Matching Items (251)
Description
Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
Introduction/Purpose: the purpose of this study was to explore the perception of care after stillbirth and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief in women of racial/ethnic minority who have experienced stillbirth.
Methods: This was an exploratory qualitative research study. Participants were African American, Hispanic, Asian, and American Indian women, between the ages of 26 and 38, who have experienced stillbirth within the past 3 years. Participants completed a 20-30 minute phone interview.
Results: Fourteen women participated in the study (M age = 31.02 ± 5.97 years; M time since stillbirth = 1.47 ± 0.94 years). Women’s perceptions about physical activity and mindfulness to cope with grief were coded into the following major themes: perception of health care after stillbirth (satisfaction with the level of care provided), recommendations about inter-conception health care from physician (relating to mental, emotional, and physical health), grief (comfort with communicating with the physician), coping mechanisms, perception of the relationship between physical activity and mood, barriers to participating in physical activity (social and behavioral), pre-pregnancy physical activity, and perception of mindful approach (e.g., yoga) as a coping mechanism.
Conclusion: This was the first study to explore perceptions of health care and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief after stillbirth in women of racial/ethnic minority. Findings from this study may help inform health care professionals alter their care practices and introduce physical activity and mindfulness based approaches as coping mechanisms to mothers of stillborn babies.
Methods: This was an exploratory qualitative research study. Participants were African American, Hispanic, Asian, and American Indian women, between the ages of 26 and 38, who have experienced stillbirth within the past 3 years. Participants completed a 20-30 minute phone interview.
Results: Fourteen women participated in the study (M age = 31.02 ± 5.97 years; M time since stillbirth = 1.47 ± 0.94 years). Women’s perceptions about physical activity and mindfulness to cope with grief were coded into the following major themes: perception of health care after stillbirth (satisfaction with the level of care provided), recommendations about inter-conception health care from physician (relating to mental, emotional, and physical health), grief (comfort with communicating with the physician), coping mechanisms, perception of the relationship between physical activity and mood, barriers to participating in physical activity (social and behavioral), pre-pregnancy physical activity, and perception of mindful approach (e.g., yoga) as a coping mechanism.
Conclusion: This was the first study to explore perceptions of health care and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief after stillbirth in women of racial/ethnic minority. Findings from this study may help inform health care professionals alter their care practices and introduce physical activity and mindfulness based approaches as coping mechanisms to mothers of stillborn babies.
ContributorsArvayo, Jordan Michelle (Author) / Huberty, Jennifer (Thesis director) / Hoffner, Kristin (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
Bacteria play a vital role in the world ecosystem, more importantly human health and disease. The capability to differentiate and identify these microorganisms serves as an important research objective. In past years, separations-based approaches have served as a way to observe and identify bacteria based on their characteristics. Gradient insulator dielectrophoresis (g-iDEP) provides benefits in identifying serotypes of a single species with precise separation. Separation of Staphylococcus epidermidis in a single g-iDEP microchannel is conducted exploiting their electrophoretic and electrokinetic properties. The cells were captured and concentrated at gates with interacting forces within the microchannel to clearly distinguish between the two strains. These results provide support for g-iDEP serving as a separating method and, furthermore, future clinical applications.
ContributorsDavis, Paige Elizabeth (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / Jones, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
This study examined the effect of an 8-week exercise intervention on functional exercise capacity in adolescents with Down syndrome (DS). Forty participants were randomly assigned to one of three groups: assisted cycling (ACT) (n = 17) where participants experienced at least a 35% increase in their voluntary cycling speed through the use of a motor, voluntary cycling (VC) (n = 15) where participants cycled at a self-selected cadence, and no cycling (NC) (n = 8) where participants did not participate in any cycling intervention. In each cycling intervention, each participant completed three, 30 minute cycling sessions per week for a total of eight weeks. The Six-Minute Walk Test (6MWT) was administered prior to and after the 8-week intervention in pre-test and post-test assessment sessions, respectively. Our hypothesis was somewhat supported in that functional exercise capacity improved after ACT as measured by an increase in total number of laps walked, total distance walked, and average walking speed during the 6MWT, when compared to VC or NC.
ContributorsCook, Megan Rey (Author) / Ringenbach, Shannon (Thesis director) / Huberty, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Background: High risk types of human papillomavirus (HPV) are known to cause cancer, including cervical (99%) and oropharyngeal cancer (70%). HPV type 16 is the most common subtype. Three antigens that are critical for integration or tumor progression are E2, E6 and E7. In this study, we developed a systematic approach to identify naturally-processed HPV16-derived HLA class I epitopes for immunotherapy development. Methods: K562 cells, which lack HLA expression, were transduced with each HPV16 antigen using lentivirus and supertransfected with HLA-A2 by nucleofection. Stable cell lines expressing each antigen were selected for and maintained throughout the investigation. In order to establish a Gateway-compatible vector for robust transient gene expression, a Gateway recombination expression cloning cassette was inserted into the commercial Lonza pMAX GFP backbone, which has been experimentally shown to display high transfection expression efficiency. GFP was cloned into the vector and plain K562 cells were transfected with the plasmid by nucleofection. Results: Expression of K562-A2 was tested at various time points by flow cytometry and A2 expression was confirmed. Protein expression was shown for the transduced K562 E7 by Western blot analysis. High transfection efficiency of the pMAX_GFP_Dest vector (up to 97% GFP+ cells) was obtained 48 hours post transfection, comparable to the commercial GFP-plasmid. Conclusion: We have established a rapid system for target viral antigen co-expression with single HLA molecules for analysis of antigen presentation. Using HPV as a model system, our goal is to identify specific antigenic peptide sequences to develop immunotherapeutic treatments for HPV-associated cancers.
ContributorsVarda, Bianca Marie (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / Krishna, Sri (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.
ContributorsHayden, Joel James (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
Objective: Fewer than 50% of female college freshmen meet physical activity (PA) guidelines. Innovative approaches that help college women increase their PA are warranted. The study purpose was to pilot test a magazine-based discussion group for improving PA, self-worth, and nutrition behaviors in freshmen college females. Method: Thirty-seven women (18-20 years) were randomized to intervention (n=17) and control (n=20) groups. The intervention group participated in an 8-week magazine-based discussion group adapted from a previously tested social cognitive theory based intervention, Fit Minded. Excerpts from a popular women's health magazine were discussed during weekly meetings incorporating PA, self-worth and nutrition education. The control group did not attend meetings, but received the magazines. Outcomes and feasibility measures included: self-reported PA, general self-worth, knowledge self-worth, self-efficacy, social support, and daily fruits, vegetables, junk food, sugar-sweetened beverage consumption. Results: Twelve participants from the intervention group attended more than 75% of meetings. A time effect was observed for PA (p=0.001) and family social support (p=0.002). Time x group effects were observed for PA (p=0.001), general self-worth (p=0.04), knowledge self-worth (p=0.03), and daily sugar-sweetened beverage consumption (p=0.03), with the intervention group reporting greater increases in PA, general self-worth and knowledge self-worth and greater decreases in daily sugar-sweetened beverage consumption. Although not significant, the intervention group demonstrated positive trends in self-efficacy, friend social support and fruit and veggie consumption as compared to the control group. Conclusion: A magazine-based discussion group may provide a promising platform to improve PA, self-worth and nutrition behaviors in female college freshmen.
ContributorsPellitteri, Katelyn (Author) / Huberty, Jennifer (Thesis director) / Bruening, Meg (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Social Transformation (Contributor) / Sandra Day O'Connor College of Law (Contributor)
Created2014-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05