Browsing by Subject "Medical Sciences"
Now showing 1 - 20 of 265
- Results Per Page
- Sort Options
Item 17 Beta-Estradiol, Integrins, and Synaptic Proteins(2009-05-01) Chandra, Manjari; Simpkins, James W.Item 2007 Annual Report(2007-01-01)Item 2011 Bibliography of Publications(2012-06-13) Mason, Tim; Lindsey, MarylouiseItem [3H] Ethynylbicycloorthobenzoate ([3H] EBOB) Binding in Native and Recombinant GABAA Receptors(2000-05-01) Yagle, Monica A.; Dillon, Glenn; Martin, Michael; de Fiebre, ChristopherYagle, 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.Item 5 Year Strategy: 2009-2014(2008-01-01)Item A Cadaveric Investigation of the Dorsal Scapular Nerve(2016-12-01) Nguyen, Vuvi H.; Reeves, Rustin E.; Liu, Hao; Rosales, Armando A.Dorsal scapular nerve (DSN) syndrome is often associated with sharp, dull, or aching pain in the upper extremity and back. The primary cause of pain is the entrapment of this nerve at the middle scalene muscle. Even though there is clinical evidence that DSN syndrome exists, it is often overlooked during clinical diagnosis. The purpose of this study is to locate the surface projection of the DSN relative to the middle scalene muscle while using the laryngeal prominence as a reference point. From 20 embalmed adult cadavers, 23 DSN were dissected and documented regarding its spinal root origins, anatomical route, and muscular innervations. A transverse plane through the laryngeal prominence was established to measure the distance of the DSN as it enters, crosses, and exits the middle scalene muscle. Approximately 70% of the DSNs originated from C5, 22% branched from C4, and 8% from C6. In regards to the route of the DSN in relation to the middle scalene muscle, 74% of the DSNs pierced this muscle, 13% crossed this muscle anteriorly, and 13% traveled posterior to this muscle. About 48% of the DSNs supplied the levator scapulae muscle only and 52% innervated the levator scapulae and both the rhomboid muscles. The average distances from a transverse plane of the laryngeal prominence to where the DSN entered, crossed, and exited the middle scalene muscle were 1.50 cm (±0.88 cm), 1.79cm (±0.89 cm), and 2.08 cm (±0.96 cm) respectively. Injection studies were performed on 10 un-dissected embalmed cadavers to verify the accuracy of our surface projection measurements of the DSN relative to the middle scalene muscle. These injections were performed at approximately 2.08 cm (~1 thumb interphalangeal joint width) from the transverse plane of the laryngeal prominence. Dissections at these injection sites revealed that the scalene muscles were consistently located. The middle scalene muscle was accurately located in approximately 50% of the injections. The goal of this research is to understand the variability in DSN's anatomy as well as introduce a method that will assist clinicians to efficiently pinpoint and therefore treat patients with DSN entrapment.Item A Calcium-Dependent Nuclear Signaling Pathway Transcriptionally Silences Atrial Natriuretic Factor Gene Expression(1995-08-01) Zeng, Hong; Stephen R. Grant; Walter McConathy; Richard EasomZeng, 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.Item A Comparative Review of Screening, Consent, and Trial Visits and Follow-up Practices in Cardiovascular Dual Antiplatelet Therapy Drug, Device, and Registry Studies at Legacy Heart Center and The Heart Hospital Baylor Plano(2014-12-01) Mohiuddin, Ismail S.; Patricia A. Gwirtz; Rustin E. ReevesCoronary artery disease (CAD) is the number one cause of death in the United States and a large amount of research has been conducted to find the best treatment strategy to treat and prevent it. The PEGASUS-TIMI 54 study, a drug trial, the PzF SHIELD study, a device trial, and the TIGRIS study, a registry trial, build off of that research and are seeking novel strategies to improve patient outcomes There are significant differences between drug, device, and registry clinical research trials. Comparing these three dual antiplatelet research studies on the basis of screening, consent, and trial visits and follow-up practices gives insight into the distinct features of each kind of clinical research trial.Item A Cross-Sectional Study on Factors Affecting Maternal Trust in Texas Government to Make Good Decisions About Newborn Screening and Dried Bloodspot Storage(2015-12-01) Nguyen, Huy David Dang; Robert T. Mallet; Peter B. RavenNewborn screening (NBS) results in a surplus of blood samples in the form of dried bloodspots (DBS). Texas’s “opt-in” policy requires mothers’ permission for the state to store DBS samples for research. A cross-sectional study was performed on post-partum mothers in North Texas to determine the effect of the mothers’ demographics, knowledge, attitudes, and