Diseases Commons^™

The Pathogenesis Of Natural Killer/T Cell Lymphoma, Bei Jiang

Theses & Dissertations

Extranodal natural killer/T-cell lymphomas (NKTCL) are uncommon lymphomas with poor prognosis. In order to gain a better understanding of the molecular pathogenesis of NKTCL, we obtained and compared the global gene expression profile, global somatic mutation profile, and global methylation profile of normal NK cells, malignant NK cell lines, and NKTCL patient samples. We showed that the JAK-STAT pathway was constitutively activated in NKTCL through the cooperation between activation of signal transducer and activator of transcription proteins (STATs) via activating mutations and inactivation of STAT suppressor protein suppressor of cytokine signaling 6 (SOCS6) through promoter hypermethylation. Activating STAT3 and STAT5B …

A Hypothesis For Using Pathway Genetic Load Analysis For Understanding Complex Outcomes In Bilirubin Encephalopathy, Sean M. Riordan, Douglas C. Bittel, Jean-Baptist Lepichon, Silvia Gazzin, Claudio Tiribelli, Jon F. Watchko, Richard P. Wennberg, Steven Shapiro

Manuscripts, Articles, Book Chapters and Other Papers

© 2016 Riordan, Bittel, Le Pichon, Gazzin, Tiribelli, Watchko, Wennberg and Shapiro.

Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. …

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …

The Role Of Neurovascular Compromise, Autoimmune Antibodies And Neuronal Calcium Sensor Proteins During The Onset And Progression Of Alzheimer's Disease - Linking The Retina With The Brain, Hao Wu

Graduate School of Biomedical Sciences Theses and Dissertations

Alzheimer's disease (AD), the main cause of dementia, is a progressive and irreversible neurodegenerative disease. The pathological hallmarks of the disease include bloodbrain barrier (BBB) breach, neurofibrillary tang les and amyloid plaques. Also, emerging evidence has raised the possibility that instead of a secondary consequence, the neuroinflammation contributes to the development and early progression of AD. However, the mechanism underlying the blood-neural barrier (BNB), chronic inflammation and neuronal degenerative diseases (NDDs) remain to be elucidated.

To explore the role of the chronic inflammation in NDDs and delineate the early steps of these diseases, in vivo drug-induced and transgenic mouse models …

Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.

In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).

We found liver fibrosis (APRI) …

Effects Of Prebiotics On Gut Bacterial Communities And Healing Of Induced Colitis In Mice, Krystyn Elizabeth Davis

Master's Theses

Inflammatory Bowel Diseases (IBD) cause chronic inflammation of the gastrointestinal tract and debilitating symptoms in those suffering from the diseases. After inducing colitis in a mouse model using Dextran Sulfate Sodium (DSS), prebiotics inulin and oligofructose enriched inulin (OEI) were used as treatments to determine their effects on the gut microbial community, physiological healing process, and immune response in the mice after initial inflammation and before subsequent inflammation, or relapse. The treatment with inulin led to an increase in regulatory T cell number, but this increase was not as significant as the increase induced by the OEI. Inulin increased the …

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

Dissertations and Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

Loss Of Exogenous Androgen Dependence By Prostate Tumor Cells Is Associated With Elevated Glucuronidation Potential, Brenna M. Zimmer, Michelle E. Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G. Loughman, Jennifer E. Markham, Javier Seravalli, Joseph J. Barycki, Melanie A. Simpson

Department of Biochemistry: Faculty Publications

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD⁺-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher …

Vinyl Chloride-Diet Interactions In Liver Disease : Potential Roles Of Autophagy And Energy Management., Anna L. Lang

Electronic Theses and Dissertations

Vinyl chloride (VC) is a prevalent environmental toxicant that has been shown to cause liver injury at high, occupational exposures. However, most studies have not addressed interactions of low doses with risk-modifying factors. This study aims to explore low-level VC metabolite exposure interactions with other potential risk-modifying factors and their effect on underlying liver disease. We examined sub-hepatotoxic effects of a VC metabolite (chloroethanol, CE) in two murine models of liver injury using ethanol and lipopolysaccharide (LPS). In both, CE significantly enhanced liver injury when compared to either ethanol or LPS alone. Previous studies have shown an increase in mTOR …

