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Hemic and Immune Systems

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Articles 1 - 30 of 52

Full-Text Articles in Anatomy

Ikaros Expression Drives The Aberrant Metabolic Phenotype Of Macrophages In Chronic Hiv Infection, Cecilia Vittori, Celeste Faia, Dorota Wyczechowska, Amber Trauth, Karlie Plaisance-Bonstaff, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi Jan 2024

Ikaros Expression Drives The Aberrant Metabolic Phenotype Of Macrophages In Chronic Hiv Infection, Cecilia Vittori, Celeste Faia, Dorota Wyczechowska, Amber Trauth, Karlie Plaisance-Bonstaff, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

The increased risk for acquiring secondary illnesses in people living with HIV (PLWH) has been associated with immune dysfunction. We have previously found that circulating monocytes from PLWH display a trained phenotype. Here, we evaluated the metabolic profile of these cells and found increased mitochondrial respiration and glycolysis of monocyte-derived macrophages (MDMs) from PLWH. We additionally found that cART shifted the energy metabolism of MDMs from controls toward increased utilization of mitochondrial respiration. Importantly, both downregulation of IKAROS expression and inhibition of the mTOR pathway reversed the metabolic profile of MDMs from PLWH and cART-treated control-MDMs. Altogether, this study reveals …


Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba Jan 2024

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …


Characterization Of Epithelial Growth Factor Transcripts Identified In Crotalus Atrox Venom, Ivan Lopez, Ying Jia Sep 2023

Characterization Of Epithelial Growth Factor Transcripts Identified In Crotalus Atrox Venom, Ivan Lopez, Ying Jia

Research Symposium

Epithelial Growth Factor (EGF) is the primary source in regeneration and stimulation of essential fibroblasts cells commonly found in epithelium. Studies have shown that snake venom components are becoming a growing factor in treating illnesses such as cancer, muscular dystrophy, chronic pain, blood pressure, blood clotting, etc. EGF in human cells contains a promising quaternary structure that can bind to snake venom metalloproteinases, proposing a means of activating biochemical responses through protein-protein interactions to regulate unwanted cellular functions. This supports promising research in achieving a greater understanding of regulation along cellular pathways through ligands, increasing the likelihood of targeting unwanted …


Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr Sep 2023

Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr

School of Dentistry Faculty Publications

Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence Candida species, that is, Candida dubliniensis, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1(+) polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1(+) leukocytes. Compared to nonimmunized control mice, we observed increased levels …


Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder Jun 2023

Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder

School of Graduate Studies Faculty Publications

Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …


Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang Feb 2023

Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang

School of Public Health Faculty Publications

Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.


Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov Jan 2023

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …


Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese Jul 2022

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …


Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters Mar 2022

Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters

Pharmacy and Wellness Review

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the deterioration of the myelin sheath, causing axonal damage which leads to debilitating symptoms. Most therapies for the treatment of MS, including daclizumab, primarily target relapsing-remitting multiple sclerosis (RRMS), a form of MS where patients experience periods of exacerbated symptoms as well as intermittent periods of remission. Daclizumab is a humanized monoclonal antibody that is administered as a once monthly subcutaneous injection. The SELECT trilogy of trials have been instrumental in providing safety and efficacy data for daclizumab. The DECIDE study was the first randomized controlled …


Attenuated Negative Feedback In Monocyte-Derived Macrophages From Persons Living With Hiv: A Role For Ikaros, Celeste Faia, Karlie Plaisance-Bonstaff, Cecilia Vittori, Dorota Wyczechowska, Adam Lassak, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi Nov 2021

Attenuated Negative Feedback In Monocyte-Derived Macrophages From Persons Living With Hiv: A Role For Ikaros, Celeste Faia, Karlie Plaisance-Bonstaff, Cecilia Vittori, Dorota Wyczechowska, Adam Lassak, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14+ monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals (TNFA, IL6, IL1B, miR-155-5p, and IDO1) dominate over negative feedback signals (NCOR2, …


May-Thurner Compressive Syndrome Unmasked By Rapid Weight Loss, Hesham A. Hassan, Jan-Paul Sambataro, James C. Abraham Jun 2021

May-Thurner Compressive Syndrome Unmasked By Rapid Weight Loss, Hesham A. Hassan, Jan-Paul Sambataro, James C. Abraham

