Structural Determination Of The Broadly Reactive Anti-Ighv1-69 Anti-Idiotypic Antibody G6 And Its Idiotope, 2017 Harvard Medical School
Structural Determination Of The Broadly Reactive Anti-Ighv1-69 Anti-Idiotypic Antibody G6 And Its Idiotope, Yuval Avnir, Kristina L. Prachanronarong, Shurong Hou, Brendan J. Hilbert, Markus-Frederik Bohn, Timothy F. Kowalik, Robert W. Finberg, Jennifer P. Wang, Nese Kurt Yilmaz, Celia A. Schiffer, Wayne A. Marasco
Schiffer Lab Publications
The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 ...
Comparing The Effectiveness Of Alternative And Prescription Antibiotics Against Gram-Positive Bacteria, Rachel Jenkins, Roan Dickenson, Sam Turnbull, Marcela Torres
The rapid emergence of antibiotic-resistant bacteria is a global public health concern that threatens the efficacy of antibiotic drugs. We found that natural remedies, specifically coconut oil, honey and cinnamon essential oil, have the potential to be used as a clinical alternative to treat antibiotic-resistant infections. In this experiment, we performed a disk diffusion test and measured the area of inhibition of each treatment to compare the effectiveness of natural and prescription antibiotics. Cinnamon essential oil showed significantly greater antibiotic activity compared to a prescription treatment, amoxicillin. With bacterial resistance continuously expanding, more work needs to be done to determine ...
Autoethnography As An Instrument For Professional (Trans) Formation In Pharmaceutical Care Practice, 2017 Universidade Federal de Minas Gerais
Autoethnography As An Instrument For Professional (Trans) Formation In Pharmaceutical Care Practice, Daniela Álvares Machado Silva, Simone Araújo Medina Mendonça, Maureen O´Dougherty, Djenane Ramalho De Oliveira, Clarice Chemello
The Qualitative Report
The recent inclusion of pharmacists in primary healthcare in Brazil through the Family Health Support Team has encouraged them to reflect on the need to change from a professional focused on medications to one focused on individuals. This autoethnography allowed a pharmacist to confront her perspectives on clinical practice between 2014 and 2016, a period when she decided to challenge her traditional training as a pharmacist centered on medications. Using pharmaceutical care practice as the theoretical framework that prompted the profession of pharmacy to change its focus to the patient, the authors collaborated to construct a monologue that engages readers ...
Investigating A Modern Midwestern Crisis: The Economy And Opioid Overdose Death In Ohio, 2017 George Washington University
Investigating A Modern Midwestern Crisis: The Economy And Opioid Overdose Death In Ohio, Anna M. Gagliardo
Undergraduate Economic Review
This paper examines the effect of local economic factors on the amount of opioid overdose deaths across counties in Ohio. Ohio leads the nation in opioid overdose deaths. The data examined spans all 88 counties of Ohio and compares 2009 and 2013 data, relying predominantly on Ohio Department of Health and US Census American Community Survey data. Using two linear regression models, I demonstrate that there is a significant correlation between insured rates and opioid overdose deaths in 2009 as well as a significant correlation between poverty rates and opioid overdose death rates in Ohio in 2013. Additionally, I show ...
Companion Diagnostics For Breast Cancer Chemotherapeutics, 2017 University of Massachusetts Medical School
Companion Diagnostics For Breast Cancer Chemotherapeutics, Monica Tawadros, Michael Morin, Peter Gaines, Abiche H. Dewilde
UMass Center for Clinical and Translational Science Research Retreat
Chemotherapy plays a major role in breast cancer treatment. However, not every chemotherapeutics is appropriate for each cancer due to the person’s individual cancer characteristics and whether the patient has developed chemoresistance to a particular drug. In this research, the InVitro-Q is used to detect subtle differences in tumor cell proliferation post-treatment with four-breast cancer chemotherapeutics used: paclitaxel, docetaxel, nocodazole, and cytochalasin B. Our multi-well cell-based sensor that can monitor real-time biological changes in living cells, such as mass redistribution, and viscoelasticity. This system provides unique kinetic information regarding the phenotypic change in the cells post treatment. Each drug ...
B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, 2017 Seton Hall University
B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips
Seton Hall University Dissertations and Theses (ETDs)
Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory ...
Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, 2017 Seton Hall University
Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, Emi Hanawa-Romero
Seton Hall University Dissertations and Theses (ETDs)
Central nervous system (CNS) disorders are becoming a major societal problem. Examples of well-known CNS disorders are: neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer’s diseases, epilepsy/seizures, addiction, bipolar disorder, catalepsy, meningitis, migraines, attention deficit/hyperactivity disorder (ADHD), and multiple sclerosis. CNS disorders can be caused by various factors and therefore can affect ages, genders and races of all.
The population of patients with CNS disorders is increasing and a significant percentage of patients have symptoms that are not controlled by existing treatments. In addition, since CNS disorders are chronic disorder, there is no cure and ...
Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition Of Exosome And Microvesicle Release And Enhanced Efficacy Of Cancer Chemotherapy, 2017 London Metropolitan University
Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition Of Exosome And Microvesicle Release And Enhanced Efficacy Of Cancer Chemotherapy, Uchini S. Kosgodage, Rita P. Trindade, Paul R. Thompson, Jameel M. Inal, Sigrun Lange
Open Access Articles
Microvesicle (MV) release from tumour cells influences drug retention, contributing to cancer drug resistance. Strategically regulating MV release may increase drug retention within cancer cells and allow for lower doses of chemotherapeutic drugs. The contribution of exosomes to drug retention still remains unknown. Potential exosome and MV (EMV) biogenesis inhibitors, tested on human prostate cancer (PC3) cells for their capacity to inhibit EMV release, were also tested on PC3 and MCF-7 (breast cancer) cells for improving chemotherapy. Agents inhibiting EMV release most significantly, whilst maintaining cell viability, were chloramidine (Cl-amidine; 50 microM) and bisindolylmaleimide-I (10 microM). Apoptosis mediated by the ...
Nitric Oxide Bioavailability In Diabetic Cardiomyocytes: The Role Of Propofol In Superoxide Scavenging, 2017 Kent State University
Nitric Oxide Bioavailability In Diabetic Cardiomyocytes: The Role Of Propofol In Superoxide Scavenging, Kayla N. Hamdan, Spencer R. Andrei, Derek S. Damron
Undergraduate Research Symposium
Background: The reaction of NO with superoxide anion to form peroxynitrite has been implicated as a potential mechanism contributing to the limited NO bioavailability observed in diabetes. Furthermore, there is little evidence outlining the effects of intravenous anesthetic, propofol, on NO bioavailability in cardiomyocytes (CMs) isolated from diabetic mice. We hypothesized that propofol would act as a superoxide scavenger, thereby increasing NO bioavailability.
Methods: For NO, superoxide and peroxynitrite measurements, freshly isolated control and diabetic CMs were incubated in the presence or absence of propofol with NO, superoxide (DHE) or peroxynitrite (HKG) fluorescent probes. Fluorescence was measured using either fluorescence ...
Krill Oil-In-Water Emulsion Protects Against Lipopolysaccharide-Induced Proinflammatory Activation Of Macrophages In Vitro, 2017 Philipps-University Marburg
Krill Oil-In-Water Emulsion Protects Against Lipopolysaccharide-Induced Proinflammatory Activation Of Macrophages In Vitro, Gabriel A. Bonaterra, David F. Driscoll, Hans Schwarzbach, Ralf Kinscherf
Open Access Articles
BACKGROUND: Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. Concerning anti-inflammatory properties in this setting, omega-3 fatty acids of marine origin have been frequently described. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO)-in-water emulsion in human macrophages in vitro.
MATERIALS AND METHODS: Differentiated THP-1 macrophages were activated using specific ultrapure-LPS that binds only on the toll-like receptor 4 (TLR4) in order ...
Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, 2017 University of Western Ontario
Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer
Western Research Forum
Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the ...
Neurotensin Nts1 And Nts2 Receptor Agonists Produce Anxiolytic-Like Effects In The 22-Khz Ultrasonic Vocalization Model In Rats, 2017 Virginia Commonwealth University
Neurotensin Nts1 And Nts2 Receptor Agonists Produce Anxiolytic-Like Effects In The 22-Khz Ultrasonic Vocalization Model In Rats, Floyd F. Steele Iii, Shannon C. Whitehouse, Jacob S. Aday, Adam J. Prus
Neurotensin is a neuropeptide neurotransmitter that interacts with multiple neurotransmitter systems, including those regulating amygdalar function, via NTS1 and NTS2 receptors. Both receptors are expressed in the amygdala and agonists for NTS1 or NTS2 receptors have exhibited anxiolytic effects in animal models. Systemic adminstration of NTS1 receptor agonist PD149163 was recently shown to reduce footshock conditioned 22-kHz ultrasonic vocalizations in rats, suggesting that PD149163 produced an anxiolytic effect. The effects that neurotensin may have or a selective NTS2receptor agonist may have on 22-kHz vocalizations has yet to be examined. The current study evaluated ...
