Cytoplasmic Myosin-Exposed Apoptotic Cells Appear With Caspase-3 Activation And Enhance Cll Cell Viability,
2016
Northwell Health
Cytoplasmic Myosin-Exposed Apoptotic Cells Appear With Caspase-3 Activation And Enhance Cll Cell Viability, X. Cui, L. Zhang, A. R. Magli, R. Catera, X. J. Yan, D. O. Griffin, T. L. Rothstein, J. Barrientos, J. E. Kolitz, S. L. Allen, K. R. Rai, N. Chiorazzi, C. C. Chu
Journal Articles
The degree of chronic lymphocytic leukemia (CLL) B-cell antigen receptor (BCR) binding to myosin-exposed apoptotic cells (MEACs) correlates with worse patient outcomes, suggesting a link to disease activity. Therefore, we studied MEAC formation and the effects of MEAC binding on CLL cells. In cell line studies, both intrinsic (spontaneous or camptothecin-induced) and extrinsic (FasL- or anti-Fas-induced) apoptosis created a high percent of MEACs over time in a process associated with caspase-3 activation, leading to cytoplasmic myosin cleavage and trafficking to cell membranes. The involvement of common apoptosis pathways suggests that most cells can produce MEACs and indeed CLL cells themselves …
Elevated 1-Hour Plasma Glucose Levels Are Associated With Dysglycemia, Impaired Beta-Cell Function, And Insulin Sensitivity: A Pilot Study From A Real World Health Care Setting,
2016
Northwell Health
Elevated 1-Hour Plasma Glucose Levels Are Associated With Dysglycemia, Impaired Beta-Cell Function, And Insulin Sensitivity: A Pilot Study From A Real World Health Care Setting, R. Jagannathan, M. A. Sevick, H. Li, D. Fink, R. Dankner, A. Chetrit, J. Roth, M. Bergman
Journal Articles
No abstract provided.
Increased Pretreatment Serum Ifn-Beta/Alpha Ratio Predicts Non-Response To Tumour Necrosis Factor Alpha Inhibition In Rheumatoid Arthritis,
2016
Northwell Health
Increased Pretreatment Serum Ifn-Beta/Alpha Ratio Predicts Non-Response To Tumour Necrosis Factor Alpha Inhibition In Rheumatoid Arthritis, T. Wampler Muskardin, P. Vashisht, J. M. Dorschner, M. A. Jensen, B. S. Chrabot, M. Kern, J. R. Curtis, R. Furie, P. K. Gregersen, T. B. Niewold, +14 Additional Authors
Journal Articles
OBJECTIVE: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. METHODS: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The …
Cytokine-Specific Neurograms In The Sensory Vagus Nerve.,
2016
Northwell Health
Cytokine-Specific Neurograms In The Sensory Vagus Nerve., B. E. Steinberg, H. A. Silverman, M. K. Gunasekaran, T. Tsaava, E. Battinelli, A. Stiegler, C. E. Bouton, S. S. Chavan, J. J. Tracey, P. T. Huerta, +1 Additional Author
Journal Articles
The axons of the sensory, or afferent, vagus nerve transmit action potentials to the central nervous system in response to changes in the body's metabolic and physiological status. Recent advances in identifying neural circuits that regulate immune responses to infection, inflammation and injury have revealed that vagus nerve signals regulate the release of cytokines and other factors produced by macrophages. Here we record compound action potentials in the cervical vagus nerve of adult mice and reveal the specific activity that occurs following administration of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin 1β (IL-1β). Importantly, the afferent vagus neurograms …
Identification Of Iguratimod As An Inhibitor Of Macrophage Migration Inhibitory Factor (Mif) With Steroid-Sparing Potential,
2016
Zucker School of Medicine at Hofstra/Northwell
Identification Of Iguratimod As An Inhibitor Of Macrophage Migration Inhibitory Factor (Mif) With Steroid-Sparing Potential, J. Bloom, C. Metz, S. Nalawade, J. Casabar, K. Fan Cheng, M. He, B. Sherry, T. Coleman, T. Forsthuber, Y. Al-Abed
Journal Articles
No abstract provided.
Dissociation Of Metabolic And Hemodynamic Levodopa Responses In The 6-Hydroxydopamine Rat Model,
2016
Zucker School of Medicine at Hofstra/Northwell
Dissociation Of Metabolic And Hemodynamic Levodopa Responses In The 6-Hydroxydopamine Rat Model, R. P. Lerner, Z. Bimpisidis, S. Agorastos, S. Scherrer, S. L. Dewey, M. A. Cenci, D. Eidelberg
Journal Articles
No abstract provided.
