Hemic and Immune Systems Commons^™

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

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

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

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

MaineHealth 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

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, …

The Role Of Neighborhood Characteristics In Late Stage Melanoma Diagnosis Among Hispanic Men In California, Texas, And Florida, 1996-2012, Valerie M. Harvey, Clinton W. Enos, Jarvis T. Chen, Hadiza Galadima, Karl Eschbach

Community & Environmental Health Faculty Publications

Background. Hispanics diagnosed with cutaneous melanoma are more likely to present at advanced stages but the reasons for this are unknown. We identify census tracts at high risk for late stage melanoma diagnosis (LSMD) and examine the contextual predictors of LSMD in California, Texas, and Florida. Methods. We conducted a cross-sectional study using geocoded state cancer registry data. Using hierarchical multilevel logistic regression models we estimated ORs and 95% confidence intervals for the impact of socioeconomic, Hispanic ethnic concentration, index of dissimilarity, and health resource availability measures on LSMD. Results. We identified 12,493 cases. In California, late …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Abcb5 Identifies Immunoregulatory Dermal Cells, Tobias Schatton, Jun Yang, Sonja Kleffel, Mayuko Uehara, Steven R. Barthel, Christoph Schlapbach, Qian Zhan, Stephen Dudeney, Hansgeorg Mueller, Nayoung Lee, Juliane C. De Vries, Barbara Meier, Seppe Vander Beken, Mark M. Kluth, Christoph Ganss, Arlene H. Sharpe, Ana Maria Waaga-Gasser, Mohamed H. Sayegh, Reza Abdi, Karin Scharffetter-Kochanek, George F. Murphy, Thomas S. Kupper, Natasha Y. Frank, Markus H. Frank

Research outputs 2014 to 2021

Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of …

Nanotoxicity In Cells Of The Immune System, Jonathan J. Pelc

Science Scholars

Nanoparticles (NPs) provide a new medical approach to drug therapy. As with every new approach, safety precautions need to be taken, and the immediate and long-term effects for many NPs are still unclear. When administering a medical treatment into the human body, the first issue that needs to be addressed is host detection of the medicine and inflammation as a possible result of the treatment. If a new NP treatment causes inflammation before it releases its medicine, that treatment may be ineffective, even damaging to the patient. Small metallic and organic particles have been shown to elicit an inflammatory responses …

Cxcr7 Expression Disrupts Endothelial Cell Homeostasis And Causes Ligand-Dependent Invasion, Jennifer Totonchy, Lisa Clepper, Kevin G. Phillips, Owen J. T. Mccarty, Ashlee V. Moses

Pharmacy Faculty Articles and Research

The homeostatic function of endothelial cells (EC ) is critical for a number of physiological processes including vascular integrity, immunity, and wound healing. Indeed, vascular abnormalities resulting from EC dysfunction contribute to the development and spread of malignancies. The alternative SDF-1/CXCL12 receptor CXCR7 is frequently and specifically highly expressed in tumor-associated vessels. In this study, we investigate whether CXCR7 contributes to vascular dysfunction by specifically examining the effect of CXCR7 expression on EC barrier function and motility. We demonstrate that CXCR7 expression in EC results in redistribution of CD31/PECAM-1 and loss of contact inhibition. Moreover, CXCR7+ EC are deficient in …

Disposable Platform Provides Visual And Color-Based Point-Of-Care Anemia Self-Testing, Erika A. Tyburski, Scott E. Gillespie, William A. Stoy, Robert G. Mannino, Alexander J. Weiss, Alexa F. Siu, Rayford H. Bulloch, Karthik Thota, Anyela Cardenas, Wilena Session, Hanna J. Khoury, Siobhán O'Connor, Silvia T. Bunting, Jeanne Boudreaux, Craig R. Forest, Manila Gaddh, Traci Leong, L. Andrew Lyon, Wilbur A. Lam

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, standalone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels.

METHODS. We tested blood from 238 pediatric and adult patients with anemia of varying …

Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes …

Acute Myeloid Leukaemia In Children: Experience At A Tertiary Care Facility Of Pakistan, Zehra Fadoo, Naureen Mushtaq, Saima Alvi, Muhammad Ali

Department of Paediatrics and Child Health

Objective: To document the demographics and outcome of children with Acute Myeloid Leukemia (AML) treated at a tertiary care facility of Pakistan.

Methods: A retrospective study was conducted at Aga Khan University on children (less than 15 years) diagnosed to have AML between January 2000 to May 2007.Total 40 cases were diagnosed out of which 37 charts were available for review.

Results: The average age of presentation was 8.5±4.5 years and 75% were males. The most common presenting feature was fever in 83% followed by bleeding in 41% and pallor in 39%. Initial WBC of > 100,000 was seen in 19% …

Cytomegalovirus Cc Chemokine Promotes Immune Cell Migration, Jennifer Totonchy, Michael Denton, Craig N. Kreklywich, Takeshi Andoh, Jessica M. Osborn, Daniel Chen, Ilhem Messaoudi, Susan L. Orloff, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture …

Hcmv Pus28 Initiates Pro-Migratory Signaling Via Activation Of Pyk2 Kinase, Jennifer Totonchy, Susan Varnum, Ryan Melnychuk, Patricia Smith, Ljiliana Pasa-Tolic, Janani I. Shutthanadan, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Background: Human Cytomegalovirus (HCMV) has been implicated in the acceleration of vascular disease and chronic allograft rejection. Recently, the virus has been associated with glioblastoma and other tumors. We have previously shown that the HCMV-encoded chemokine receptor pUS28 mediates smooth muscle cell (SMC) and macrophage motility and this activity has been implicated in the acceleration of vascular disease. pUS28 induced SMC migration involves the activation of the protein tyrosine kinases (PTKs) Src and Focal adhesion kinase as well as the small GTPase RhoA. The PTK Pyk2 has been shown to play a role in cellular migration and formation of cancer, …