EBOB) Binding in Native and Recombinant GABAA Receptors
(2000-05-01) Yagle, Monica A.; Dillon, Glenn; Martin, Michael; de Fiebre, Christopher
Yagle, Monica A., [3H] Ethynylbicycloorthobenzoate ([3H] EBOB) Binding in Native and Recombinant GABAA Receptors. Master of Science (Pharmacology), May 2000, 59 pp., 3 tables, 7 illustrations, bibliography, 75 titles. Modulation of the GABAA receptor has been studied with noncompetitive convulsant ligands such as tert-butylbicyclophosphorothionate (TBPS) and picrotoxin (PTX). EBOB is a more recently developed ligand that appears to bind in the same region of the channel at TBPS, but with a higher affinity. While only a few studies have examined the binding of EBOB to vertebrate brain tissue and insect preparations, none have examined potential subunit-dependent binding of EBOB. We have thus examined [3H] EBOB binding in rat cerebellum and HEK293 cells stably expressing human α1β2γ2, human α2β2γ2, and rat α6β2γ2 GABAA receptors. For comparison, [35S] TBPS binding was also examined in α1β2γ2 receptors. Saturation and Scatchard analyses revealed saturable [3H] EBOB binding at one site in all tissue preparations with Kd values ranging from 3 to 9nM. [3H] EBOB binding, like [35S] TBPS binding was inhibited by the CNS convulsants dieldrin, lindane, tert-butylbicyclophosphorothionate (TBOB), PTX, TBPS, and pentylenetetrazole (PTZ) at one site in a concentration dependent fashion. Affinities were in the high nM to low μM range for all compounds except PTZ (low mM range). GABA modulated [3H] EBOB binding in a biphasic manner in α1β2γ2 receptors with a 100-fold difference between stimulatory and inhibitory affinities. Inhibition of GABA-mediated current by TBOB in α1β2γ2 receptors resulted in a functional IC50 of 0.2 μM, in agreement with binding study results. Differences seen in binding between the different receptor subtypes examined suggest that some characteristics of EBOB binding are subunit dependent. In addition, we have shown that [3H] EBOB is a useful ligand in the study of recombinant GABAA receptors and that results obtained with [3H] EBOB are comparable to those obtained with [35S] TBPS.
A Calcium-Dependent Nuclear Signaling Pathway Transcriptionally Silences Atrial Natriuretic Factor Gene Expression
(1995-08-01) Zeng, Hong; Stephen R. Grant; Walter McConathy; Richard Easom
Zeng, Hong, A Calcium-Dependent Nuclear Signaling Pathway Transcriptionally Silences Atrial Natriuretic Factor Gene Expression. Master of Science (Biomedical Science), August, 1995, 85 pp., 2 tables, 20 illustrations, bibliography, 90 titles. A cultured myocardial cell model was used to examine a potential role of calcium-dependent protein kinases and phosphatases in regulating the induction of the atrial natriuretic factor (ANF) gene mediated through adrenoreceptor signaling. In primary culture, rat neonate cardiomyocytes supplemented with phenylephrine (PE) following transfection (24 h) with a full length ANF promoter-reporter construct, showed elevated levels of promoter activity when compared to transfected cardiomyocytes cultured in the absence of PE. Prazosin, a dedicated α1-antagonist, completely blocked the transcriptional induction mediated through PE stimulation. Two different calcium mobilizing agents, BAY K8644 and gramicidin D, significantly reduced PE-stimulated ANF promoter activity. The over-expression of co-transfected exogenous CaM kinase II isoforms resulted in transcriptional silencing of PE-induced promoter activity for cardiac ANF. Transfection of a constitutively active, mutant form of the calcium-dependent phosphatase 2B, calcineurin, gene also transcriptionally silenced ANF gene expression. Exposure of PE-induced cardiomyocytes to either FK-506-treated cells in the absence of PE exposure suggesting that transcriptional silencing may be mediated through a transcriptional repression mechanism. Taken together, these results suggest that the activation of a Ca2+-dependent nuclear signaling pathway mediated through either CaM kinase II or calcineurin leads to complete transcriptional silencing of the embryonic ANF gene expression.