Three Dimensional Homology Modeling Of Organic Cation Transporter 3 To Identify Structural Elements Mediating Transporter-Substrate Interactions, 2017 Virginia Commonwealth University
Three Dimensional Homology Modeling Of Organic Cation Transporter 3 To Identify Structural Elements Mediating Transporter-Substrate Interactions, Hebing Liu
Theses and Dissertations
Organic cation transporters (OCTs) play a pivotal role in the absorption, tissue distribution, and excretion of a diverse array of substances, and currently the nature of the biochemical interactions between substrate and OCTs are unknown. Therefore, identifying which amino acid residues are critical for OCT-substrate interactions is of central importance to understanding and predicting interactions between drugs and OCTs. A three-dimensional (3-D) homology model of human OCT3 was generated using the crystal structure of a high affinity phosphate transporter from Piriformospora indica (PiPT) as template, and putative binding pocket for the prototypical hOCT3 ligand 1-methyl-4-phenylpyridinium (MPP+) was identified through docking ...
Survival Model Of Intrahepatic Cholangiocarcinoma; Sex As A Biological Variable, 2017 University of Nebraska Medical Center
Survival Model Of Intrahepatic Cholangiocarcinoma; Sex As A Biological Variable, Mary A. Phillippi, Justin L. Mott, Cody J. Wehrkamp, Ying Xie, David Oupicky, Ashley M. Mohr, Bailey A. Stringham
Hepatobiliary Cancers: Pathobiology and Translational Advances
No abstract provided.
Transferrin Receptor Targeted Delivery Of Sirna For Gene Therapy, 2017 Wayne State University
Transferrin Receptor Targeted Delivery Of Sirna For Gene Therapy, Yuran Xie
Wayne State University Dissertations
Gene therapy is thought to be a solution for various difficult to treat diseases such as cancer. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence disease related gene have been exploit in different diseases. However, lack of safe and efficient siRNA delivery systems limits the application of siRNA therapy in clinic. Transferrin receptor (TfR) is an essential transmembrane receptor involved in iron uptake. TfR universally express in most cells/ tissues but upregulated in certain cells, for example, many cancer cells and activated T cells (ATCs). To overcome the biological barriers and increase siRNA delivery efficiency, in ...
Network Inference Driven Drug Discovery, 2016 University of New Mexico School of Medicine
Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd
Biomedical Sciences ETDs
The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.
The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this ...
Targeting Drug Resistance In Chronic Myeloid Leukemia: A Dissertation, 2016 University of Massachusetts Medical School
Targeting Drug Resistance In Chronic Myeloid Leukemia: A Dissertation, Leyuan Ma
GSBS Dissertations and Theses
Inhibiting BCR-ABL kinase activity with tyrosine kinase inhibitors (TKIs) has been the frontline therapy for CML. Resistance to TKIs frequently occurs, but the mechanisms remain elusive.
First, to uncover survival pathways involved in TKI resistance in CML, I conducted a genome-wide RNAi screen in human CML cells to identify genes governing cellular sensitivity to the first generation TKI called IM (Gleevec). I identified genes converging on and activating the MEK/ERK pathway through transcriptional up-regulation of PRKCH. Combining IM with a MEK inhibitor synergistically kills TKI-resistant CML cells and CML stem cells.
Next, I performed single cell RNA-seq to compare ...
Implementation Of Universal Hplc Analysis For Counterfeit Medication: A Partnership Of Purdue University And The Kilimanjaro School Of Pharmacy, Jordyn Mccord, Michael Mavity, David Wintczak
Purdue Journal of Service-Learning and International Engagement
Jordyn McCord and Michael Mavity are 2016 graduates of both biological engineering and pharmaceutical sciences. David Wintczak is a third-year pharmacy doctoral candidate. Here, in their second article published in PJSL, they describe a weeklong study abroad course at the Kilimanjaro School of Pharmacy in Tanzania, designed to engage students in the implementation of methods for detecting counterfeit medications.
Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, 2016 CUNY Hunter College
Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph
School of Arts & Sciences Theses
(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.