Rodent Models Of Neuroinflammation For Alzheimer's Disease,
2015
Northwell Health
Rodent Models Of Neuroinflammation For Alzheimer's Disease, A. Nazem, R. Sankowski, M. Bacher, Y. Al-Abed
Journal Articles
Alzheimer's disease remains incurable, and the failures of current disease-modifying strategies for Alzheimer's disease could be attributed to a lack of in vivo models that recapitulate the underlying etiology of late-onset Alzheimer's disease. The etiology of late-onset Alzheimer's disease is not based on mutations related to amyloid-beta (A beta) or tau production which are currently the basis of in vivo models of Alzheimer's disease. It has recently been suggested that mechanisms like chronic neuroinflammation may occur prior to amyloid-beta and tau pathologies in late-onset Alzheimer's disease. The aim of this study is to analyze the characteristics of rodent models of …
A Selective Novel Peroxisome Proliferator-Activated Receptor ( Ppar)-Alpha Antagonist Induces Apoptosis And Inhibits Proliferation Of Cll Cells In Vitro And In Vivo,
2015
Zucker School of Medicine at Hofstra/Northwell
A Selective Novel Peroxisome Proliferator-Activated Receptor ( Ppar)-Alpha Antagonist Induces Apoptosis And Inhibits Proliferation Of Cll Cells In Vitro And In Vivo, D. Messmer, K. Lorrain, K. Stebbins, Y. Bravo, N. Stock, G. Cabrera, L. Correa, N. Chiorazzi, X. J. Yan, D. Lorrain, +4 Additional Authors
Journal Articles
Tumor-specific metabolic changes can reveal new therapeutic targets. Our findings implicate a supporting role for fatty acid metabolism in chronic lymphocytic leukemia (CLL) cell survival. Peroxisome proliferator-activated receptor (PPAR)-alpha, a major transcriptional regulator of fatty acid oxidation, was recently shown to be upregulated in CLL. To evaluate PPAR alpha as a potential therapeutic target, we developed a highly selective, potent small molecule antagonist of PPAR alpha, NXT629. NXT629 inhibited agonist-induced transcription of PPAR alpha-regulated genes, demonstrating target engagement in CLL cells. Furthermore, NXT629 induced apoptosis of CLL cells even in the presence of a protective microenvironment. To mimic the proliferative …
Tlr-9 And Il-15 Synergy Promotes The In Vitro Clonal Expansion Of Chronic Lymphocytic Leukemia B Cells,
2015
Zucker School of Medicine at Hofstra/Northwell
Tlr-9 And Il-15 Synergy Promotes The In Vitro Clonal Expansion Of Chronic Lymphocytic Leukemia B Cells, P. K. A. Mongini, R. Gupta, E. Boyle, J. Nieto, H. Lee, J. Stein, J. Bandovic, T. Stankovic, J. Barrientos, J. E. Kolitz, S. L. Allen, K. Rai, C. C. Chu, N. Chiorazzi
Journal Articles
Clinical progression of B cell chronic lymphocytic leukemia (B-CLL) reflects the clone's Ag receptor (BCR) and involves stroma-dependent B-CLL growth within lymphoid tissue. Uniformly elevated expression of TLR-9, occasional MYD88 mutations, and BCR specificity for DNA or Ags physically linked to DNA together suggest that TLR-9 signaling is important in driving B-CLL growth in patients. Nevertheless, reports of apoptosis after B-CLL exposure to CpG oligodeoxynucleotide (ODN) raised questions about a central role for TLR-9. Because normal memory B cells proliferate vigorously to ODN+IL-15, a cytokine found in stromal cells of bone marrow, lymph nodes, and spleen, we examined whether this …
Immune Dysregulation In Patients Persistently Infected With Human Papillomaviruses 6 And 11,
2015
Northwell Researcher
Immune Dysregulation In Patients Persistently Infected With Human Papillomaviruses 6 And 11, A. V. Lucs, J. A. Devoti, L. Hatam, A. Afzal, A. L. Abramson, B. M. Steinberg, V. R. Bonagura
Journal Articles
Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu …
N-Acetylcysteine Attenuates Tumor Necrosis Factor Alpha Levels In Autoimmune Inner Ear Disease Patients,
2015
Hofstra Northwell School of Medicine
N-Acetylcysteine Attenuates Tumor Necrosis Factor Alpha Levels In Autoimmune Inner Ear Disease Patients, S. Pathak, C. Stern, A. Vambutas
Journal Articles
Autoimmune inner ear disease (AIED) is a poorly understood disease marked by bilateral, rapidly progressive hearing loss triggered by unknown stimuli, which is corticosteroid responsive in 60 % of patients. Although the mechanism of the disease is not precisely understood, a complex interaction of cytokines is believed to contribute toward the inflammatory disease process and hearing loss. Previously, we showed the role of TNF-alpha in steroid-sensitive and IL-1beta in steroid-resistant immune-mediated hearing loss. N-Acetylcysteine (NAC), a broad spectrum antioxidant, has been effective in other autoimmune disorders. Other studies have shown NAC to have a protective adjunct role in human idiopathic …
Poly(I:C) Induces Controlled Release Of Il-36gamma From Keratinocytes In The Absence Of Cell Death,
2015
Northwell Researcher
Poly(I:C) Induces Controlled Release Of Il-36gamma From Keratinocytes In The Absence Of Cell Death, A. A. Rana, A. V. Lucs, J. Devoti, L. Blanc, J. Papoin, R. Wu, C. J. Papayannakos, A. Abramson, V. R. Bonagura, B. M. Steinberg