Association Analysis Of Copy Numbers Of Fc-Gamma Receptor Genes For Rheumatoid Arthritis And Other Immune-Mediated Phenotypes,
2016
Zucker School of Medicine at Hofstra/Northwell
Association Analysis Of Copy Numbers Of Fc-Gamma Receptor Genes For Rheumatoid Arthritis And Other Immune-Mediated Phenotypes, L. Franke, H. El Bannoudi, D. T. Jansen, K. Kok, G. Trynka, D. Diogo, M. Swertz, K. Fransen, P. K. Gregersen, A. Zhernakova, +16 Additional Authors
Journal Articles
Segmental duplications (SDs) comprise about 5% of the human genome and are enriched for immune genes. SD loci often show copy numbers variations (CNV), which are difficult to tag with genotyping methods. CNV in the Fcgamma receptor region (FCGR) has been suggested to be associated with rheumatic diseases. The objective of this study was to delineate association of FCGR-CNV with rheumatoid arthritis (RA), coeliac disease and Inflammatory bowel disease incidence. We developed a method to accurately quantify CNV in SD loci based on the intensity values from the Immunochip platform and applied it to the FCGR locus. We determined the …
Dense Genotyping Of Immune-Related Loci In Idiopathic Inflammatory Myopathies Confirms Hla Alleles As The Strongest Genetic Risk Factor And Suggests Different Genetic Background For Major Clinical Subgroups,
2016
Zucker School of Medicine at Hofstra/Northwell
Dense Genotyping Of Immune-Related Loci In Idiopathic Inflammatory Myopathies Confirms Hla Alleles As The Strongest Genetic Risk Factor And Suggests Different Genetic Background For Major Clinical Subgroups, S. Rothwell, R. G. Cooper, I. E. Lundberg, F. W. Miller, P. K. Gregersen, J. Bowes, J. Vencovsky, K. Danko, V. Limaye, J. A. Lamb, +26 Additional Authors
Journal Articles
OBJECTIVES: The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and extramuscular manifestations such as skin rashes and interstitial lung disease. We genotyped 2566 IIM cases of Caucasian descent using the Immunochip; a custom array covering 186 established autoimmune susceptibility loci. The cohort was predominantly comprised of patients with dermatomyositis (DM, n=879), juvenile DM (JDM, n=481), polymyositis (PM, n=931) and inclusion body myositis (n=252) collected from 14 countries through the Myositis Genetics Consortium. RESULTS: The human leucocyte antigen (HLA) and PTPN22 regions reached genome-wide significance (p
Loci Associated With N-Glycosylation Of Human Igg Are Not Associated With Rheumatoid Arthritis: A Mendelian Randomisation Study,
2016
Zucker School of Medicine at Hofstra/Northwell
Loci Associated With N-Glycosylation Of Human Igg Are Not Associated With Rheumatoid Arthritis: A Mendelian Randomisation Study, A. Yarwood, S. Viatte, Y. Okada, R. Plenge, K. Yamamoto, A. Barton, D. Symmons, S. Raychaudhuri, P. Gregersen, S. Eyre, +2 Additional Authors
Journal Articles
OBJECTIVES: A recent study identified 16 genetic variants associated with N-glycosylation of human IgG. Several of the genomic regions where these single nucleotide polymorphisms (SNPs) reside have also been associated with autoimmune disease (AID) susceptibility, suggesting there may be pleiotropy (genetic sharing) between loci controlling both N-glycosylation and AIDs. We investigated this by testing variants associated with levels of IgG N-glycosylation for association with rheumatoid arthritis (RA) susceptibility using a Mendelian randomisation study, and testing a subset of these variants in a less well-powered study of treatment response and severity. METHODS: SNPs showing association with IgG N-glycosylation were analysed for …
Lower Omega-3 Fatty Acids Are Associated With The Presence Of Anti-Cyclic Citrullinated Peptide Autoantibodies In A Population At Risk For Future Rheumatoid Arthritis: A Nested Case-Control Study,
2016
Zucker School of Medicine at Hofstra/Northwell
Lower Omega-3 Fatty Acids Are Associated With The Presence Of Anti-Cyclic Citrullinated Peptide Autoantibodies In A Population At Risk For Future Rheumatoid Arthritis: A Nested Case-Control Study, R. W. Gan, K. A. Young, G. O. Zerbe, M. K. Demoruelle, M. H. Weisman, J. H. Buckner, P. K. Gregersen, T. R. Mikuls, J. R. O'Dell, J. M. Norris, +4 Additional Authors
Journal Articles
OBJECTIVE: The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. METHODS: The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to …
What Is Damaging The Kidney In Lupus Nephritis?,
2016
Zucker School of Medicine at Hofstra/Northwell
What Is Damaging The Kidney In Lupus Nephritis?, A. Davidson