A Clinical Research Study Involving the Use of Erythropoietin in Perioperative Patients Undergoing Surgery for Gynecologic Cancer
(2002-07-01) Larson, Sharon Beth; Richardson, Barbara; Martin, Michael
The purpose of this internship practicum report is to analyze the pathophysiology and impact of anemia in low-income gynecologic cancer patients. The report also assesses the impact of erythropoietin on hemoglobin levels prior to gynecologic cancer surgery. This report is based on a clinical research study to determine whether or not erythropoietin will mitigate the suppression of bone marrow inherent to the gynecologic cancer population and alleviate some of the symptoms and side effects of the anemia.
A Critical Review of the One Hour and the Eight Hour Standards for Ozone with an Overview of the Proceedings that Led to the Implementation of The New Standard for Ozone
(2004-05-01) Palla, Amruth A.
Palla, Amruth R., A Critical Review of the One Hour and the Eight Hour Standards for Ozone with an Overview of the Proceedings that Led to the Implementation of The New Standard for Ozone; Master of Public Health (Environmental and Occupational Health), May 2004, 58 pp, 3 tables, 2 illustrations, 35 titles. With the increasing concern for human health and the recognition of the major role played by environment in the multi-factorial disease etiology, the various parameters established for maintaining the environmental constituents in the proportions desired for achieving a normal health status are taking an important position in the present day world. In 1997, during its review process the EPA found the exiting one-hour standards, for ozone to be insufficient to achieve the health friendly concentrations, and therefore proposed a new eight hour standard for this pollutant. The new standards proposed by the EPA were challenged by various other organizations and several proceedings have happened since then. The purpose of my thesis is to do a critical analysis of the advantages and the drawbacks of the two standards and to do an overview of the proceedings that have led to the implementation of the new standards.
A DNA-Based Multiplex Screening Tool for Separation of Fragmented and Commingled Skeletal Remains
(2007-12-01) Ambers, Angie; Joseph Warren; John Planz; Arthur Eisenberg
Ambers, Angie, A DNA-based Multiplex Screening Tool for Separation of Fragmented and Commingled Skeletal Remains. Master of Science (Forensic Genetics), December, 2007, 63 pages, 13 tables, 19 figures, references, 38 titles. In mass death scenarios, human remains are often fragmented, scattered, and commingled. Ascertaining the number of victims and determining the victims’ identities in such scenarios is a challenging task. A DNA-based screening tool used early in the investigation of mass disasters or mass graves would provide a relatively quick way to initially assess casualty numbers and separate remains for further analysis. Such a tool would promote the most efficient allocation of resources and speed the identification process. The multiplex designed here incorporates a few genetic loci that show high variability in the human population, giving it sufficient discriminatory power for separation of commingled remains. Specifically, the multiplex includes the amelogenin sex-determining locus, D3S1358, and a 3’ (CA)n dinucleotide repeat in the mitochondrial D-loop. Further optimization/validation studies need to be conducted, and a fourth locus (D5S818) may need to be considered to increase the tool’s power of discrimination.
A Meta-Analysis of the Effects of Chromium on Fasting Blood Glucose, HBA1c, Triglycerdies, LDL-C and HDL-C in Type 2 Diabetes and Impaired Glucose Tolerance
(2002-05-01) Evans, Jill E.; Urrutia-Rojas, Ximena; Mains, Doug A.
Evans, Jill E., A meta-analysis of the Effects of Chromium on Fasting Blood Glucose, HbA1c triglycerides, LDL-C, and HDL-C in Type 2 Diabetes and Impaired Glucose Tolerance. Master of Public Health, May, 2002, 35 pp., 4 tables, 4 figures, references cited, 23 titles. Objective: To assess the magnitude of chromium’s effect of trivalent chromium (picolinate or chloride) or yeast in type 2 diabetics or subjects with impaired glucose tolerance. Efforts were taken to combine studies with similar doses and treatment periods. Sensitivity analysis was performed. Outcomes Measured: Fasting blood glucose (FBG), HbA1c, triglycerides, high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C). Effect sizes were converted to appropriate units and were reported as “effect size equivalents”. Results: The magnitude of effect of chromium on FPG and HbA1c was negative and generally increased with dosage and duration. Statistically significant effects were observed for typical doses (150-250μg/day) for both outcomes at 1.5-3 months duration, and for HbA1c at 4-6 months; and high dosage (1000 μg/day) at 1.5-3 and 4-6 months for both outcomes. For triglycerides at the typical dose, statistically significant effects (p=0.00) were observed at 1.5-3 months. There was no effect on LDL-C. HDL-C increased with increasing duration of chromium supplementation, with the exception of the 4-6 month duration. Statistically significant effects (p=0.00) were observed for typical dosage at 1.5-3 months. For the studies using yeast with GTF activity, the effect size equivalent for FPG and triglycerides was significantly lowered (p [less than] 0.001 and p=0.00 respectively). When the study using yeast with no GTF activity was included, the pooled fixed effect size equivalent was smaller, yet remained significant. HDL-C was significantly increased (p=0.00). Sensitivity analysis yielded similar results. Conclusion: Meta-analysis of chromium showed a significant reduction in FBG, HbA1C, triglycerides, and LDL-C, while increasing HDL-C in the groups studied. The best available evidence suggests that chromium has a dose and duration-dependent effect on these outcomes.
