Now showing items 21-40 of 1900

    • UMSOM Holds Virtual Commencement to Celebrate Class of 2020

      University of Maryland, Baltimore. School of Medicine (2020-05-15)
    • Commencement 2020

      Jarrell, Bruce E.; Hogan, Larry J., 1956-; Perman, Jay A.; Yang, Shi (Porter); Phelan, Mary T. (2020-05)
    • Targeting of Intracellular Survival Pathways in Human Prostate Cancer Cells

      Adediran, Samusi; Hussain, Arif, M.D. (2019)
      Although significant advances in the treatment of prostate cancer have been made, advanced prostate cancer is essentially incurable and remains the second leading cause of cancer-related deaths among men in the U.S. The current treatment landscape underscores the fact that additional strategies are needed to improve treatment outcomes of both castration sensitive and castration resistant advanced prostate cancer. Prostate cancer is characterized by a remarkable degree of heterogeneity in terms of its underlying biology and clinical behavior. Although pre-clinical models cannot adequately reflect the varied clinical behavior of prostate cancer, they are important for enhancing our understanding of prostate cancer biology and potentially identifying new therapeutic targets. In this thesis, we undertook the approach of studying several cell culture models of prostate cancer that in aggregate encompass many of the varied aspects of the prostate cancer disease spectrum seen clinically. Using these models, we focused on the erbB-PI3K-AKT axis as a paradigm of growth factor-receptor tyrosine kinase (RTK) signaling, and the androgen-AR axis, as well as the compensatory cross-talks within and across the pathways, to study the effects of combinatoric targeting of specific nodes in these signaling pathways. Chapter 1 provides background, pre-clinical and clinical context, and translational relevance of the studies presented in this thesis. Our research work is divided into two broad areas, namely the AR negative prostate cancer cells that include both drug-sensitive and drug-resistant models (Chapter 2), and the AR positive prostate cancer cells. These are characterized by a range of molecular signatures, including changes in AR/AR-V7 expression, functional PTEN status, wild-type (wt) or mutant p53 background, and altered underlying sensitivities to androgen receptor axis targeted (ARAT) agents (Chapter 3). The present work adds to the significant body of literature in this area of study and highlights the potential relevance of combinatoric targeting across a range of underlying molecular lesions that define the different phenotypes of prostate cancer.
    • What's the Buzz? 2020

      University of Maryland, Baltimore. School of Medicine, 2020
    • Respiratory protection safety culture beliefs among healthcare workers

      Hines, Stella E.; Oliver, Marc; Gucer, Patricia; Frisch, Melissa; Hogan, Regina; Roth, Tracy; Chang, James, C.I.H.; McDiarmid, Melissa (2019-10-30)
    • Effective Collaboration Towards Positive Perioperative Outcomes for the Cardiac Surgery Patient: A Perioperative Services - Cardiac Surgery Performance Innovation Project

      Perry, Mary; Fortuno, Maridulce Belen (2020)
      Nurses in the University of Maryland Medical Center (UMMC) Procedure Readiness Evaluation and Preparation (PREP) Center care for complex patients and support multiple surgical specialties, including cardiac surgery. Workflows related to cardiac surgery, specifically identification of blood type and antibodies (“blood banding”), presented a particular challenge for the clinic, and cardiac surgery patients were not always ready for the operating room (OR) on the day of surgery. PROJECT AIMS: To provide an efficient outpatient pre-operative 30-day blood band process in the PREP Center for the outpatient adult Cardiac Surgery patient. To establish a mutually beneficial internal work flow between UMMC Perioperative Services and Cardiac Surgery staff to minimize downstream OR delays.
    • Red Herring

      Al-Hamad, Suzanne; Pietris, Nicholas; Falck, Alison (2020)
    • Trochlear Nerve palsy Due to Quadrigeminal Plate Cistern Lipoma

