Medicine and Health Sciences Commons^™

Stages Of Chronic Kidney Disease And Soluble Transferrin Receptor (Stfr), Ferritin, Ratio, Faiza Alam Faiza Alam, Syeda Sadia Fatima, Sabeela Noor Sabeela Noor, Ahmed Bilal, Rehana Rehman

Department of Biological & Biomedical Sciences

Objective: To assess the ratio of soluble transferrin receptor to ferritin in different stages of chronic kidney disease.
Methods: This case-control study was conducted at the Aga Khan University Hospital and the Jinnah Postgraduate Medical Centre, Karachi, from January to September 2014, and comprised chronic kidney disease patients and healthy controls. Group 1 comprised controls, whereas groups 2, 3 and 4 had patients based on their mean glomerular filtration rate. SPSS 19 was used for data analysis.
Results: Of the 170 participants, 126(74.1%) were cases and 44(25.9%) were controls. The overall mean age was 55.87±3.48 years and the mean body …

Effect Of Speaker Age And Dialect On Listener Perceptions Of Personality, Brittni Elizabeth Bergstrom

Theses and Dissertations

The association between dialect and perceived personality traits has been studied for a number of years. The purpose of this study was to examine how the dialect, the gender of both the speaker and the listener, and the perceived age of the speaker affected the listeners' perception of the speaker's personality. The spontaneous speech samples were drawn from existing corpora. There were 48 speakers, 24 New Zealanders and 24 Utahns. Each dialect group was stratified into three age groups (young, middle, older), and within each age group there were an equal number of males and females. The listener group included …

Genome- And Cd4+ T-Cell Methylome-Wide Association Study Of Circulating Trimethylamine-N-Oxide In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn), Stella Aslibekyan, Marguerite R. Irvin, Bertha A. Hidalgo, Rodney T. Perry, Elias J. Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N. Hopkins, Michael A. Province, Hemant K. Tiwari, Jose M. Ordovas, Devin M. Absher, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels.

Methods and results: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans. TMAO was not associated with other plasma markers of cardiovascular disease, …

Early Postnatal Treatment Effect Of Methylphenidate On Spontaneous And Reward Alteration And Neuronal Morphology Of Hippocampus In Rats, Elizabeth Josy Paniculum, Sampath Madhyastha, Teresa Joy, Vandana Blossom, Rai Rajalakshmi, Murlimanju Bv

Manipal Journal of Medical Sciences

No abstract provided.

Genome-Wide Chromatin Accessibility, Dna Methylation And Gene Expression Analysis Of Histone Deacetylase Inhibition In Triple-Negative Breast Cancer., Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L Dinome, Dave S B Hoon, Diego M Marzese

Articles, Abstracts, and Reports

Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors. However, the genome-wide epigenetic and transcriptomic implications of HDAC inhibition are still poorly understood. Here, we provide detailed information about the …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …

The Choice Of A Constitutive Formulation For Modeling Limb Flexion-Induced Deformations And Stresses In The Human Femoropopliteal Arteries Of Different Ages, Anastasia Desyatova, Jason Mactaggart, William Poulson, Paul Deegan, Carol Lomneth, Anjali Sandip, Alexey Kamenskiy

Mechanical Engineering Faculty Publications

Open and endovascular treatments for peripheral arterial disease are notorious for high failure rates. Severe mechanical deformations experienced by the femoropopliteal artery (FPA) during limb flexion and interactions between the artery and repair materials play important roles and may contribute to poor clinical outcomes. Computational modeling can help optimize FPA repair, but these simulations heavily depend on the choice of constitutive model describing the arterial behavior. In this study finite element model of the FPA in the standing (straight) and gardening (acutely bent) postures was built using computed tomography data, longitudinal pre-stretch and biaxially determined mechanical properties. Springs and dashpots …

Cross-Talk Between Clinical And Host-Response Parameters Of Periodontitis In Smokers, Radha Nagarajan, Craig S. Miller, Dolph R. Dawson Iii, Mohanad Al-Sabbagh, Jeffrey L. Ebersole

