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- All Subjects: healthcare
- All Subjects: Immunology
- Creators: School of Life Sciences
- Creators: College of Health Solutions
Description
Introduction: Human papillomavirus (HPV) infection is seen in up to 90% of cases of cervical cancer, the third leading cancer cause of death in women. Current HPV screening focuses on only two HPV types and covers roughly 75% of HPV-associated cervical cancers. A protein based assay to test for antibody biomarkers against 98 HPV antigens from both high and low risk types could provide an inexpensive and reliable method to screen for patients at risk of developing invasive cervical cancer. Methods: 98 codon optimized, commercially produced HPV genes were cloned into the pANT7_cGST vector, amplified in a bacterial host, and purified for mammalian expression using in vitro transcription/translation (IVTT) in a luminescence-based RAPID ELISA (RELISA) assay. Monoclonal antibodies were used to determine immune cross-reactivity between phylogenetically similar antigens. Lastly, several protein characteristics were examined to determine if they correlated with protein expression. Results: All genes were successfully moved into the destination vector and 86 of the 98 genes (88%) expressed protein at an adequate level. A difference was noted in expression by gene across HPV types but no correlation was found between protein size, pI, or aliphatic index and expression. Discussion: Further testing is needed to express the remaining 12 HPV genes. Once all genes have been successfully expressed and purified at high concentrations, DNA will be printed on microscope slides to create a protein microarray. This microarray will be used to screen HPV-positive patient sera for antibody biomarkers that may be indicative of cervical cancer and precancerous cervical neoplasias.
ContributorsMeshay, Ian Matthew (Author) / Anderson, Karen (Thesis director) / Magee, Mitch (Committee member) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Emerging Information Technology, Storage and Evaluation within Healthcare: A Discerning IMT Analysis
Description
The introduction of novel information technology within contemporary healthcare settings presents a critical juncture for the industry and thus lends itself to the importance of better understanding the impact of this emerging "health 2.0" landscape. Simply, how such technology may affect the healthcare system is still not fully realized, despite the ever-growing need to adopt it in order to serve a growing patient population. Thus, two pertinent questions are posed: is HIT useful and practical and, if so, what is the best way to implement it? This study examined the clinical implementation of specific instances of health information technology (HIT) so as to weigh its benefits and risks to ultimately construct a proposal for successful widespread adoption. Due to the poignancy of information analysis within HIT, Information Measurement Theory (IMT) was used to measure the effectiveness of current HIT systems as well as to elucidate improvements for future implementation. The results indicate that increased transparency, attention to patient-focused approaches and proper IT training will not only allow HIT to better serve the community, but will also decrease inefficient healthcare expenditure.
ContributorsMaietta, Myles Anthony (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Background: Coccidioidomycosis (Valley Fever) is a respiratory disease that is caused by the soil-dwelling fungi Coccidioides immitis and Coccidioides posadasii. Because fungal glycosylation patterns are distinct from mammalian glycosylation patterns, we hypothesized that certain lectins (carbohydrate-binding proteins) might have differential binding properties to coccidioidal glycoproteins, and therefore serve as a tool for the purification and characterization of these glycoproteins from patient specimens. Materials and Methods: To identify potential Coccidioides-binding lectins, lectin-based immunohistochemistry was performed using a panel of 21 lectins on lung tissue from human patients infected with Coccidioides. Enzyme-Linked Immunosorbent Assays (ELISAs) were used to confirm and test candidate Coccidioides-binding lectins for their ability to bind to proteins from antigen preparations of laboratory-grown Coccidioides. Inhibition IHC and ELISAs were used to confirm binding properties of these lectins. SDS-PAGE and mass spectrometry were performed on eluates from coccidioidal antigen preparations run through lectin-affinity chromatography columns to characterize and identify lectin-binding coccidioidal glycoproteins. Results: Two GlcNAc-binding lectins, GSLII and sWGA, bound specifically to spherules and endospores in infected human lung tissue, and not to adjacent lung tissue. The binding of these lectins to both Coccidioides proteins in lung tissue and to coccidioidal antigen preparations was confirmed to have lectin-like characteristics. SDS-PAGE analysis of eluates from lectin-affinity chromatography demonstrated that GSLII and sWGA bind to coccidioidal glycoproteins. Mass spectrometric identification of the top ten lectin affinity-purified glycoproteins demonstrated that GSLII and sWGA share affinity to a common set of coccidioidal glycoproteins. Conclusion: This is the first report of lectins that bind specifically to Coccidioides spherules and endospores in infected humans. These lectins may have the potential to serve as tools for a better method of detection and diagnosis of Valley Fever.