HCA Healthcare Journal of Medicine

May-Thurner Syndrome (MTS) is an anatomical syndrome characterized by a predisposition to clot formation when there is compression of the left iliac vein by the right iliac artery. In this case, we discuss an atypical presentation of MTS in a young male after rapid weight loss. The patient was admitted for an unprovoked massive proximal deep vein thrombosis (DVT) after a two-hundred-pound weight loss during the preceding six-month period. Treatment involved mechanical thrombectomy by interventional radiology, initiation of apixaban and recommended follow up with vascular surgery for angioplasty instead of immediate stent placement.


Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson May 2021

Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson

Research Days

Background: Our center receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurately interpreting lab results. Bhasin et al showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little published about the referral patterns to pediatric hematology and the outcomes of these referrals.

Objectives/Goal: To characterize our hematology referrals for bleeding disorder …


Effect Of He Plasma Jet Versus Surface Plasma On The Metabolites Of Acute Myeloid Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Wenjie Xia, Hai-Lan Chen, Michael G. Kong Jan 2021

Effect Of He Plasma Jet Versus Surface Plasma On The Metabolites Of Acute Myeloid Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Wenjie Xia, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and …


Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra Jan 2021

Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra

Biological Sciences Faculty Publications

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting …


In Vitro Immune Activation By Treponema Pallidum And The Effect On Osteoclastogenesis: First Experimental Step Towards An Integration Between Osteoimmunology And Paleopathology., Emily Ann Rich May 2020

In Vitro Immune Activation By Treponema Pallidum And The Effect On Osteoclastogenesis: First Experimental Step Towards An Integration Between Osteoimmunology And Paleopathology., Emily Ann Rich

College of Arts & Sciences Senior Honors Theses

The presence of pathogens in the human body influences the expression of pro-inflammatory cytokines by activated immune cells. These cytokines, and other factors, regulate osteoclastogenesis and osteoclast activity. Through experimental osteoimmunology, interactions between the inflammatory response and bone cell physiology may provide insight into how immune processes can be translated into the lesions or abnormalities observed in the osteological record. In this research, our objective was to determine if the cytokines produced by activated immune cells increase osteoclastogenesis and osteoclast activity. To evaluate this hypothesis, we used two main protocols, one for immune activation and one for osteoclastogenesis, that utilized …


Nuclear Magnetic Resonance Solution Structure And Functional Behavior Of The Human Proton Channel, Monika Bayrhuber, Innokentiy Maslennikov, Witek Kwiatkowski, Alexander Sobol, Christoph Wierschem, Cédric Eichmann, Lukas Frey, Roland Riek Jul 2019

Nuclear Magnetic Resonance Solution Structure And Functional Behavior Of The Human Proton Channel, Monika Bayrhuber, Innokentiy Maslennikov, Witek Kwiatkowski, Alexander Sobol, Christoph Wierschem, Cédric Eichmann, Lukas Frey, Roland Riek

Pharmacy Faculty Articles and Research

The human voltage-gated proton channel [Hv1(1) or VSDO(2)] plays an important role in the human innate immune system. Its structure differs considerably from those of other cation channels. It is built solely of a voltage-sensing domain and thus lacks the central pore domain, which is essential for other cation channels. Here, we determined the solution structure of an N- and C-terminally truncated human Hv1 (Δ-Hv1) in the resting state by nuclear magnetic resonance (NMR) spectroscopy. Δ-Hv1 comprises the typical voltage-sensing antiparallel four-helix bundle (S1–S4) preceded by an amphipathic helix (S0). The solution structure corresponds to an intermediate …


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang Jul 2019

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …


Lipoprotein(A) Plasma Levels, Bone Mineral Density And Risk Of Hip Fracture: A Post Hoc Analysis Of The Women's Health Initiative, Usa, Bernhard Haring, Carolyn J. Crandall, Laura Carbone, Simin Liu, Wenjun Li, Karen C. Johnson, Jean Wactawski-Wende, Aladdin H. Shadyab, Margery L. Gass, Victor Kamensky, Jane A. Cauley, Sylvia Wassertheil-Smoller Jun 2019

Lipoprotein(A) Plasma Levels, Bone Mineral Density And Risk Of Hip Fracture: A Post Hoc Analysis Of The Women's Health Initiative, Usa, Bernhard Haring, Carolyn J. Crandall, Laura Carbone, Simin Liu, Wenjun Li, Karen C. Johnson, Jean Wactawski-Wende, Aladdin H. Shadyab, Margery L. Gass, Victor Kamensky, Jane A. Cauley, Sylvia Wassertheil-Smoller

Wenjun Li

OBJECTIVES: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women.