      Francomacaro, Sara E.; Tolbert, T.T.; Rismondo, Vivian (2020)
      Introduction: Intracranial lipomas account for <0.1% of primary brain lesions. They are most often asymptomatic incidental imaging findings, however have been reported to cause elevated ICP and seizures. Description: We present a case report of a 71 year old male with worsening binocular oblique diplopia since onset 3 years prior, found to have a right trochlear nerve palsy, without preceding head trauma. Conclusions: We report the first described case of a trochlear nerve palsy secondary to a quadrigeminal plate cistern lipoma, as confirmed by MRI imaging.
    • Risk of Subsequent Cardiovascular Events Among Medicare Beneficiaries Diagnosed with Obstructive Sleep Apnea and Treated with Continuous Positive Airway Pressure

      Ismail, M. Doyinsola; Wickwire, Emerson M.; Scharf, Steven M., 1946-; Srivastava, Mukta C.; Somers, Vivend K.; Albrecht, Jennifer S. (2020)
      Introduction: Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular disease (CVD) but it remains uncertain whether treatment with Continuous Airway Pressure (CPAP) can prevent major cardiovascular (CV) events, especially among older adults. Research Objective: To estimate the incidence of CV events among older Medicare beneficiaries, with and without pre-existing CVD, who initiated CPAP therapy following OSA diagnosis.
    • A Clinical Care Cascade for Hepatitis B Virus Vaccination in a Current Era HIV Clinic

      Deming, Meagan; Kottilil, Shyamasundaran (2020)
      Background: Hepatitis B virus (HBV) infections remain a global health issue with complications including liver cirrhosis and hepatocellular carcinoma. Individuals co-infected with Human Immunodeficiency Virus (HIV) and HBV have increased liver-related morbidity and mortality compared to those with HBV mono-infection. Vaccination is a potent intervention to prevent HBV infection, but certain critical populations including people living with HIV are less likely to achieve seroprotection after vaccination. Seroprotection (antibody to hepatitis B surface antigen [HBsAb] titer ≥10 IU/mL) was historically poor, with trial rates ranging from 34 to 88% and improving with immunologic reconstitution and viral suppression. We hypothesized that the seroprotection rates (SPR) in a clinic population of Veterans would reflect the improving immunologic status of the cohort.
    • Designing Specific Inhibitors to Target S100B in Melanoma

      Vera-Rodriguez, Darex J.; Young, Brianna; Spriggs, Shardell; Yu, Wenbo; Wilder, Paul T.; MacKerell, Alexander D., Jr.; Weber, David J., Ph.D. (2020)
      Malignant melanoma (MM) is defined as the most dangerous form of skin cancer, causing a large majority of skin cancer deaths. Previous studies demonstrate S100B as a tumor marker in MM, a protein that interacts with the tumor suppressor p53, inhibiting p53 function. With the goal of blocking this interaction, three binding sites on S100B for small molecules have been identified. However, developing drugs specific for S100B over other S100-family members remains a challenge. This project aims to identify S100B-specific small molecule inhibitors and understand the basis of their specificity over other S100 family members, specifically S100A1. A 2D-[1H,15N] NMR HSQC of S100B bound to a non-specific fragment showed multiple chemical shifts perturbations (CSPs) including residues A9, L10, F43, L40, F73, and C84. Interestingly, fewer and less pronounced CSPs were observed for a S100B-specific fragment. Site-Identified Ligand Competitive Saturation (SILCS) molecular dynamics (MD) simulations were performed to determine potential S100B binding sites that could explain the CSPs. Results show a strong hydrophobic pocket at low Grid Free Energy (GFE) levels comprised by the residues that showed CSPs for compounds that bind S100B. FDA-approved compounds were tested using SILCS-Monte Carlo (MC) to determine ligand binding poses at this pocket. Specific compounds were targeted with strong hydrophobic interactions and hydrogen bonds at low Ligand GFE (GFE). These data provide important information relevant to developing S100B-specific drugs to treat MM.
    • A Pediatric Case of Tolosa-Hunt Syndrome