A Mixed Methods Approach to the Definition of Family Health Promotion Practices for Mexican Sonoran Mothers
(2006-12-01) Montiel-Carbajal, Maria Martha; Lurie, Sue
Montiel-Carbajal, Maria M., A Mixed Methods Approach to the Definition of Family Health Promotion Practices for Mexican Sonoran Mothers. Doctor of Public Health (Social and Behavioral Sciences), December 2006, 143 pp., 14 tables, 1 illustration, bibliography, 55 titles. The purpose of this research was to study the family health promotion practices of a sample of Mexican mothers living in the state of Sonora Mexico through a concurrent mixed method approach that included (1) a qualitative component with face to face and in-depth interviews, investigator observations, and analysis of content; (2) a quantitative component consisting of statistical analysis of data from selected selections of the National Survey for the Evaluation of Health Services 2002-2003. For the qualitative component 15 mothers, with mean age of 40 years, mean years of education of 10 years, living with their families were selected to form a purposive sample, and assigned to one of three groups: married working mothers, non-married working mothers, or married non-working mothers. The qualitative component was naturalistic and descriptive using semi-structured interviews with the mothers, and individual questionnaires to collect demographic and housing information. The quantitative component used the survey responses provided by the database of the National Survey for the Evaluation of Health Services 2002-2003, from 404 female adults age 18 and older, living in the urban zone of Sonora. The qualitative component showed that mothers conceptualize the health status of the family as a priority. The specific practices they use depend on the set of external resources and internal strengths of the family in order to overcome the physical, environmental, relational, or economic barriers they found to the promotion of health practices. The participants also reported being unsatisfied with the access and quality of the social health care system. The data from the quantitative component showed that Mexican Sonoran women living in the urban area reported having good health and felt satisfied with their health status; their satisfaction with the social health care system was fair. The group of non-married working mothers was detected to be more at risk for cardiovascular diseases due to a greater proportion of smokers and drinking paired with low amount of exercise. The results provided valuable information to formulate health promotion programs and future policies to be implemented with the target population.
A Novel Approach to Inquiry-Based Learning Models in the Sciences: Utilization of Case Presentations and Patient Encounter Workshops in High School Life Science Classrooms
(2004-07-01) Whitaker, Lekeisha R.; Reeves, Rustin E.; Rudick, Victoria; Roque, Rouel
A Novel Approach to Inquiry-Based Learning Models in the Sciences: Utilization of Case Presentations and Patient Encounter Workshops in High School Life Science Classrooms. Lekeisha R. Whitaker. Abstract. A novel approach to inquiry-based learning models is needed in a curriculum that reflects changing demographics, societal demands, and diverse cultural background. The proposed module which is designed to teach the urinary system to Fort Worth Independent District high school biology students as outlined in the Texas Essential Knowledge and Skills (TEKS) guide, represents application of this novel tool in the classroom. It is designed to be implemented in inquiry-based learning classrooms that function to encourage the natural process of inquiry throughout grade levels. The proposed module takes advantage of media resources, introductory case reports, and patient encounter workshops that outline diet, disease, and health disparities as a way to capture student interest in content relevant material, engage students in the daily lessons, and invoke long-term retention of basic life science concepts. Through future research and testing of module design and effectiveness in the classroom, the proposed approach to inquiry-based learning may serve to optimize student understanding of fundamental science concepts and diet and disease as it relates to normal body function, with implications that may affect change in lifestyle. Furthermore, the proposed learning module, if effective, may also serve as a template to be used to teach other life science subjects.