Institute for Biomedical Informatics Faculty Publications

Background and Objective

Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host‐response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens …

The 2016 Model Of The Clinical Practice Of Emergency Medicine, Francis L. Counselman, Kavita Babu, Mary Ann Edens, Diane L. Gorgas, Cherri Hobgood, Catherine A. Marco, Eric Katz, Kevin Rodgers, Leonard A. Stallings, Michael C. Wadman

Emergency Medicine Faculty Publications

Emergency medicine (EM) has a scientifically derived and commonly accepted description of the domain of its clinical practice. That document, “The Model of the Clinical Practice of Emergency Medicine” (EM Model), was developed through the collaboration of six organizations: the American Board of Emergency Medicine (ABEM), the administrative organization for the project, the American College of Emergency Physicians (ACEP), the Council of Emergency Medicine Residency Directors (CORD), the Emergency Medicine Residents' Association (EMRA), the Residency Review Committee for Emergency Medicine (RRC-EM), and the Society for Academic Emergency Medicine (SAEM). Development of the EM Model was based on an extensive practice …

Knowledge And Trends Of Caffeine Consumption Among Medical And Non Medical Students Of Lahore Pakistan, Mubashir Ahmad, Rashk E Hinna, Ahmad Tayyab

Pakistan Journal of Neurological Sciences (PJNS)

To determine the rate of the caffeine consumption among students and to assess side effects and benefits of the caffeine among medical and non-medical students. METHODOLOGY: This cross-sectional study was included medical and non-medical students of various institutes of Lahore. The study duration was three months from May 2014 to July 2014. A predesigned structured questionnaire was used to collect data from the students, Consent was obtained on the form beforehand. RESULTS: Astonishingly 98.6%(74) of medical and 97.4%(73) of the Non-Medical students said that they consume caffeine in one form or another, the most popular caffeinated product turned out to …

Infections In Post Stroke Setting: A Study From The Neurology Section Of Aga Khan University Hospital, Karachi, Rizwana Shahid, Azra Zafar, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

Stroke is one of the commonest neurological disorders, contributing to the major burden of inpatient and outpatient neurology services. Infections after the stroke are the major factor, contributingto prolonged hospital stay and poor outcome in term of increasing morbidity and mortality. The aim of this study is to define the different types of infections in post stroke patients and their impact on the outcome of patients with stroke. METHOD: This is a descriptive, cross sectional study, that was carried out in the section of Neurology, Department of Medicine at Aga Khan University Hospital, Karachi over the span of one year. …

Endometriosis, Jessica Workman

Nursing Student Class Projects (Formerly MSN)

Many people have heard about endometriosis but not a lot is understood about the condition. Endometriosis is a condition where endometrium, tissue that lines the uterus, grows outside the uterus. This tissue can grow around the ovaries, fallopian tubes, bowels, and bladder. When this occurs, the surrounding tissue becomes inflamed, swollen and irritated which causes scarring. The resulting lesions impede the function of the organs that they surround. The inflammation and tissue damage can lead to bleeding and painful discomfort.

There is much debate over the exact cause of endometriosis and how to best treat the condition. It is also …

Pain Perception In Latino Vs. Caucasian And Male Vs. Female Patients: Is There Really A Difference?, Molly Aufiero, Holly Stankewicz, Shaila Quazi, Jeanne Jacoby, Jill Stoltzfus

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

INTRODUCTION: Pain is a common emergency department (ED) complaint. It is important to understand the differences in pain perception among different ethnic and demographic populations.

METHODS: We applied a standardized painful stimulus to Caucasian and Latino adult patients to determine whether the level of pain reported differed depending on ethnicity (N=100; 50 Caucasian [C], 50 Latino [L] patients) and gender (N=100; 59 female, 41 male). Patients had an initial pain score of 0 or 1. A blood pressure cuff was inflated 20 mm HG above the patient's systolic blood pressure and held for three minutes. Pain scores, using both a …

Microalbuminuria In Type-2 Diabetes Mellitus; The Tip Of Iceberg Of Diabetic Complications., Tauseef Ahmad, Imran Ulhaq, Minaz Mawani, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Objective: To determine the prevalence of microalbuminuria and its association with hypertension and other diabetic complications among Type-2 diabetic patients attending at Aga Khan University Hospital Karachi.