ContributorsChowdhury, Yasmynn (Author) / Lake, Douglas (Thesis director) / Grys, Thomas (Committee member) / Magee, Mitchell (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
Efforts to quantify the diversity of the T cell repertoire have generally been unsuccessful because not all factors accounting for diversity have been considered. In order to get an accurate representation of the T cell repertoire, one must incorporate analysis of germline gene diversity, diversity from somatic recombination, joining diversity from N- and P- nucleotides, and TCR chain pairing diversity. Because of advances in high-throughput sequencing techniques, estimates have been able to account for diversity from TCR genes. However the ability to account for chain pairing diversity has been more difficult. In order to do so, single cell sorting techniques must be employed. These techniques, though effective, are time consuming and expensive. For this reason, no large-scale analyses have been done on the immune repertoires using these techniques. In this study, we propose a novel method for linking the two TCR chain sequences from an individual cell. DNA origami nanostructure technology is employed to capture and bind the TCRγ and TCRδ chain mRNA inside individual cells using probe strands complementary to the C-region of those sequences. We then use a dual-primer RT and ligation molecular strategy to link the two sequences together. The result is a single amplicon containing the CDR3 region of the TCRγ and TCRδ. This amplicon can then be easily PCR amplified using sequence specific primers, and sequenced. DNA origami nanostructures offer a rapid, cost-effective method alternative to conventional single cell sorting techniques, as both TCR mRNA can be captured on one origami molecule inside a single cell. At present, this study outlines a proof-of-principle analysis of the method to determine its functionality. Using known TCRγ and TCRδ sequences, the DNA origami and RT/PCR method was tested and resulting sequence data proved the effectiveness of the method. The original TCRγ and TCRδ sequences were linked together as a single amplicon containing both CDR3 regions of the genes. Thus, this method can be employed in further research to elucidate the γδ T cell repertoire. This technology is also easily adapted to any gene target or cell type and therefore presents a large opportunity to be used in other immune repertoire analysis and other immunological studies (such as the rapid identification and subsequent production of antibodies).
ContributorsPoindexter, Morgan Elizabeth (Author) / Blattman, Joseph (Thesis director) / Yan, Hao (Committee member) / Schoettle, Louis (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (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
The Performance Based Studies Research Studies Group (PBSRG) at Arizona State University aims to evaluate and provide solutions to problems by using concepts derived from deductive logic. The research group identified that problems in most industries are due to the traditional approach of management, direction and control, and offers a practical contrasting model. The author is a biological sciences major interested in the health care industry. As a volunteer at a local non-profit pregnancy clinic in Tempe, AZ, the author noticed characteristics of the clinic structure that resembled both the traditional approach of management, direction and control and the best value (BV) approach. Although the pregnancy clinic has existed for 30 years and has high patient satisfaction, it faces problems that jeopardize its long term sustainability. This study analyzes the stereotypical structure of non-profit health clinics through literature review and through a case study of a local non-profit pregnancy clinic in Tempe, Arizona. The study identified and analyzed the factors that contribute to inefficiency within non-profit health clinics. The conclusions of the research demonstrate that characteristics of non-profit health clinics that resemble the traditional model perform in a manner that is unsustainable. Recommendations were based on concepts derived from Information Measurement Theory (IMT) and aimed to improve efficiency and effectiveness. The study identifies sources of risks and examines the performance of such organizations; the study concludes that rejection of traditional models and adaptation of the new approach is preferable in improving performance and increasing patient, employee, and volunteer satisfaction.
ContributorsTran, Yvonne Ho (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Viral infections are a significant cause of disease in humans. While some viral diseases have been eliminated, many more continue to infect millions. Viral infections are challenging to treat because viruses use host cell machinery to replicate, so it is difficult to develop drugs that can target viruses. Normally, the host’s immune system is capable of destroying the virus, but during chronic infections it becomes exhausted and T cells lose their effector functions necessary for the clearance of the virus. IL-2 can help relieve this exhaustion, but causes toxicity to the body. In mice infected with chronic LCMV, IL-2 administration causes death due to pulmonary hemorrhage. CD4 deficient mice were infected with chronic LCMV and then dosed with IL-2 and survived, but mice that were deficient for CD8 T cells died, indicating that toxicity was mediated by CD8 T cells. CD8 T cells can kill infected host cells directly by producing perforin, or can produce cytokines like IFN-γ and TNF to further activate the immune system and mediate killing. Mice that were deficient in perforin died after IL-2 administration, as well as mice that were deficient in IFN-γ. Mice deficient in TNF, however, survived, indicating that TNF was mediating the toxicity in response to IL-2. There are two different receptors for TNF, p55 and p75. p55 is known as TNFR1 and has been implicated in apoptosis of virally infected cells. P75 is known as TNFR2 and is associated more with inflammation in response to infection. My hypothesis was that if TNFR2 was knocked out, infected mice would survive IL-2 dosing. When single knockouts of TNFR1 and 2 were used in an experiment however, it was found that either receptor is capable of mediating toxicity, as both experimental groups failed to survive. This is relevant to current IL-2 therapies because there is no way to eliminate a single receptor in order to reduce toxicity. Further studies exploring the anti-viral capabilities of IFN-γ are suggested.