Journal Articles
Despite marked improvements in the survival of patients with severe lupus nephritis over the past 50 years, the rate of complete clinical remission after immune suppression therapy is
Whole-Exome Sequencing In Relapsing Chronic Lymphocytic Leukemia: Clinical Impact Of Recurrent Rps15 Mutations,
2016
Zucker School of Medicine at Hofstra/Northwell
Whole-Exome Sequencing In Relapsing Chronic Lymphocytic Leukemia: Clinical Impact Of Recurrent Rps15 Mutations, V. Ljungstrom, D. Cortese, E. Young, T. Pandzic, L. Mansouri, K. Plevova, S. Ntoufa, P. Baliakas, N. Chiorazzi, R. Rosenquist, +24 Additional Authors
Journal Articles
Fludarabine, cyclophosphamide and rituximab (FCR) is first-line treatment for medically fit chronic lymphocytic leukemia (CLL) patients, however despite good response rates many patients eventually relapse. Whilst recent high-throughput studies have identified novel recurrent genetic lesions in adverse-prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, BIRC3) a large proportion of cases …
Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells,
2016
Rowan University
Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown
Graduate School of Biomedical Sciences Theses and Dissertations
In order for a cancer cell to thrive, it must alter its metabolism to produce the energy needed for rapid growth. Cells accomplish this by the Warburg Effect, or switching metabolism to aerobic glycolysis, where a cell can rapidly break down sugar into ATP, lactic acid and additional byproducts. Hexokinase 2, the enzyme that catalyzes the first committed step of glycolysis, may also be upregulated in cancer cells to increase glucose breakdown. Similar proteins for metabolism are found in both S. cerevisiae and mammalian cells. S. cerevisiae regulates metabolism through glucose repression, by Snf1 (mammalian homolog: AMPK) activation, which aids …
Nrf2 Pathway And The Reduction Of Oxidative Stress,
2016
University of North Dakota
Nrf2 Pathway And The Reduction Of Oxidative Stress, Stephanie Jacobs Uselman
Physician Assistant Scholarly Project Posters
Oxidative stress has been linked to cellular damage initiating disease processes such as cardiovascular disease, diabetes, and cancer. The Nuclear factor erythroid-derived 2(Nrf2) pathway (Figure 1) aids in age-related cellular decline. The purpose of this study was to define the relationship between Protandim, its activation of the Nrf2 pathway, and decline in oxidative stress and cellular damage. The literature review included journal articles obtained from PubMed, Google scholar, and Cochrane review within the past 5-10 years, and contained both animal and human studies. The methods used in the animal studies included ANOVA, the standardized t-test, and the Neuman-Keuls post-test. P<0.05 was considered statistically significant. The human study included healthy participants, both male and female, age 29-78 with or without a specific medical diagnosis. Statistical analysis was based on the standardized t-test with a value of p<0.05 considered statistically significant. Liu et al. (2009) conducted a study investigating Protandim’s ability to suppress cancer tumor formation. Tumor incidence declined by 33% and multiplicity of skin tumors by 57% with p = 0.003. Superoxide dismutase increased 35%, catalase 58%, and manganese superoxide dismutase 21%. In 2013, Reuland et al. conducted a study to determine if Protandim could activate the Nrf2 pathway and induce antioxidant enzymes, thereby protecting cardiomyocytes from apoptosis. Results indicated that treated cardiomyocytes showed increased levels of Nrf2 nuclear accumulation, activation of endogenous antioxidant enzymes, and protection against cell targeted oxidative stress (p<0.05). Quereshi et al. (2010) completed a study to delineate if Protandim decreased oxidative stress through the Nrf2 pathway. After six months of supplementation, TBARS decreased by 48% (p=.006), and plasma osteopontin decreased by 57% (p=.018). In 2005, Nelson et al. conducted a study to determine if Protandim decreased cellular damage. After 30 days of supplementation, TBARS declined by 40% (p =0.0001), at 120 days, TBARS declined by 40-54% (p =0.002), and superoxide dismutase and catalase increased by 30% and 54% respectively. The results from studies indicate that Protandim’s activation of the Nrf2 pathway increased endogenous antioxidant availability, resulting in decreased oxidative stress and age related cellular damage.