Mir-27a And Mir-27b Regulate Autophagic Clearance Of Damaged Mitochondria By Targeting Pten-Induced Putative Kinase 1 (Pink1), Jaekwang Kim, Fabienne C. Fiesel, Krystal C. Belmonte, Roman Hudec, Wang-Xia Wang, Chaeyoung Kim, Peter T. Nelson, Wolfdieter Springer, Jungsu Kim

Pathology and Laboratory Medicine Faculty Publications

Background: Loss-of-function mutations in PINK1 and PARKIN are the most common causes of autosomal recessive Parkinson’s disease (PD). PINK1 is a mitochondrial serine/threonine kinase that plays a critical role in mitophagy, a selective autophagic clearance of damaged mitochondria. Accumulating evidence suggests mitochondrial dysfunction is one of central mechanisms underlying PD pathogenesis. Therefore, identifying regulatory mechanisms of PINK1 expression may provide novel therapeutic opportunities for PD. Although post-translational stabilization of PINK1 upon mitochondrial damage has been extensively studied, little is known about the regulation mechanism of PINK1 at the transcriptional or translational levels.

Results: Here, we demonstrated that microRNA-27a (miR-27a) and …

Statin Therapy For Elderly Patients Should Be Assessed For Each Individual, Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623-30. doi:10.1016/S0140-6736(02)11600-X

Cellular Minichromosome Maintenance Complex Component 5 (Mcm5) Is Incorporated Into Hiv-1 Virions And Modulates Viral Replication In The Newly Infected Cells., Steven Santos, Yuri Obukhov, Sergei Nekhai, Tatiana Pushkarsky, Beda Brichacek, Michael Bukrinsky, Sergey Iordanskiy

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. …

The Immunomodulatory Role Of Adjuvants In Vaccines Formulated With The Recombinant Antigens Ov-103 And Ov-Ral-2 Against Onchocerca Volvulus In Mice., Jessica A. Hess Ligas, Bin Zhan, April R. Torigian, John B. Patton, Nikolai Petrovsky, Tingting Zhan, Maria Elena Bottazzi, Peter J. Hotez, Thomas R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types …

Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.

METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from …

Can Gait Signatures Provide Quantitative Measures For Aiding Clinical Decision-Making? A Systematic Meta-Analysis Of Gait Variability Behavior In Patients With Parkinson’S Disease, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A disturbed, inconsistent walking pattern is a common feature of patients with Parkinson's disease (PwPD). Such extreme variability in both temporal and spatial parameters of gait has been associated with unstable walking and an elevated prevalence of falls. However, despite their ability to discretise healthy from pathological function, normative variability values for key gait parameters are still missing. Furthermore, an understanding of each parameter's response to pathology, as well as the inter-parameter relationships, has received little attention. The aim of this systematic literature review and meta-analysis was therefore to define threshold levels for pathological gait variability as well as to …

Microrna Mir-155 Is Necessary For Efficient Gammaherpesvirus Reactivation From Latency, But Not For Establishment Of Latency, Rebecca L. Crepeau, Peisheng Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNA-155 (miR-155) has been shown to play significant roles in the immune response, including in the formation of germinal centers (GC) and the development and maturation of T follicular helper (Tfh) cells. There is in vitro evidence to support a critical role for cellular miR-155 and viral miR-155 homologs in the establishment of gammaherpesvirus latency in B cells. We sought to determine the contribution of miR-155 to the establishment and maintenance of latency in vivousing murine gammaherpesvirus (MHV-68) infection. MHV-68-infected mice deficient in miR-155 exhibited decreases in GC B cells and Tfh cells. However, the frequencies of spleen cells …

Glial Cell Involvement In Early Alzheimer's Disease, Rachel Y. De La Torre

PSU McNair Scholars Online Journal

Glial cells, the resident immune cells of the brain, are important for brain health as they represent a critical function both in brain injury as well as in brain development and maintenance. Following brain injury, glia quickly respond by cleaning up neuronal and synaptic debris. In addition to their role as the cleaning cell of the brain, recent research has shown that during development, glia also shape and fine-tune neural connections by eliminating weak synapses fated for removal. However, whether glial cells also continue to remodel synaptic architecture in the adult brain is unclear. Moreover, synaptic pruning and loss are …

Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, Katherine P. Mueller

Lawrence University Honors Projects

DAF-19, the only RFX transcription factor found in C. elegans, is required for the formation of neuronal sensory cilia. Four isoforms of the DAF-19 protein have been reported, and the m86 nonsense (null) mutation affecting all four isoforms has been shown to prevent cilia formation. Transcriptome analyses employing microarrays of L1 and adult stage worms were completed using RNA from daf-19(m86) worms and an isogenic wild type strain to identify additional putative DAF-19 target genes. Using transcriptional fusions with GFP, we compared the expression patterns of several potential gene targets using fluorescence confocal microscopy. Expression patterns were characterized in …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez

Electronic Theses, Projects, and Dissertations

Conventional medical treatments fail to address the underlying problems associated with the damage inflicted by a coronary event. Thus, the long-term prognosis of patients admitted for heart failure is disheartening, with reported survival rates of 25 percent. Recent advances in stem cell research highlight the potential benefits of autologous stem cell transplantation for stimulating repair in heart tissue. However, a majority of those suffering from cardiovascular diseases are older adults whose autologous cells no longer possess optimum functional capacity. Additional work is needed to identify the optimal cell types or conditions that will promote cardiovascular regeneration across all age groups. …

Elevated Mtss1 Expression Associated With Metastasis And Poor Prognosis Of Residual Hepatitis B-Related Hepatocellular Carcinoma, Xiu-Yan Huang, Zi-Li Huang, Bin Xu, Zi Chen

Dartmouth Scholarship

Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear.

Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed.

Reverse Engineering A Kinetic Model Of A Dopaminergic Neuron To Apoptosis, Johnathan Morris

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Models Of Hiv And Hpv Coinfection, Samantha Erwin, Meghna Verma, Vida Abedi, Raquel Hontecillas-Magarzo, Stefan Hoops, Josep Bassaganya-Riera, Stanca M. Ciupe

Biology and Medicine Through Mathematics Conference

No abstract provided.

Low Energy Defibrillation By Synchronization; 90 % Less Energy Compared To One Shock., Flavio H. Fenton, Yanyan Ji, Ilija Uzelac, Niels Otani, Elizabeth M. Cherry

Biology and Medicine Through Mathematics Conference

No abstract provided.

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with …

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale

Theses & Dissertations

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Evidence has demonstrated a profound influence of genetic background on AAA formation. The work presented herein discusses two studies: the first demonstrates how genetic components can enhance the susceptibility to AAA formation and the second demonstrates how ECM degradation enhances AAA progression by influencing inflammatory cell phenotypes. An understanding of the pathways involved in AAA pathogenesis can help not only to identify potential patients at risk of AAA development, a heritable disease in which the incriminating component has yet to be …

Fecal Transplant Vs Vancomycin For Recurrent Clostridium Diffile, Lauren M. Taylor, Todd E. Edwards

Physician Assistant Capstones, 2016 to 2019

Objective: To compare fecal transplant and vancomycin in the treatment of recurrent clostridium difficile to determine which has the higher cure rate. Design: Systematic literature review. Methods: Pubmed, Google Scholar, and TRIP database using the search terms “recurrent clostridium difficile.” Filters were implemented in the Pubmed database including: randomized control trials, English, and published in the past 5 years. Records were screened for RCT with fecal transplant and full-text. Results: van Nood et al. revealed an initial cure rate of 81% for the infusion group, and a re-treated cure rate of 94%, compared to the vancomycin alone group of 31% …

Routine Screening For Abdominal Aortic Aneurysm: Is It For Everyone?, Catherine E. Nowak

Physician Assistant Capstones, 2016 to 2019

Objective: Determine whether routine abdominal ultrasound screening in all men ages 65 and over, not just those who are symptomatic or at risk, would be beneficial in reducing the mortality rate from abdominal aortic aneurysms (AAA). Design: Systematic literature review. Methods: The clinical question investigated is whether routine ultrasound screening of AAA for men over age 65 reduces AAA-related mortality as compared to not routinely screening. Searches were done through PubMed using the keywords: screening, abdominal aortic aneurysm, reduce, and mortality. Citations used by the USPSTF AAA screening guidelines were also added to the literature search. In PubMed, further limitations …