Methods: 1280 Type-2 diabetes patients who visited the outpatient department of Aga Khan University Hospital from September 2014 to August 2016 were included in the study. Microalbuminuria was diagnosed if spot urinary microalbumin excretion was confirmed to be more than 20mg/l. Hypertension was diagnosed if BP >140/90 or already on antihypertensive medications. Other demographic, clinical and laboratory data were also recorded. Results: Microalbuminuria was diagnosed in 404(31.56%) patients and among these albuminuric patients …

Vitamin-D Toxicity And Other Non-Malignant Causes Of Hypercalcemia: A Retrospective Study At A Tertiary Care Hospital In Pakistan, Muhammad Naeem Khan, Qamar Masood, Mohammad Arsalan Siddiqui, Sabahat Naz, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Background: Hypercalcemia is a common clinical problem; primary hyperparathyroidism and malignancy is commonest causes of hypercalcemia. Aetiology of hypercalcemia are changing, causes that were diseases of the past like Vitamin-D toxicity and milk alkali syndrome are observed more often. Vitamin-D deficiency is an important problem and overzealous replacement of Vitamin-D has been observed, suspected to cause toxicity.

Methods: This was a retrospective review of patients admitted at the Aga Khan University Hospital from January 2008 to December 2013 with hypercalcemia. We reviewed the electronic health records for laboratory and radiological studies, and discharge summaries to establish the cause of hypercalcemia. …

Stimulus-Selectivity Of Drug Purchase Tasks: A Preliminary Study Evaluating Alcohol And Cigarette Demand, Justin Charles Strickland, William W. Stoops

Psychology Faculty Publications

The use of drug purchase tasks to measure drug demand in human behavioral pharmacology and addiction research has proliferated in recent years. Few studies have systematically evaluated the stimulus selectivity of drug purchase tasks to demonstrate that demand metrics are specific to valuation of or demand for the commodity under study. Stimulus selectivity is broadly defined for this purpose as a condition under which a specific stimulus input or target (e.g., alcohol, cigarettes) is the primary determinant of behavior (e.g., demand). The overall goal of the present study was to evaluate the stimulus selectivity of drug purchase tasks. Participants were …

Swainsonine Biosynthesis Genes In Diverse Symbiotic And Pathogenic Fungi, Daniel Cook, Bruno G. G. Donzelli, Rebecca Creamer, Deana L. Baucom, Dale R. Gardner, Juan Pan, Neil Moore, Stuart B. Krasnoff, Jerzy W. Jaromczyk, Christopher L. Schardl

Plant Pathology Faculty Publications

Swainsonine—a cytotoxic fungal alkaloid and a potential cancer therapy drug—is produced by the insect pathogen and plant symbiont Metarhizium robertsii, the clover pathogen Slafractonia leguminicola, locoweed symbionts belonging to Alternaria sect. Undifilum, and a recently discovered morning glory symbiont belonging to order Chaetothyriales. Genome sequence analyses revealed that these fungi share orthologous gene clusters, designated “SWN,” which included a multifunctional swnKgene comprising predicted adenylylation and acyltransferase domains with their associated thiolation domains, a β-ketoacyl synthase domain, and two reductase domains. The role of swnK was demonstrated by inactivating it in M. robertsii through homologous …

Salivary And Serum Adiponectin And C-Reactive Protein Levels In Acute Myocardial Infarction Related To Body Mass Index And Oral Health, Jeffrey L. Ebersole, Richard J. Kryscio, C. Campbell, D. F. Kinane, J. Mcdevitt, N. Christodoulides, P. N. Floriano, Craig S. Miller

Oral Health Practice Faculty Publications

Background and Objective

Adiponectin is produced by adipose cells and is considered an anti‐inflammatory molecule. In contrast, C‐reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk.