A Novel sRNA Member of the Carbon Storage Regulatory System of Escherichia Coli
(2002-12-01) Weilbacher, Thomas; Jerry Simecka
Weilbacher, Thomas S., A Novel sRNA Member of the Carbon Storage Regulatory System of Escherichi coli. Master of Science (Microbiology & Immunology), December, 2002, 57 pp., 2 tables, 12 illustrations, bibliography, 44 titles. Small untranslated RNAs (sRNAs) perform a variety of important functions in bacterial systems. The 245 nt sRNA of Escherichia coli K-12, CsrC, was uncovered using a genetic screen for genes that regulate glycogen biosynthesis. CsrC RNA binds multiple copies of CsrA, a protein that post-transcriptionally regulates central carbon flux, biofilm formation, and motility in E. coli. CsrC antagonizes the regulatory effects of CsrA, presumably by sequestering this protein. The discovery of CsrC is intriguing, in that a similar sRNA, CsrB, performs essentially the same function. Both of these sRNAs possess similar imperfect repeat sequences (18 in CsrB, 9 in CsrC), primarily localized in the loops of predicted hairpins, which may serve as CsrA binding elements. Transcription of csrC increases as the culture approaches the stationary phase of growth and is activated by CsrA and the response regulator UvrY. Complementation and in vitro transcription-translation experiments reveal that CsrA effects on csrC are mediated indirectly, through UvrY. Because CsrB and CsrC antagonize the activity of CsrA and are dependent on CsrA for their synthesis, a csrB null mutation causes a modest compensatory increase in CsrC levels and vice versa. An updated model for the signaling circuitry of the Csr system is discussed.
A Phase II Clinical Study to Evaluate the Efficacy and Safety of rhThrombin in Subjects Undergoing Arterial Bypass Surgery and AV Graft Formation for Hemodialysis
(2004-12-01) Plascencia, Xochitl; Reeves, Rustin E.; Weis, Della; Peska, Don
The Association of American Medical Colleges Task Force on Clinical Research defines clinical research as a component of medical and health research intended to produce knowledge essential for understanding human disease, preventing and treating illness, and promoting health (Friedman, 1998). A clinical trial is defined as a research study conducted in humans which is designed to answer specific questions using scientifically controlled conditions with specified methodologies and endpoints (Gallin, 2002). Clinical research trials are essential in determining whether or not a drug is safe and effective. There are four phases that investigational drugs go through before they are allowed to be out in the market. Before beginning phase I of a study, there is usually a pre-clinical research and development phase. During this time the initial synthesis of study drug is accomplished and animal testing takes place. Phase I is the initial introduction of an investigational new study drug into humans. Phase I is usually conducted in healthy individuals and the primary goal is to determine the safety profile of the drug. Phase II trials tend to evaluate safety and initial efficacy. Subjects enrolled in this phase tend to have the disease necessary for use of study drug. Phase III studies are conducted to gather additional information about the effectiveness and safety of the drug and to determine the overall benefit-risk relationship of the drug. Finally, phase IV studies are usually referred to as post-marketing studies. During this phase, additional safety information is identified and the drug’s safety during routine use is evaluated. Each phase can range from two to ten years depending on the complexity of the clinical trial (Gallin, 2002). A phase II, randomized, double blind study of the safety and efficacy of topical recombinant human thrombin in patients undergoing peripheral arterial bypass surgery and arterio-venous graft formation for hemodialysis is the focus of the prospective drug study to be carried out in the surgery department at The University of North Texas Health Science Center. The primary objective of this study is to evaluate the safety and efficacy of recombinant human thrombin when used in different types of surgeries. Prior to signing an informed consent, subjects will have to meet inclusion and exclusion criteria set by study protocol. Study specific assessments and procedures will be performed after the informed consent is signed and dated. If bleeding at the anastomosis is found to necessitate intervention, a single application of either rhThrombin or placebo in combination with an absorbable hemostatic sponge to each anastomosis requiring hemostasis will be applied by the surgeon. The safety and efficacy of rhThrombin will be determined by measuring the incidence and severity of adverse events and of laboratory abnormalities. Occurrence of hemostasis within 600 seconds of application of the study drug at the anastomotic surgical site, incidence of anti-rhThrombin product antibodies, and time to hemostasis will also be measured.