DESIGN: Post hoc analysis of data from the Women's Health Initiative (WHI), USA.

SETTING: 40 clinical centres in the USA.

PARTICIPANTS: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and …


Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak Mar 2019

Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak

Katherine A. Fitzgerald

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS/STING, and …


Role Of T-Bet In Production Of Immunoglobulin Isotypes In An Influenza Setting, David Sidhom Jan 2019

Role Of T-Bet In Production Of Immunoglobulin Isotypes In An Influenza Setting, David Sidhom

Honors Undergraduate Theses

Influenza is one of the most common diseases worldwide, yet the vaccines against influenza are only 35% effective at protecting against infection. Creating a more effective vaccine requires an understanding of the foundation and the factors that contribute to a strong and protective adaptive immune response. T-bet [TBX21] is a transcription factor that plays an instrumental role in the orchestration of the type 1 immune response, which is the specialized response used by the immune system for a cell-mediated response against intracellular pathogens, such as influenza. It has yet to be explored in an influenza setting on the role T-bet …


Immune Checkpoints In Cancer Treatment, Matthew A. Cherubino Oct 2018

Immune Checkpoints In Cancer Treatment, Matthew A. Cherubino

Student Publications

Despite the human immune system, cancer thrives in an extremely hostile environment. Cancer is the second most common cause of death in the U.S. with about 600,000 deaths every year, and cancer is expected to surpass heart disease as the most common cause of death in the U.S. Immune checkpoint inhibitors are a novel and promising therapeutic for treating cancer in its late stages.


Ebola: Africa, James Goodwin May 2018

Ebola: Africa, James Goodwin

Global Issues in Public Health

In this paper, I talk about the Ebola Hemorrhagic Fever. Ebola is a rare virus that spreads through the immune system and can be fatal. Ebola is a pathogen from Africa, specifically West Africa. There has been almost 32,000 cases since 1976. Symptoms include, Fever, Headache, Muscle pain, Fatigue, Diarrhea, Vomiting, Stomach pain, and Bleeding/Bruising. Transmission happens during close or direct contact. World Health Organization has been making efforts to handle outbreaks such as the outbreak in 2014. World Health Organization mobilized and set up relief efforts. Education is a key idea for my thoughts on how we can intervene …


The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha May 2018

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …


Immunodeficient R2g2 Mouse Strain Yields Spleens With Unusual Cytoarchitecture And Sympathetic Innervation, Nicholas Mason Britt, Madeleine Kate Miller, Donald B. Hoover Ph.D., John B. Schweitzer M.D. Apr 2018

Immunodeficient R2g2 Mouse Strain Yields Spleens With Unusual Cytoarchitecture And Sympathetic Innervation, Nicholas Mason Britt, Madeleine Kate Miller, Donald B. Hoover Ph.D., John B. Schweitzer M.D.

Appalachian Student Research Forum

The nervous system and immune system contact one another through two-way communication in order to establish and preserve homeostasis. The sympathetic neurotransmitter norepinephrine has an impact on how the immune system responds by affecting regional blood flow and activation of adrenergic receptors on leukocytes. Former studies showed that immune cells are capable of releasing nerve growth factor allowing for the establishment and continuation of sympathetic nerves in targeted tissues. From this gathered information, it was hypothesized that sympathetic nerves would prove to be less frequent in spleens from the immunodeficient R2G2 mouse strain (Envigo) when compared to 129P3/J (129) and …


Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack Jan 2018

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …


Delaying The Start Of Iron Until 28 Days After Antimalarial Treatment Is Associated With Lower Incidence Of Subsequent Illness In Children With Malaria And Iron Deficiency., Ericka Jaramillo, Ezekiel Mupere, Robert Opoka, James Hodges, Troy Lund, Michael Georgieff, Chandy John, Sarah Cusick Dec 2017