ContributorsJarvis, Jordan Alisa (Author) / Blattman, Joseph (Thesis director) / Denzler, Karen (Committee member) / McAfee, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Healthcare systems and health insurance are both concepts implemented in every country to provide access to the general population. Countries undergo healthcare reforms in order to increase the performance of the system. In 2010, the Affordable Care Act (ACA) was introduced in the United States to increase coverage and create a more inclusive health insurance market. For comparison, the recent reforms in Chile and Singapore were observed as points to determine what concepts work well and what can be implemented in the U.S. system. Unlike the United States, Chile and Singapore completely altered the system that was previously in use. In Chile, the reforms began in the 1970s and made two more major changes in 1973 and early 2000s. Singapore began its reform in the 1960s and created the medical savings account system that is still in use today. To analyze the system further, the medical professions of neurology, physician assistants and optometry were compared in each country. In regards to neurology, the coverage of services in Chile and Singapore are similar in that select medical procedures are covered. In contrast, the United States offers coverage on a case-by-case basis. For physician assistants, such a profession does not exist in Chile or Singapore. In the United States, the profession is rapidly expanding, and coverage is offered for most services provided. Optometry is a stand-alone profession in both the U.S. and Singapore. The services provided by the optometrists are selectively covered by insurance, depending on whether it is considered a medical problem. Chile covers the services often provided by optometrists, however, the ophthalmologist is the provider, as optometry does not exist. This study concluded that the U.S. should continue to provide a more inclusive healthcare system that includes vision and dental care. The U.S., like Singapore, should also adopt a more integrative system. Under this system, patient care would be provided in a way that professionals specializing in the care are included in every step of the process.
ContributorsLa, Jenny (Co-author) / Feruj, Farihah (Co-author) / Morrison, Sarah (Co-author) / Gaughan, Monica (Thesis director) / Essary, Alison (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The Community Action Research Experiences (CARE) Program collaborated with the WellCare Foundation (WCF) to assess the referral sources of the clinic in order to more effectively reach additional potential patients. Archival data were analyzed from a 19-month period from the medical records of patients. Also, data were collected from interviews with the case manager of agencies that were a known referral source of WCF. These case manager interviews were completed over a one-month period. For the archival data part of the project, data were collected from 117 patients. Four representatives from community agencies participated in phone interviews. The results indicated that the most common referral sources were word of mouth, followed by community agency referrals. The results also indicated that WCF appears to have served a unique niche that is not served by other non-profit health clinics. These results led to implications for action and direction for future applied research.
ContributorsEbbing, Brittany Gabrielle (Author) / Spinrad, Tracy (Thesis director) / Dumka, Larry (Committee member) / Brougham, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
The focus shift towards Silicon Valley and similar ecosystems in the past decade, the recent boom in startups and entrepreneurship, and the resurgence of venture capital funding is fueling rapid advancement of modern technologies, such as software, biotechnology, and renewable energy. One facet of the growing entrepreneurial landscape features healthcare technology—a field of research centered upon various technical advances in medicine, software, and hardware. Trends in healthcare technology commercialization represent a promising opportunity for disruption in the healthcare industry. The integration of rapidly iterating software with medical research, timed perfectly with the passage of the Affordable Care Act and the boom of venture capital investment in both Big Data and mobile technology, has the healthcare technology primed for explosive growth over the next decade. Investment data indicates that strong public market activity in the past year will continue to fuel venture capital growth in both the biotechnology and digital health sectors, with the potential for multiple large exits by life sciences companies, more than even software, in the coming year.
ContributorsPatel, Nisarg (Co-author) / Yun, Kwanho (Co-author) / Wang, Xiao (Thesis director) / Marchant, Gary (Committee member) / Peck, Sidnee (Committee member) / Barrett, The Honors College (Contributor) / Department of Management (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor)
Created2014-05