A Review of Dendritic Cell Vaccines in Cancer Treatment and a Managerial Focus on Issues Related to Subject Recruitment
(2006-12-01) McFarlin, Tory; Arredondo, LaChelle; Gwirtz, Patricia A.; Oglesby, Michael
McFarlin, Tory. A Review of Dendritic Cell Vaccines in Cancer Treatment and a Managerial Focus on Issues Related to Subject Recruitment. Master of Science (Clinical Research Management), December 2006, 97 pp., 5 tables, bibliography, 24 titles. Melanoma is form of skin cancer that can become deadly if the cancer progresses to a stage of metastasis. Five year survival rates as low as 10% may be noted in such patients. Decarbazine and Proleukin have been approved by the FDA for the treatment of metastatic melanoma; however both have response rates of approximately 20% or less. New treatment modalities including dendritic cell (DC) vaccines are currently being tested for treating metastatic melanoma with greater safety and efficacy profiles. DC vaccines are made by obtaining a subject’s DCs, priming them with melanoma antigen ex vivo and then injecting them into the patient to initiate an immune response against melanoma tumor cells in vivo. Investigational new treatments such has the DC vaccine must first be tested in clinical trials on research subjects. Subject enrollment issues regarding such a trial can cause delays in advances of the treatment. As an intern with a DC vaccine clinical trial, the author assisted in screening 45 patients and observed many hindrances involving enrollment of subjects. Such hindrances include: low rates of study personnel retention, small patient pools, and competing trials. Recommendations to improve enrollment include: more effective advertisement strategies and increased patient education.
A Study of Disparities in the Receipt of Anti-Retroviral Drugs, Health Status, and Insurance Coverage Among a Sample of HIV-Positive Adults
(2006-12-01) Wittenmyer, Brian F.; Lykens, Kristine; Talbert, Jeffrey; Strawderman, Tim
Wittenmyer, Brian F., A Study of Disparities in the Receipt of Anti-Retroviral Drugs, Health Status, and Insurance Coverage among a Sample of HIV-Positive Adults. Master of Public Health (Health Management and Policy), December 2006, 88 pp., 8 tables, references, 32 titles. Anti-retroviral medications (ARV) are effective at treating HIV/AIDS. Medicare, Medicaid, and ADAP are public programs that supply ARVs to needy patients in the U.S. Studies have documented dispartities in AIDS incidence/prevalence, insurance, and ARV-use. The study described demographic, clinical, and insurance characteristics of a sample of HIV+ persons. The study explored relationships between AIDS diagnosis, health status, and ARV-receipt and demographic, insurance, and clinical variables. Disparities in ARV-receipt, AIDS diagnosis, and health-status were found for gender, age, race, geographic region, and SES. Policy recommendations included: shortening the disability waiting-period for Medicare-eligibility, and relaxing Medicaid’s income-eligibility requirements.
A Study of Pesticide Safety and Health Perceptions Among Tarrant County Pesticide Applicators
(2001-05-01) Martinez, Robert A.; Gratton, Terrance B.; Coggin, Claudia S.; Atkinson, Sam
Pesticides have become an important part of our lives. We rely on them to help protect our crops from pest; they rid our homes of unwanted pests and help us make our lawns and public parks beautiful. Pesticides are also important to public health. They are a major source of vector control and help stop the spread of vector-borne disease. Even though we used them in our everyday lives, it is important to remember that pesticides are poisons, and that great care must be taken to ensure the safety of the public and safety of those who work with pesticides. This study looked at the safety knowledge and health perceptions among Tarrant County, Texas licensed applicators. Much research has been focused on the effects of pesticides on human health. Much of this research has been focus on the farmer applicator (Alavanja, 1999). This study focuses on applicators that work mostly in the urban areas of the County, as well as ranchers live in the County. These licensed urban applicators included those who work for city parks departments, golf courses, commercial applicators, lawn care service, pest control and some private ranchers. The Texas Pesticide Regulations require that a person may not use a restricted-use or state-limited use pesticides or herbicides unless licensed by the Texas Department of Agriculture (2000). Therefore the purpose of this study is to see if an association between health beliefs and pesticide safety knowledge exist. The reason it is important is because these people can have either a positive or negative impact on the safety of themselves and their crews. Acute pesticide poisoning is one of the biggest risks that applicators face. The state of Texas conducts an active surveillance of occupational-related pesticide poisonings. The Environmental Epidemiology and Toxicology Division at the Texas Department of Health (TDH) have had this system in place since 1985. TDH reported that 107 work related cases occurred during 1998, with 55 confirmed as occupational pesticide poisoning (1998). The most frequent symptoms reported were neuromuscular symptoms such as headaches, dizziness, confusion, irritability, and twitching muscles. Pyrethroids and pyrethins were the most commonly reported class of pesticides exposure (51%) followed by Organophosphates (25%), which are the most widely used form of insecticides, as well as herbicides and fungicides. Pesticide safety and the TDH surveillance system are two very important ways of informing pesticide applicators about the risk and what can be done to minimize that risk to themselves and their crew.