Material and Methods

This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be …

Comparative Standardization Study For Determination Of Reserpine In Rauwolfia Serpentina Homoeopathic Mother Tinctures Manufactured By Different Pharmaceutical Industries Using Hptlc As A Check For Quality Control, Binit Dwivedi, Manoj Kumar, Anil Khurana, Bhopal Arya, Echur Sundaram, Raj Manchanda

Indian Journal of Research in Homoeopathy

Background: Rauwolfia serpentina (L.) Benth. ex Kurz (Apocynaceae) (Indian snakeroot), popularly known as Sarpagandha (Sanskrit), is used for the treatment of insanity, fever, snake bites, anxiety and in neuropsychiatric conditions. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines (amongst other monoamine neurotransmitters) from peripheral sympathetic nerve endings which are normally involved in controlling heart rate, force of cardiac contraction and peripheral vascular resistance. Objective: Comparative study of Reserpine content in R. serpentina homoeopathic mother tinctures manufactured by different pharmaceutical industries and in-house mother tinctures applying high-performance thin-layer chromatography investigative techniques to facilitate the use …

World Integrated Medicine Forum On The Regulation Of Homoeopathic Medicinal Products: National And Global Strategies, Harleen Kaur, Anupriya Chaudhary, Anil Khurana, Todd Hoover, Robbert Van Haselen, Raj Manchanda

Indian Journal of Research in Homoeopathy

The first World Integrated Medicine Forum on the regulation of homoeopathic medicinal products included 50 delegates from 25 countries to discuss the current state of regulation of homoeopathic medicinal products (HMPs). The stakeholders in attendance included government officials, manufacturers, pharmacopoeia organisations, pharmacists, and healthcare providers worldwide. The Minister of Ayurveda, Yoga, Unani, Siddha and Homoeopathy from India, who is likely the only high ranking national official in the world specifically dedicated to oversight of traditional medicines including Homoeopathy, was the keynote speaker for the meeting. The core presentations delivered information on the country-to-country variance in regulatory requirements for homoeopathic medicine …

Incorporating Place And Space: A Hierarchical Spatial Approach To Exploring Preventable Congestive Heart Failure Hospitalizations In New York City, Rachael Weiss Riley

Dissertations and Theses

Background: Faced with rising medical care costs, increasing prevalence, and widening health disparities, preventing congestive heart failure (CHF) hospitalizations is a central public health concern. Despite evidence of geographical clustering in preventable CHF admissions, there is a lack of research designed to examine spatial patterning of CHF and the local area neighborhood determinants that contribute to this variability. This study sought to assess and evaluate the importance of both space and place in analyzing preventable CHF hospitalizations and readmissions by applying appropriate statistical techniques, clarifying the assumption inherent in each method, and interpreting the findings within the context of existing …

The Role Of Socioeconomic Context In The Association Between Educational Attainment And Morbidity And Mortality, Jennifer Brite

Dissertations and Theses

Although the association between educational attainment and health is one of the most studied in the social science, little is known about the role of social and economic context. Fundamental Cause Theory suggests that the education-health gradient will be weakest in contexts where the better educated are unable to leverage their resources to achieve better health. This dissertation tests several different factors that may moderate the association between educational attainment and morbidity and mortality: 1. Demographic characteristics, including race, immigration status, and gender, 2. Status consistency (defined as education equivalent to that required for current occupation), 3. Unemployment rates at …

How Much Are Ecuadorians Willing To Pay To Reduce Maternal Mortality? Results From A Pilot Study On Contingent Valuation, Maria-Isabel Roldos, Phaedra Corso, Justin Engel

Publications and Research

Context:

There is an established association between the provision of health care services and maternal mortality. In Ecuador, little is known if the societal value is greater than the resources expended in preventive medicine.

Aims:

The purpose of this research is to investigate Ecuadorians’ willingness to pay to prevent maternal death and disabilities due to complications of care during childbirth in the context of universal coverage.