decisions about NBS and DBS storage on trust in Texas’ ability to make good decisions regarding bloodspot research. The aforementioned trust in the Texas government was strongly associated with trust in Texas to keep the babies’ information private, belief that using DBS for public health was beneficial, and trust in Texas to de-identify their babies’ DBS. Medicaid coverage also showed a slight association with this trust. Overall, mothers who are supportive of public health research using de-identified specimens such as DBS are more confident in the Texas’s ability to make the right choices regarding DBS storage.Item A guanidine dietary supplement influences pH sensitivity and NSAID activity in acid-sensing ion channels(2015-12-01) Agharkar, Amruta S.; Gonzales, Eric B.; Singh, Meharvan; Luedtke, Robert R.The acid-sensing ion channels (ASICs) are proton sensitive, sodium channels that belong to the epithelial sodium channel/ Degenerin family of ligand-gated ion channels. Activation of the ASIC1a subtype in the central nervous system increases neurodegeneration after ischemic stroke while ASIC3 subtype in the peripheral nervous system is involved in perception of pain. They are emerging targets for ischemic stroke, pain and inflammation. However, we lack selective ligands to target ASICs. In order to gain a better understanding of the channel and to develop selective ligands we must first determine how ASICs are modulated by synthetic as well as endogenous guanidine compounds. This study investigates whether a guanidine dietary supplement, creatine, modulates ASICs. Creatine has been shown to protect from ischemia and benefits patients suffering from muscular dystrophy, osteoarthritis, and fibromyalgia. Furthermore, pain medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit ASICs. Since supplements and NSAIDs are available over-the-counter, the significant amount of the population would consume them simultaneously.However, the interactions of combination of creatine and NSAIDs on ASICs still remain elusive. Here we sought to determine if creatine would modulate ASIC1a and ASIC3 proton sensitivity and if the combination of creatine and NSAIDs would inhibit ASIC3. Our results indicate that, creatine reduces human ASIC1a (hASIC1a) steady-state desensitization and increases their recovery from desensitization. Creatine also slows down the open-state desensitization of hASIC1a. The efficacy of hASIC1a is increased by creatine at higher concentrations. This indicates that, creatine increases channel's reactivation from desensitization by stabilizing the closed conformation of hASIC1a. Creatine's effect on rat ASIC3 (rASIC3) was calcium dependent. Creatine reduced proton sensitivity of rASIC3 in the nominal calcium environment. As previously reported, NSAIDs inhibited steady-state current of rASIC3 which is involved in pain perception. However, creatine reduced NSAIDs efficacy on rASIC3. To summarize, the creatine's effect depends on the desensitized state of hASIC1a and creatine increases the availability of channels for opening. While in rASIC3, creatine reduces proton sensitivity in nominal Ca2+ and antagonizes NSAIDs inhibitory effect. Thus, the use of creatine should be monitored in diseased states and when it is consumed along with NSAIDs.Item A Novel Multiplex Assay for an Ancestry-Informative Marker (AIM) Panel of INDELs(2016-05-01) Sturm, Sarah A.; Bobby L. LaRue; Bruce Budowle; Raghu R. KrishnamoorthyThe current standard for forensic laboratories in criminal casework is to use Short Tandem Repeat (STR) markers to develop an evidentiary profile. Commercially available STR amplification kits yield amplicons 100 to 500 base pairs (bp) in length. Commonly, forensic DNA samples are highly degraded to approximately 180-200 bps in length, resulting in incomplete STR profiles. Therefore, markers that can be generated with smaller amplicons may be better suited for degraded DNA samples. Additionally, there are cases where no STR match was obtained through a DNA database search and thus no investigative lead is obtained. The bioancestry of a sample donor could aid law enforcement in such cases. A class of markers that could provide investigative value from degraded DNA samples is Ancestry-Informative Marker (AIM) Insertion/Deletions (INDELs). INDELs are polymorphisms that can be amplified from degraded samples due to their smaller amplicon size. AIMs have the ability provide bioancestry information. This project tested the hypothesis that a multiplex PCR-based assay of INDELs can be developed, and subsequently be analyzed by capillary electrophoresis for population identity testing applications. The use of this assay would require no additional tools or machinery than what already is in