A Study of Some Aspects of the Role of Mast Cells in Experimental Autoimmune Uveitis
(1994-06-01) Lee, Carol Hamberlin; Orr, Edward; Gracy, Robert; Lang, Laura S.
Lee, Carol Hamberlin, A Study of Some Aspects of the Role of Mast Cells in Experimental Autoimmune Uveitis. Doctor of Philosophy (Biomedical Sciences), June 1994, 141 pp., 6 tables, 29 illustrations, bibliography, 115 titles. Choroidal mast cells have been implicated in experimental autoimmune uveitis (EAU), an ocular inflammatory disease induced by S-antigen (Sag). Activation of ocular mast cells in Lewis rats was evaluated by determining changes in numbers of mast cells, levels of histamine, and wet weights of ocular tissues. A decrease in choroidal mast cells was confirmed statistically, and limbal mast cells were found to be activated earlier than choroidal mast cells. The ocular histamine distribution was altered during EAU, decreasing in the anterior eye, and increasing in the posterior eye. Retinal histamine levels increased when EAU symptoms occurred, but decreased while the disease was still intense. Levels of histamine methyltransferase, which degrades histamine, increased significiantly in retinal tissue when histamine levels fell. Signficant weight increases indicated edema, which can result from mast cell mediator action. Leflunomide, an immunomodulating drug that is known to affect mast cells in vitro, prevented induction of EAU. Leflunomide also suppressed changes in the mast cell-related parameters, histamine levels and wet weights. Mechanisms for activation of ocular mast cells in EAU were investigated. Results suggest that mast cell activation does not occur through mast cell surface IgE-antigen crosslinking. The adjuvant used, complete Freund’s adjuvant, is not conducive to IgE production. Histamine releasing factors, HRFs, are produced by various immune system cellular components. Preliminary efforts did not demonstrate HRF activity. Mast cell numbers, histamine levels, and wet weights were also evaluated in a milder form of EAU induced by M-peptide (Mpep), a peptide fragment of Sag. Mpep/EAU produces few disease symptoms in the anterior eye, but destroys the same retinal area as Sag/EAU—photoreceptor cells and their outer segments. Inflammation is less intense, restricted primarily to the target area. Mast cell numbers did not change, but histamine levels and wet weights changed significantly, suggesting that mast cells are also involved in Mpep/EAU. Overall, the results of this study add to evidence that mast cells are involved in pathogenesis of EAU. The results also point to topics of further investigation into the role of mast cells in EAU and in normal function in ocular tissues.
A Study of the Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for Three Months Versus Daily Isoniazid for Nine Months for the Treatment of Latent Tuberculosis Infection
(2004-11-01) Lemp, Jessie; Patricia Gwirtz; Walter McConathy; Richard Easom
Lemp, Jessie M. A Study of the Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for Three Months Versus Daily Isoniazid for Nine Months for the Treatment of Latent Tuberculosis Infection. Master of Science, November, 2004, 107 pp., 4 tables, 4 figures, references, 29 titles. The standard treatment for latent tuberculosis infection, nine months of daily isoniazid, is effective at preventing active tuberculosis; however, its full benefits are limited by non-adherence. A shorter intermittent regimen of rifapentine plus isoniazid once weekly for three months is equally effective as the standard regimen in animal models. This regimen facilitates the use of directly observed therapy, a method that significantly improves adherence. The Center for Disease Control is sponsoring Study 26 to test the effectiveness and tolerability the three-month rifapentine based regimen in latently infected persons with risk factors for progression to active tuberculosis. This thesis will describe the background rationale and methods for the clinical trial, and the internship experience.