      Rajjoub, Raneem D.; Aouchiche, Rachid (2020)
      Tolosa-Hunt syndrome (THS) is a rare condition characterized by episodic, painful ophthalmoplegia secondary to idiopathic inflammation of the cavernous sinus, orbital apex, or superior orbital fissure, resulting in paralysis of the third, fourth, and/or sixth cranial nerves. The incidence of THS in the United States is one case per million people annually, with a mean onset of 38-41 +/- 14-16 years. Only 18 pediatric cases have been reported in the literature and there remains controversy regarding diagnostic approach and treatment strategies in children. We aim to offer an additional successful therapeutic approach.
    • Idiopathic Intracranial Hypertension Secondary to Uremia

      Mohammed, Isa; Tran, Sang; Mathews, Michaela K. (2020)
      Idiopathic intracranial hypertension (IIH) commonly occurs in obese women of childbearing age. We report a rare case of IIH in a young patient, due to uremia in the setting of a failing kidney transplant
    • Evaluation of Surgical Site Infections after Change in Surgical Prophylaxis in Ventricular Assist Device Patients

      Min, Emily A.; Adediran, Timileyan; Thom, Kerri A.; Heil, Emily L. (2020)
      Background: Current guidelines for antimicrobial surgical prophylaxis in ventricular assist device (VAD) patients recommend single-agent cefazolin for either single dose or <24 hr continuation. In the clinical setting, prophylaxis choices for VAD patients historically included broader spectrum agents due to high morbidity and mortality associated with VAD infections. At the University of Maryland, antibiotic choice for surgical prophylaxis in VAD patients historically included broad gram-positive and gram-negative (including Pseudomonas) coverage, often vancomycin/piperacillin-tazobactam, for prolonged periods – increasing risk of antimicrobial resistance. In Oct. 2013, UMMC established standardized prophylaxis protocol for VAD patients: vancomycin + ceftriaxone for 72 hrs. Objective: To evaluate rate of surgical site infection (SSI) in VAD patients after implementation of this protocol
    • Modulation of Pathophysiological Processes of Autoimmune Arthritis by Indole-3-Acetic acid and Indole-3-Aldehyde

      Langan, David; Meka, Rakeshchandra R.; Moudgil, Kamal (2020-03)
      Rheumatoid arthritis (RA) afflicts 0.5-1% of US adults, making it one of most common autoimmune diseases. Clinical RA is characterized by swelling of the joints of both extremities. Environmental factors, including diet and microbiome dysbiosis, are disease-modifying factors for RA. Indole-3-acetic acid (I3AA) and indole-3-aldehyde (IAld) are derived from both the diet and gut microbiota. We hypothesized that I3AA and IAld, ligands for the aryl hydrocarbon receptor (AhR), regulate critical AhR-dependent arthritisrelated processes, namely production of pro-inflammatory cytokines, angiogenesis (new blood vessel formation), and osteoclastogenesis (bone resorption). We tested this using in vitro models of these 3 processes. Both I3AA and IAld inhibited IL-1β and IL-6 expression (by RT-qPCR), in RAW264.7 (RAW) cells treated with M. tuberculosis H37Ra sonicate (H37Ra) or LPS compared with vehicle control. Additionally, I3AA-treated RAW cells cultured in the presence of receptor activated nuclear-factor kappa beta (RANKL) formed fewer osteoclasts along with reduced expression of tartrate-acid phosphatase (TRAP) and cathepsin-K expression (CatK) (by RTqPCR), compared to vehicle-treated cells; whereas, IAld-treated cells formed more osteoclast along with more TRAP and CatK expression. Human umbilical vein endothelial cell (HUVEC) tube formation (Matrigel assay), indicative of angiogenesis, was inhibited by I3AA, while IAld had minimal or no effect. These preliminary results suggest that I3AA and IAld are capable of modulating key RA-disease processes. We plan to examine the effect of AhR inhibitors on these processes, and to assess whether I3AA and/or IAld can confer protection against arthritis in a rat model of RA.
    • Neuraminidase-1 Desialylates the MUC1 Ectodomain to Release a Decoy Receptor that Protects against Lethal Pseudomonas aeruginosa Lung Infection