Journal Articles
The epithelium is part of an integrated immune system where cytokines, toll-like receptors and their ligands, and extracellular vesicles play a crucial role in initiating an innate immune response. IL-36gamma is a pro-inflammatory member of the IL-1 family that is mainly expressed by epithelial cells, but regulation of its expression and release are only beginning to be understood. Previous studies reported that IL-36gamma is abundant in recurrent respiratory papillomatosis, a rare but devastating disease caused by human papillomaviruses (HPV) types 6 and 11, in which papillomas recurrently grow in and block the airway. Despite the overexpression of IL-36gamma, papilloma tissues …
Giant Cell Tumor Of The Larynx Treated By Surgery And Adjuvant Denosumab: Case Report And Review Of The Literature,
2015
Northwell Health
Giant Cell Tumor Of The Larynx Treated By Surgery And Adjuvant Denosumab: Case Report And Review Of The Literature, A. E. Yancoskie, D. K. Frank, J. E. Fantasia, S. Savona, N. Eiseler, I. Reder, L. B. Kahn
Journal Articles
Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been reported in the literature. We report a case of GCTL in a 46 year-old male presenting clinical, radiographic, histological and therapeutic features. Previously reported cases are also reviewed.
Cholinergic Anti-Inflammatory Pathway Activity In Dialysis Patients: A Role For Neuroimmunomodulation?,
2015
Zucker School of Medicine at Hofstra/Northwell
Cholinergic Anti-Inflammatory Pathway Activity In Dialysis Patients: A Role For Neuroimmunomodulation?, M. Hilderman, A. R. Qureshi, Y. Al-Abed, F. Abtahi, K. Lindecrantz, B. Anderstam, A. Bruchfeld
Journal Articles
BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the alpha-7-nicotinic acetylcholine receptor (alpha7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients. METHODS: Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. …
Genome-Wide Association Study Of Late-Onset Myasthenia Gravis: Confirmation Of Tnfrsf11a, And Identification Of Zbtb10 And Three Distinct Hla Associations,
2015
Zucker School of Medicine at Hofstra/Northwell
Genome-Wide Association Study Of Late-Onset Myasthenia Gravis: Confirmation Of Tnfrsf11a, And Identification Of Zbtb10 And Three Distinct Hla Associations, M. F. Seldin, O. K. Alkhairy, A. T. Lee, J. A. Lamb, J. Sussman, R. Pirskanen-Matell, F. Piehl, J. J. Verschuuren, P. K. Gregersen, L. Hammarstrom, +9 Additional Authors
Journal Articles
To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million SNPs in 532 LOMG cases (anti-acetylcholine receptor (AChR) antibody positive, onset age >/=50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations [rs4574025, P = 3.9x10-07, odds ratio (OR) = 1.42] and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9x10-10, OR = 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5x10-06, OR =1.62) encoding the PTPN22 R620W variant noted in early-onset MG (EOMG) and other autoimmune …
Genome-Wide Meta-Analysis In Alopecia Areata Resolves Hla Associations And Reveals Two New Susceptibility Loci,
2015
Zucker School of Medicine at Hofstra/Northwell
Genome-Wide Meta-Analysis In Alopecia Areata Resolves Hla Associations And Reveals Two New Susceptibility Loci, R. C. Betz, L. Petukhova, S. Ripke, H. Huang, A. Menelaou, S. Redler, A. Lee, P. K. Gregersen, A. M. Christiano, +23 Additional Authors
Journal Articles
Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a …
International Genome-Wide Meta-Analysis Identifies New Primary Biliary Cirrhosis Risk Loci And Targetable Pathogenic Pathways,
2015
Zucker School of Medicine at Hofstra/Northwell
International Genome-Wide Meta-Analysis Identifies New Primary Biliary Cirrhosis Risk Loci And Targetable Pathogenic Pathways, H. J. Cordell, Y. Han, G. F. Mells, Y. Li, G. M. Hirschfield, C. S. Greene, G. Xie, B. D. Juran, K. A. Siminovitch, P. Gregersen, +14 Additional Authors
Journal Articles
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.
A Proteinuria Cut-Off Level Of 0.7 G/Day After 12 Months Of Treatment Best Predicts Long-Term Renal Outcome In Lupus Nephritis: Data From The Maintain Nephritis Trial,
2015
Zucker School of Medicine at Hofstra/Northwell
A Proteinuria Cut-Off Level Of 0.7 G/Day After 12 Months Of Treatment Best Predicts Long-Term Renal Outcome In Lupus Nephritis: Data From The Maintain Nephritis Trial, F. Tamirou, B. R. Lauwerys, M. Dall'era, M. Mackay, B. Rovin, R. Cervera, F. A. Houssiau, D. Abramowicz, L. De Bruxelles, R. Westhovens, +35 Additional Authors
Journal Articles
BACKGROUND: Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). METHODS: Long-term (at least 7 years) renal function data were available for 90 patients randomised …
Sustaining The Rheumatology Research Enterprise,
2015
Zucker School of Medicine at Hofstra/Northwell
Sustaining The Rheumatology Research Enterprise, A. Davidson, D. Polsky
Journal Articles
No abstract provided.