A Study of the Efficiency of the Combined DNA Index System for the Oregon State Police
(2007-08-01) Brown, Allison A.; Joseph Warren; Arthur Eisenberg; John Planz
Method of Procedure: This project, which was conducted at the Oregon State Police Crime Laboratory, entailed following up with CODIS hits. It involved examining cases that have been worked by forensic scientists and finding explanations as to how the cases are proceeding after NDA matches are made. Failures to follow up on a CODIS hit have become a national problem in forensic laboratories all over the country. The Oregon State Police find this a very important issue that must be resolved. Currently the Oregon State Police are getting a hit, an arrest and a conviction. The only problem with all of this is that it is hard to measure the efficiency of CODIS hits with just convictions. There are several ways the cases could have been resolved such as the victim did not want to pursue the case any further, the suspect was already incarcerated for another crime, the witnesses were hard to locate or the case was dropped because of a plea to other crimes. As part of my research I investigated each of the cases that have been worked to see if they were pursued any further after a hit to an individual. After researching these cases, it was my responsibility to put my findings into a format that made it easier for the state police to know how the cases were resolved. The information was collected using a variety of software programs. The reason that more then one computer program needed to be used in the project, is due to the fact that more of then not some of the information that should have been provided in a program was absent in one and present in another program. The California Department of Justice currently has a system that is available which allows its users to input data. In order to design such a system it was my responsibility to obtain the case information. Once this had been obtained it made it easier to combine the data into a table format so that the state police could see how each case was proceeding. Below is a table of exactly what information was obtained. Due to the confidentiality of the information, false names and false information will be used in all tables seen. Once the information for one thousand hits had been gathered it was placed into Microsoft Access so that a database could be created. Throughout the time that CODIS has been in place, crimes where DNA matches have been made but not pursued have shed light upon a common problem occurring everywhere in forensic laboratories. Dozens of cases have found matches between a suspect and a crime but there has been no pressure to pursue the case any further. In fact one unfortunate result has been multiple DNA matches of a suspect, with the suspect continuously making repeated offenses. Most of the offenses are nor pursued until the investigators realize there might be a link between the current crime and the past cases worked. Only then are the reports of the DNA matches reviewed and pursued further. In one Virginia case, this scenario occurred. A man by the name of William Orlando Smith followed a girl and raped her in the woods. Had the DNA match that the Virginia police made months earlier been pursued, the rape might have been prevented. This is not just one isolated event but a common occurrence seen in other states as well. Although this research for the Oregon State Police might not resolve a national issue, it will aid in preventing scenarios like the above from possibly occurring. By solving this problem and entering how cases are resolved into a database like Microsoft Access, it will make it easier for the investigators to process crimes. Even more important is the need for this information to be compared with other states. A study such as this will enable states to test the efficiency of CODIS.
A Study to Determine Improved Compliance of Biophosphonate Treatment in Subjects with Osteoporosis
(2005-02-01) Enard, April T.; Gwirtz, Patricia A.; Jimenez-Williams, Cynthia; Rubin, Bernard
Enard, April T. A Study to Determine Improved Compliance of Bisphosphonate Treatment in Subjects with Osteoporosis. Master of Science, February 11, 2005. The ability of patients to adhere to treatment regimens is very poor and continues to impede optimal therapy of osteoporosis. The shortcomings in treating osteoporosis are: a) noncompliance and/or lack of continued persistence of therapy, b) efficacy of therapy on bone turnover marker levels and fracture prevalence, and c) tolerability of therapy to patients. Studies have shown that interventions such as education and awareness of bone mineral density promote patient usage compliance. The slightest improvement in compliance allows further understanding of accurate efficacy of medication therapy to fractures, bone marker levels, and overall improvement of bone mass. Increased compliance/persistence allows accurate comparison of bisphosphonates to one another for effectiveness on osteoporosis patients and allows improvement opportunity in treatment modalities that can positively influence the course of osteoporosis. This phase IV study targets compliancy/persistence in bisphosphonate therapy in treatment of osteoporosis.