standard forensic laboratories. To test this hypothesis, a previously developed panel of AIM-INDEL markers was used to develop this multiplex assay.Item A Pilot Study into the Impact of Remote Monitoring on the Trial Site(2017-12-01) Paulman, Brendan; Stephen O. Mathew; Scott MadduxRemote monitoring as the primary method of clinical trial oversight is increasingly common due to advancements in technology which allow SDV to be performed without site visits. However, remote monitoring often changes the workflow of the clinical trial site staff. This study aims to determine how remote monitoring affects the time allocation of site staff toward duties related to monitoring visits, and to identify which tasks are most affected when the sponsor uses a remote monitoring strategy. A survey was sent out to clinical research staff within BSWRI. Research staff tended to spend less time toward remote monitoring duties than on-site monitoring duties. Submitting source documents, regulatory, and AE documentation were identified as more time-consuming for remote monitoring, while preparing for visits and assisting the monitor while on-site were identified as more time-consuming for on-site monitoring. This study identified potential targets for improvements in the workflow of clinical trial sites.Item A Pragmatic Work Flow for Manual Medical Chart Review: A Systematic Literature Review(2014-12-01) Qiu, Taoran; Patricia A. Gwirtz; Kunlin JinThere has been a lack of detailed description of the manual medical chart review process with standardized steps for data abstraction. The aim of this practicum thesis is to develop a pragmatic and systematic work flow for the manual reviewing of medical records. The thesis is conducted by systematically reviewing publications from the last twenty years. The end product of this practicum report is series of twelve steps work flow for manual medical data abstraction.Item A Retrospective Study on Delayed Graft Function after Deceased-Donor Kidney Transplantation(2017-12-01) Keeton, Kamaryn; Robert T. Mallet; Harlan P. Jones; Stephen O. MathewDelayed graft function (DGF) following renal transplantation may be more severe in kidneys from deceased vs. living donors due to ischemia-reperfusion. Data was analyzed from 40 living and 49 deceased donor-recipient pairs from January 2012-13 at two centers. DGF incidence was greater in kidneys from deceased (52.1%) vs. living donors (12.1%). Comparison of DGF incidence in deceased vs. living donor kidneys yielded χ2 = 14.225 and p = 0.0002. Regression analyses of post- vs. pre-graft changes in serum creatinine vs. cold ischemic time, donor body mass index, donor age and terminal serum creatinine were not significant. These results indicate delayed functional recovery of transplanted kidneys from deceased vs. living donors, which is important when determining a plan of care for these patients.Item A Semi-Automated Methodology for Extraction of DNA from Human Skeletal Remains(2013-05-01) Mize, Mary L.; Arthur EisenbergThe current methodology used by the University of North Texas Center for Human Identification Missing Persons Laboratory (UNTCHI) to recover DNA from skeletal remains is time-consuming, laborious and not readily amenable to automation. The constraints of the current process limit the number of samples that can be analyzed. The results of this study show that extractions performed with the AutoMate Express™ Forensic DNA Extraction System (Life Technologies, Carlsbad, CA) can produce comparable DNA quantity and quality to the current procedure used by UNTCHI. The utilization of the AutoMate Express™ Forensic DNA Extraction System in our operational laboratories would help streamline the process of DNA extraction from human skeletal remains and potentially provide increased amounts of genetic information.Item A Survey of Anticoagulation Non-Adherence in Emergency Department Patients Presenting with Atrial Fibrillation(2017-12-01) Harla, Sean; Patricia A. Gwirtz; Amalendu P. RanjanIntroduction: Patients with atrial fibrillation are at an increased risk of stroke. As part of stroke prevention, these patients are prescribed anticoagulants. The Emergency Medicine Department at the University of Texas Southwestern undertook a survey study to ascertain why some Emergency Department (ED) patients with atrial fibrillation are compliant with taking their anticoagulant therapy, whereas others are not. The objective was to assess whether or not patient health literacy/ numeracy played a significant impact on patient anticoagulant non-adherence. Methods: The Newest Vital Sign (NVS) survey and Modified Morisky Scale (MMS) survey were administered to the subjects to measure their health literacy/ numeracy as well as level of motivation/ knowledge, respectively. Results: Results showed that patient knowledge and motivation may have surpassed patient health literacy/ numeracy in impacting anticoagulant compliance among ED patients with a history of atrial fibrillation. Patient enrollment however did not meet threshold for power. As such, the results did not show statistical significance. Conclusion: It is therefore recommended that future research continue in order to attain a large enough sample size to render statistically significant findings.Item 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, RustinA 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.Item A Validation of STRmix™ for Forensic Casework(2017-05-01) Conway, Allison; Bruce Budowle; Joseph E. Warren; Patricia A. GwirtzThe interpretation of complex DNA profiles has been a controversial issue in forensic biology. The current methods of interpretation are limited in scope and do not make full use of the data. Efforts have been made to develop software which can incorporate more data and process more calculations than were previously possible. One such program, STRmix™ (Institute of Environmental Science and Research, Porirua, New Zealand), uses a Markov Chain Monte Carlo (MCMC) principle to simulate many different possible profiles and determine the probability of observing a profile in the evidence. A validation of this software is necessary to indicate which situations are appropriate for analysis and define existing limitations.Item Accountable Care in Texas: A Case Study of Scott & White Healthcare(2010-05-01) Yaeger, Arynn N.; Dr. Kristine LykensScott & White Healthcare of Temple is Texas’s only example of an “Accountable Care Organization” (ACO), as described in the national health reform of March 2010. This case study seeks to identify how Scott & White is able to contain costs while maintaining patient health and satisfaction and why they were able to create their unique system. Conclusions were drawn from personal interviews with Scott & White administrators, physicians, and staff, whose responses were analyzed for recurring themes addressing the research questions. This case study concludes that Scott & White promotes accountability by achieving an alignment of incentives: namely, a physician led governance structure and electronic health record, integration with their health plan, and being open to other payers.Item Adaptation of the Genetic Risk Prediction Model BRCAPRO for Primary Care Settings(2017-05-01) Atienza, Philamer M.; Sumihiro Suzuki; Swati Biswas; Karan P. SinghIdentifying women at high risks of carrying the breast cancer susceptibility genes is crucial for providing timely surveillance and necessary health management interventions. BRCAPRO is one of the most widely used statistical models for breast cancer risk prediction in genetic counseling. It provides carrier probabilities of BRCA1/2 mutations and calculates the risks of developing breast and ovarian cancers. This calculation requires extensive personal and family history information, which makes it difficult to use in primary care where a wider population could be reached. Thus, we developed a two-stage approach for the genetic risk prediction of BRCA1/2 mutation. In the first stage, limited information on the counselee and her family history of cancer are used in simplified versions of BRCAPRO. If the risk at this stage is found to be high, the full BRCAPRO model utilizing the complete family history is implemented in the second stage. We aimed to balance the tradeoff between the amount of information used and the accuracy of the predictions. We explored several first stage tools. BRCAPROLYTE uses information on the affected relatives up to the second degree only. BRCAPROLYTE-Plus additionally includes unaffected relatives by imputing their ages. BRCAPROLYTE-Simple eliminates the need to collect information on the numbers and types of unaffected relatives and imputes them and their ages instead. The study cohorts include 1,917 families mostly at high risk from the Cancer Genetics Network, 796 high-risk families from MD Anderson Cancer Center, and 1,344 population-based families from Newton-Wellesley Hospital. To evaluate the models, we used sensitivity, specificity, area under the curve, and observed versus expected number of carriers. We also considered clinical criteria of number of referrals made by each model. We found the proposed two-stage approach (with BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple at the first stage) has very limited loss of discrimination and comparable calibration with BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. Thus, our two-stage approach allows for practical large-scale genetic risk assessment in primary care.