      Lillehoj, Erik P.; Guang, Wei; Hyun, Sang Won; and others (2020)
      Background: Pseudomonas aeruginosa (Pa) is a major opportunistic pathogen of human airways, but the host response to infection is incompletely understood. Epithelial cells lining the airways express numerous surface receptors that recognize infectious agents such as Pa. One such receptor, MUC1, recognizes Pa flagellin, the major structural protein of the bacterial flagellum. MUC1 consists of an NH2-terminal, highly O-glycosylated ectodomain (MUC1-ED) attached to the cell surface through a membrane-spanning domain. MUC1-ED is proteolytically processed and shed from the epithelial cell surface following cleavage at a juxtamembranous Gly-Ser peptide bond. We previously demonstrated that stimulation of human airway epithelial cells with Pa flagellin increased MUC1-ED shedding in vitro (Lillehoj et al., J. Biol. Chem. 290:18316, 2015). Using an intact, physiologically relevant murine model of Pa pneumonia, here we asked whether Pa and its flagellin might also stimulate NEU1-dependent MUC1-ED desialylation in vivo to release a hyperadhesive decoy receptor that provides a novel, protective host response to Pa lung infection. Results: Intranasal administration of e5.0x103 colony forming units of Pa strain K (PAK) to BALB/c mice increased MUC1-ED shedding into the bronchoalveolar compartment. MUC1-ED levels increased as early as 12 h, peaked at 24-48 h, reaching up to a 7.8-fold increase, and decreased by 72 h. The a-type flagellin-expressing PAK strain and the b-type flagellin-expressing PAO1 strain stimulated comparable levels of MUC1-ED shedding. A flagellindeficient isogenic PAK mutant provoked dramatically reduced MUC1-ED shedding compared with the wild-type strain, and purified flagellin recapitulated the wild-type effect. In lung tissues, Pa increased MUC1-ED desialylation by peanut agglutinin lectin blotting. NEU1-selective sialidase inhibition with C9-BA-DANA, or use of a catalytically-inactive NEU1-G68V mutant, protected against Pa-induced MUC1-ED desialylation and shedding. MUC1-ED inhibition of in vitro Pa adhesion and flagellin binding to airway epithelial cells was localized to its protein backbone and not to its glycans. Finally, co-administration of Pa with human recombinant (r)MUC1-ED expressed in E. coli diminished lung and BALF bacterial burden, proinflammatory cytokine levels, and pulmonary leukostasis, and enhanced 5-day survival from 0% to 75%. Conclusions: These combined data indicate that Pa flagellin provokes NEU1-mediated airway shedding of MUC1-ED as a decoy receptor that protects against lethal Pa lung infection. Human rMUC1-ED might someday be harnessed as a therapeutic intervention to target Pa lung infections, including those associated with multi-drug resistant organisms.
    • NEU1 Sialidase Associates with the MUC1 Cytoplasmic Domain and not the MUC1 Ectodomain

      Lillehoj, Erik P.; Hyun, Sang Won; Piepenbrink, Kurt H.; Guang, Wei; Goldblum, Simeon E.
    • When a Rash and Fever Aren't Cellulitis

      Toler, Emily; Patel, Sonika; Wagner, Lee-Ann (2020)
      Extranodal NK/T cell lymphoma is an aggressive type of non-Hodgkin lymphoma that is rare in the United States. It is most common in Central and South America, and almost always associated with past EBV infection and B symptoms. While this lymphoma most commonly involves the nose and sinuses, it may involve the skin, gastrointestinal tract, or eyes.