A Systematic Screen of the Saccharomyces Cerevisiae Deletion Mutant Collection for Novel Genes Required for DNA Damage-Induced Mutagenesis
(2008-07-01) Gong, Jinjun; Siede, Wolfram; Sheedlo, Harold; Reeves, Rustin
A Systematic Screen of the Saccharomyces Cerevisiae Deletion Mutant Collection for Novel Genes required for DNA Damage-Induced Mutagenesis. Jinjun Gong Department of Cell Biology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107. Summary. Deoxyribonucleic acid (DNA) damage is common in a cell’s lifetime. DNA can be damaged by endogenous factors such as reactive oxygen species (ROS) or exogenous agents such as ultraviolet (UV) or industrial chemicals. DNA damage will trigger cell responses including cell cycle arrest, transcription activation, DNA repair or apoptosis. In addition to various DNA repair mechanisms including damage reversal, base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end joining, translesion DNA synthesis is an important DNA damage tolerance pathway that can bypass the lesion on template DNA to finish the replication for cell survival but at the risk of potential mutation in the daughter cells. Accumulation of mutation may lead to cancer occurrence. Translesion DNA synthesis components are highly conserved from yeast to humans. Important players in trans-lesion synthesis pathway such as Rev1, Rev3 and Rev7 were first discovered in budding yeast. Saccharomyces cerevisiae. Homologues were found later in human cells. I used the Saccharomyces cerevisiae deletion mutant collection to do a systematic screen to search for novel genes required for DNA damage induced mutagenesis in yeast. After CAN1 forward mutation assay for the systematic screen and reverse mutation assay for further confirmation, two candidate genes SWI6 and DOA4 were detected. Deletion of SWI6 and DOA4 decreases mutagenesis of cells. At the molecular level, Swi6, a transcription cofactor, is involved in mutagenesis by regulating expression of REV7 at the mRNA and protein levels. Rev7 is a regulatory subunit of DNA polymerase zeta, which is essential for DNA damage induced mutagenesis as well as spontaneous mutagenesis. Rev7 is not UV inducible or cell cycle regulated. The regulation of Rev7 at the transcriptional level by Swi6 is essential. Future experimental approaches are planned to address the mechanism by which DOA4 is involved in mutagenesis.
Acetoacetate: A Cardioprotective Antioxidant
(2002-05-01) Squires, Jeffrey E.; Mallet, Robert T.; Caffrey, James L.; Carroll, Joan
Squires, Jeffrey E., Acetoacetate: A Cardioprotective Antioxidant. Master of Science, June 2002, 100 pp., 1 table, 18 illustrations, bibliography, 70 titles. The purpose of this study was to test the effectiveness of acetoacetate and β-hydroxybutyrate as myocardial protectants following peroxide injury and to determine acetoacetate’s ability to potentiate β-adrenergic responsiveness following ischemia-reperfusion injury. This study utilized antegradely perfused isolated working hearts exercised from male guinea pigs and sustained with glucose-fortified Krebs-Henseleit. Hearts were challenged by either 10 min perfusion with 100 μM H2O2 or 45 min of low flow ischemia exacerbated by ι-norepinephrine infusion. H2O2-challenged hearts were treated with 5 mM acetoacetate or β-hydroxybutyrate, whereas hearts injured by ischemia/reperfusion were treated with 5 mM acetoacetate. In the case of the ischemically injured hearts, acetoacetate treatment was combined with 2 nM isoproterenol to delineate acetoacetate’s ability to enhance β-andrenergic responsiveness to submaximal inotropic stimulation. Data were compared to non-injured time control hearts and injured untreated hearts to determine the impact of ketone body treatment. Acetoacetate increased citrate and glucose 6-phosphate content, nearly restored power, and increased the glutathione antioxidant redox potential (GSH/GSSG) by 140% in H2O2-injured myocardium. Although β-hydroxybutyrate increased citrate, an activator of NADPH-generating pathways, and glucose 6-phosphate, the substrate for the hexose monophosphate shunt to the same extent as acetoacetate, β-hydroxybutyrate raised GSH/GSSG by only 60% and did not enhance cardiac power. Therefore, acetoacetate enhances contractile function by augmenting the glutathione redox potential, and does so by additional mechanisms independent of the citrate and hexose monophosphate pathway. In hearts stunned by ischemia/reperfusion, acetoacetate and isoproterenol each increased power and glutathione redox potential three-to-fourfold, but phosphocreatine potential was 70% higher in acetoacetate hearts. Combined, acetoacetate + isoproterenol synergistically increased power and GSH/GSSG 16- and 17- fold respectively, doubled {NADPH/NADP+}, and increased cyclic AMP content 30%. These findings support the conclusion that acetoacetate enhances myocardial sensitivity to β-adrenergic stimulation possibly by enhancing GSH/GSSG.