Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway.,
2016
University of Colorado, Denver
Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik
Journal Articles: Biochemistry & Molecular Biology
Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …
Overexpression Of Pd2 Leads To Increased Tumorigenicity And Metastasis In Pancreatic Ductal Adenocarcinoma.,
2016
University of Nebraska Medical Center
Overexpression Of Pd2 Leads To Increased Tumorigenicity And Metastasis In Pancreatic Ductal Adenocarcinoma., Arokia Priyanka Vaz, Shonali Deb, Satyanarayana Rachagani, Parama Dey, Sakthivel Muniyan, Imayavaramban Lakshmanan, Saswati Karmakar, Lynette M. Smith, Sonny L. Johansson, Subodh M. Lele, M Ouellette, Moorthy P. Ponnusamy, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
Pancreatic differentiation 2 (PD2), an important subunit of the human PAF complex, was identified after differential screening analysis of 19q13 amplicon, and its overexpression induces oncogenic transformation of NIH3T3 cells, hence raising the possibility of a role for PD2 in tumorigenesis and metastasis. To test this hypothesis, we analyzed here the functional role and clinical significance of PD2 in pancreatic ductal adenocarcinoma (PDAC) and its pathogenesis. Using immunohistochemical analysis, we found that PD2 is detected in the acini but not in the ducts in the normal pancreas. In human PDAC specimens, PD2 was instead primarily detected in the ducts (12/48 …
The Frequency And Outcome Of Lupus Nephritis: Results From An International Inception Cohort Study,
2016
Zucker School of Medicine at Hofstra/Northwell
The Frequency And Outcome Of Lupus Nephritis: Results From An International Inception Cohort Study, J. G. Hanly, A. G. O'Keeffe, L. Su, M. B. Urowitz, J. Romero-Diaz, C. Gordon, S. C. Bae, E. M. Ginzler, C. Aranow, V. Farewell, +35 Additional Authors
Journal Articles
OBJECTIVE: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort (
Analysis Of Igm Antibody Production And Repertoire In A Mouse Model Of Sjogren's Syndrome,
2016
Northwell Health
Analysis Of Igm Antibody Production And Repertoire In A Mouse Model Of Sjogren's Syndrome, J. M. Kramer, N. E. Holodick, T. C. Vizconde, I. Raman, M. Yan, Q. Z. Li, D. P. Gaile, T. L. Rothstein
Journal Articles
This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjogren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjogren's syndrome mouse model (Id3-/-). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells. We single-cell sorted B cells from the spleen, cervical lymph nodes, and submandibular gland tissue from Sjogren's syndrome mice and sequenced immunoglobulin M heavy-chain variable regions. Finally, autoantigen arrays were performed using immunoglobulin M derived from sera, cervical lymph …
Btk Inhibition Results In Impaired Cxcr4 Chemokine Receptor Surface Expression, Signaling And Function In Chronic Lymphocytic Leukemia,
2016
Northwell Health
Btk Inhibition Results In Impaired Cxcr4 Chemokine Receptor Surface Expression, Signaling And Function In Chronic Lymphocytic Leukemia, S. S. Chen, B. Y. Chang, S. Chang, T. Tong, S. Ham, B. Sherry, J. A. Burger, K. R. Rai, N. Chiorazzi
Journal Articles
Bruton's tyrosine kinase (BTK) is involved in the regulation of B-cell growth, migration and adhesion. The importance of BTK in cell trafficking is emphasized by the clonal contraction proceeded by lymphocytosis typical for the enzyme inhibitor, ibrutinib, in B-cell malignancies, including chronic lymphocytic leukemia (CLL). Here, we investigated BTK regulation of leukemic B-cell trafficking in a mouse model of aggressive TCL1 CLL-like disease. Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors. Decreased smCXCR4 levels resulted from blocking receptor signal transduction, which in turn aborted cycling from and to the …
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 …
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 …
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 …