Methods and Materials:

The study elicited a “contingent” market on morbidity and mortality outcomes, specific to Ecuador’s epidemiologic profiles between a hypothetical market that included a 50% reduction in the risk of maternal mortality …

Cime Newsletter : June 2017, Cime

Centre for Innovation in Medical Education (CIME) Archives

- A Milestone in Simulation Embracing Flip Style Teaching

- Regional Simulation Experts spend a day at CIME

- Rapid Response Team Simulation Video

- CIME on the intranet NOW

- Introducing our latest acquisition: Mr Talha Ahmed

- Orthopaedic Review Course

- Moulage

- Another first: Neuro Simulation Workshop Complete IT integration of the Dental Lab

- Fundamental Critical Care Support

- Provider Course

- A Surgical Skills workshop

- A Spinal Trauma Workshop

- IED and CIME

Immune Checkpoint Inhibition And The Prevalence Of Autoimmune Disorders Among Patients With Lung And Renal Cancer, Sherif M. El-Refai

Pharmaceutical Sciences Faculty Publications

PURPOSE: Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation. We sought to identify, among patients with lung and renal cancer, how many harbor a comorbid autoimmune condition and may be at risk of worsening their condition while on immune checkpoint inhibitors such as nivolumab and pembrolizumab.

METHODS: An administrative health care claims database, Truven MarketScan, was used to identify patients diagnosed with lung and renal cancer from 2010 to 2013. We assessed patients …

Comparison Of Online 6 Degree-Of-Freedom Image Registration Of Varian Truebeam Cone-Beam Ct And Brainlab Exactrac X-Ray For Intracranial Radiosurgery., Jun Li, Wenyin Shi, David W. Andrews, Maria Werner-Wasik, Bo Lu, Yan Yu, Adam Dicker Md, Phd, Haisong Lui

Department of Radiation Oncology Faculty Papers

PURPOSE: The study was aimed to compare online 6 degree-of-freedom image registrations of TrueBeam cone-beam computed tomography and BrainLab ExacTrac X-ray imaging systems for intracranial radiosurgery.

METHODS: Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (version 2.5), which is integrated with a BrainLab ExacTrac imaging system (version 6.1.1). The phantom study was based on a Rando head phantom and was designed to evaluate isocenter location dependence of the image registrations. Ten isocenters at various locations representing clinical treatment sites were selected in the phantom. Cone-beam computed tomography and ExacTrac X-ray images were taken when the …

Lysozyme Association With Circulating Rna, Extracellular Vesicles, And Chronic Stress, Sarah K. Abey, Yuana Yuana, Paule V. Joseph, Natnael D. Kenea, Nicolaas H. Fourie, Lee Anne B. Sherwin, Gregory E. Gonye, Paul A. Smyser, Erin S. Stempinski, Christina M. Boulineaux, Kristen R. Weaver-Toedtman Phd, Acnp, Anp, Christopher K.E. Bleck, Wendy A. Henderson

Publications

Background Stress has demonstrated effects on inflammation though underlying cell-cell communication mechanisms remain unclear. We hypothesize that circulating RNAs and extracellular vesicles (EVs) in patients with chronic stress contain signals with functional roles in cell repair. Methods Blood transcriptome from patients with Irritable Bowel Syndrome versus controls were compared to identify signaling pathways and effectors. Plasma EVs were isolated (size-exclusion chromatography) and characterized for effectors’ presence (immunogold labelling-electron microscopy). Based on transcriptome pathways and EV-labelling, lysozyme's effects on cell migration were tested in human colon epithelial CRL-1790 cells and compared to the effects of CXCL12, a migration inducer (wound assay). …

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

The Quest For Sustained Multiple Morbidity Reduction In Very Low-Birth-Weight Infants: The Antifragility Project., Joseph Kaempf, N M Schmidt, S Rogers, C Novack, M Friant, L Wang, N Tipping

Articles, Abstracts, and Reports

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities?

STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always …

Identification Of A Nucleoside Analog Active Against Adenosine Kinase-Expressing Plasma Cell Malignancies, Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J. Barelli, Michelle A. Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H. Shoemaker, J. David Warren, Olivier Elemento, Kenneth M. Kaye, Ethel Cesarman

Pharmacy Faculty Articles and Research

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we …