Delaying The Start Of Iron Until 28 Days After Antimalarial Treatment Is Associated With Lower Incidence Of Subsequent Illness In Children With Malaria And Iron Deficiency., Ericka Jaramillo, Ezekiel Mupere, Robert Opoka, James Hodges, Troy Lund, Michael Georgieff, Chandy John, Sarah Cusick

Paediatrics and Child Health, East Africa

We evaluated the incidence of all-cause and malaria-specific clinic visits during follow-up of a recent trial of iron therapy. In the main trial, Ugandan children 6–59 months with smearconfirmed malaria and iron deficiency [zinc protoporphyrin (ZPP > = 80 μmol/mol heme)] were treated for malaria and randomized to start a 27-day course of oral iron concurrently with (immediate group) or 28 days after (delayed group) antimalarial treatment. All children were followed for the same 56-day period starting at the time of antimalarial treatment (Day 0) and underwent passive and active surveillance for malaria and other morbidity for the entire follow-up period. …


Cerebrospinal Fluid Kynurenine And Kynurenic Acid Concentrations Are Associated With Coma Duration And Long-Term Neurocognitive Impairment In Ugandan Children With Cerebral Malaria, Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert Opoka, Paul Bangirana, Carl Sellgren, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy John Dec 2017

Cerebrospinal Fluid Kynurenine And Kynurenic Acid Concentrations Are Associated With Coma Duration And Long-Term Neurocognitive Impairment In Ugandan Children With Cerebral Malaria, Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert Opoka, Paul Bangirana, Carl Sellgren, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy John

Paediatrics and Child Health, East Africa

Background: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated.

Methods: Cerebrospinal fuid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to …


When Is Affect Variability Bad For Health? The Association Between Affect Variability And Immune Response To The Influenza Vaccination, Brooke N. Jenkins, John F. Hunter, Marie P. Cross, Amanda M. Acevedo, Sarah D. Pressman Nov 2017

When Is Affect Variability Bad For Health? The Association Between Affect Variability And Immune Response To The Influenza Vaccination, Brooke N. Jenkins, John F. Hunter, Marie P. Cross, Amanda M. Acevedo, Sarah D. Pressman

Psychology Faculty Articles and Research

Objectives—This study addresses methodological and theoretical questions about the association between affect and physical health. Specifically, we examine the role of affect variability and its interaction with mean levels of affect to predict antibody (Ab) levels in response to an influenza vaccination.

Methods—Participants (N = 83) received the vaccination and completed daily diary measures of affect four times a day for 13 days. At one and four months post-vaccination, blood was collected from the participants to assess Ab levels.

Results—Findings indicate that affect variability and its interaction with mean levels of affect predict an individual’s immune response. …


Improving Type And Screen Specimen Collection Prior To Elective Surgery, Nordx Blood Bank Staff, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman Aug 2017

Improving Type And Screen Specimen Collection Prior To Elective Surgery, Nordx Blood Bank Staff, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman

Maine Medical Center

To avoid delays in the availability of compatible blood for elective surgery patients requiring transfusion, a type and screen specimen should be completed at least 24 hours prior to surgery. Baseline metrics in an acute care inpatient blood bank demonstrated a significant number of cases with no type or screen completed.

The objective of this KPI was to prevent any delays in providing compatible blood products to scheduled surgical patients. Several internal and external system issues were identified as a result of a root cause analysis and a number of actions were initiated.

Outcomes have been positive. Data collection post …


Namibia : Hiv As A National Issue, Elisabeth Vlasak Jan 2017

Namibia : Hiv As A National Issue, Elisabeth Vlasak

Global Public Health

Namibia is located on the southwestern coast of Africa, bordering Angola, Botswana, Zambia, South Africa, and the Atlantic Ocean. Namibia has a population of 2,265,000, as of 2016. Namibia has many challenges, including food insecurity and malnutrition, access to health services, unequal distribution of wealth, but HIV/AIDS is one of the country’s leading challenges. It is estimated that the overall adult infection rate of HIV/AIDS is 15.4% and it is the leading cause of death in Namibia. Adults ages 18-24 are the most at-risk for the disease. Some of the major risk factors are declining condom use, misinformation, social stigma, …