Expression Levels Of Virulence Genes In Group A Streptococci: A Response To Aerosolized Propylene Glycol,
2016
University of Central Florida
Expression Levels Of Virulence Genes In Group A Streptococci: A Response To Aerosolized Propylene Glycol, Michael S. Costello
Honors Undergraduate Theses
Electronic cigarette usage is becoming increasingly prevalent among school age children and young adults. A known bactericidal agent, propylene glycol, is often used as a carrier for nicotine, flavoring, and additional constituents of electronic cigarette juice. This study examined the relationship between propylene glycol and virulence gene expression in Streptococcus pyogenes, a respiratory tract pathogen commonly found in school-age individuals. A variety of virulence genes controlled by the three stand alone regulators mga, RofA, and Rgg/RopB were sampled in an effort to understand the pathway by which virulence is affected. The genes chosen encode C5a peptidase, fibronectin binding protein, hyaluronate …
Pcsk9 Inhibitors: A Review Of The Efficacy, Safety And Current Literature Recommendations,
2016
University of North Dakota
Pcsk9 Inhibitors: A Review Of The Efficacy, Safety And Current Literature Recommendations, Lacey L. Jandrin
Physician Assistant Scholarly Project Posters
Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality in developed counties. It is estimated that 60 million Americans have LDL-C levels > 160 mg/dl. Only about 1/3 of these patients meet treated LDL cholesterol goals of < 70 mg/dl indicating a need for greater control. High dose statins have been the mainstay in treatment of dyslipidemia, however, up to 20% of patients are statin intolerant indicating a need for secondary treatment strategies. This lead to the development of monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. PCSK9 inhibitors result in decreased destruction of the low-density lipoprotein receptor (LDL-R) which leads to an increase in the transport of LDL-C to its destruction effectively reducing LDL-C levels in the blood. The purpose of this study is to analyze the literature available on the efficacy and safety of new PCSK9 inhibitors. The results of this literature review indicated that PCSK9 inhibitors effectively lowered LDL-C by an average of approximately 50%. The evidence reviewed by this analysis indicate that 70% of patients treated with PCSK9 inhibitors met LDL-C goals. The findings also indicate that the side effects associated with this new class of medications are comparable to current side effects seen with traditional cholesterol lowering agents. The largest side effect seen in up to 10% of patients were injection site reactions and did not require discontinuation of the medication. The results of this analysis indicate that PCSK9 inhibitors may be of benefit in patients who are statin intolerant, do not meet LDL-C goals on traditional statin therapy or have familial hypercholesterolemia. Education in use of injectables, cost and insurance coverage and dosing schedule are likely to be areas of continued research and may affect use of this new class of cholesterol lowering agents.
Role Of Sulfiredoxin Interacting Proteins In Lung Cancer Development,
2016
University of Kentucky
Role Of Sulfiredoxin Interacting Proteins In Lung Cancer Development, Hedy Chawsheen
Theses and Dissertations--Toxicology and Cancer Biology
Sulfiredoxin (Srx) is an antioxidant enzyme that can be induced by oxidative stress. It promotes oncogenic phenotypes of cell proliferation, colony formation, migration, and metastasis in lung, skin and colon cancers. Srx reduces the overoxidation of 2-cysteine peroxiredoxins in cells, in addition to its role of removing glutathione modification from several proteins. In this study, I explored additional physiological functions of Srx in lung cancer through studying its interacting proteins. Protein disulfide isomerase (PDI) family members, thioredoxin domain containing protein 5 (TXNDC5) and protein disulfide isomerase family A member 6 (PDIA6), were detected to interact with Srx. Therefore, I proposed …
The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease,
2016
University of Kentucky
The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley
Theses and Dissertations--Pharmacology and Nutritional Sciences
Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …
Identification And Characterization Of Dna Repair Snf2/Swi2 Atpases In Tetrahymena Thermophila,
2016
Missouri State University
Identification And Characterization Of Dna Repair Snf2/Swi2 Atpases In Tetrahymena Thermophila, Andrew Francis Morin
Graduate Theses/Dissertations
The Snf2/Swi2 ATPases Rad5 and Rad16 have been shown to play vital roles in a number of DNA repair pathways. In both Saccharomyces cerevisiae and human cell lines, Rad5 homologs (SHPRH, HLTF) have been shown to function in DNA double strand break (DSB) repair along with pathways that repair damage after replication. The function of Rad16, unlike Rad5, has been found only in lower eukaryotes such as Saccharomyces, despite the fact that it plays an essential role in nucleotide excision repair (NER), and more specifically in the repair of silenced areas of the genome. In order to more fully understand …
Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis,
2016
Dartmouth College
Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield
Dartmouth Scholarship
Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.