Tyk2 Protein-Coding Variants Protect Against Rheumatoid Arthritis And Autoimmunity, With No Evidence Of Major Pleiotropic Effects On Non-Autoimmune Complex Traits,
2015
Zucker School of Medicine at Hofstra/Northwell
Tyk2 Protein-Coding Variants Protect Against Rheumatoid Arthritis And Autoimmunity, With No Evidence Of Major Pleiotropic Effects On Non-Autoimmune Complex Traits, D. Diogo, L. Bastarache, K. P. Liao, R. R. Graham, R. S. Fulton, J. D. Greenberg, S. Eyre, A. Lee, P. K. Gregersen, R. M. Plenge, +44 Additional Authors
Journal Articles
Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to …
Widespread Non-Additive And Interaction Effects Within Hla Loci Modulate The Risk Of Autoimmune Diseases,
2015
Zucker School of Medicine at Hofstra/Northwell
Widespread Non-Additive And Interaction Effects Within Hla Loci Modulate The Risk Of Autoimmune Diseases, T. Lencz, A. J. Deutsch, B. Han, X. Hu, Y. Okada, S. Eyre, M. Knapp, A. Zhernakova, P. K. Gregersen, S. Raychaudhuri, +27 Additional Authors
Journal Articles
Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (ncases = 5,337), type 1 diabetes (T1D; ncases = 5,567), psoriasis vulgaris (ncases = 3,089), idiopathic achalasia (ncases = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, …
Pioglitazone In Early Parkinson's Disease: A Phase 2, Multicentre, Double-Blind, Randomised Trial,
2015
Hofstra Northwell School of Medicine
Pioglitazone In Early Parkinson's Disease: A Phase 2, Multicentre, Double-Blind, Randomised Trial, T. Simuni, K. Kieburtz, B. Tilley, J. J. Elm, B. Ravina, D. Babcock, M. Emborg, Andrew Feigin, R. Zweig, Parkinson Ninds Exploratory Trials, +38 Additinal Authoris
Journal Articles
Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with …
Immunological Function Of Blimp-1 In Dendritic Cells And Relevance To Autoimmune Diseases,
2015
Zucker School of Medicine at Hofstra/Northwell
Immunological Function Of Blimp-1 In Dendritic Cells And Relevance To Autoimmune Diseases, S. J. Kim
Journal Articles
Previous studies have identified the immunological functions of transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) in various adaptive immune cell types such as T and B lymphocytes. More recently, it has been shown that Blimp-1 extends its functional roles to dendritic cells (DCs) and macrophages, two cell types belonging to the innate immune system. The protein acts as a direct and indirect regulator of target genes by recruiting chromatin modification factors and by regulating microRNA expression, respectively. In DCs, Blimp-1 has been identified as one of the components involved in antigen presentation. Genome-wide association studies identified polymorphisms associated with multiple …
A Stationary Wavelet Entropy-Based Clustering Approach Accurately Predicts Gene Expression,
2015
Zucker School of Medicine at Hofstra/Northwell
A Stationary Wavelet Entropy-Based Clustering Approach Accurately Predicts Gene Expression, N. Nguyen, A. Vo, I. Choi, K. J. Won
Journal Articles
Studying epigenetic landscapes is important to understand the condition for gene regulation. Clustering is a useful approach to study epigenetic landscapes by grouping genes based on their epigenetic conditions. However, classical clustering approaches that often use a representative value of the signals in a fixed-sized window do not fully use the information written in the epigenetic landscapes. Clustering approaches to maximize the information of the epigenetic signals are necessary for better understanding gene regulatory environments. For effective clustering of multidimensional epigenetic signals, we developed a method called Dewer, which uses the entropy of stationary wavelet of epigenetic signals inside enriched …
Studies On Ageing And The Severity Of Radiographic Joint Damage In Rheumatoid Arthritis,
2015
Zucker School of Medicine at Hofstra/Northwell
Studies On Ageing And The Severity Of Radiographic Joint Damage In Rheumatoid Arthritis, L. Mangnus, H. W. Van Steenbergen, E. Lindqvist, E. Brouwer, M. Reijnierse, T. W. Huizinga, P. K. Gregersen, E. Berglin, S. Rantapaa-Dahlqvist, A. H. Van Der Helm-Van Mil, +1 Additional Author
Journal Articles
INTRODUCTION: The western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study. METHOD: 1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umea, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; …
Child And Adolescent Psychiatrists' Reported Monitoring Behaviors For Second-Generation Antipsychotics,
2015
Hofstra Northwell School of Medicine
Child And Adolescent Psychiatrists' Reported Monitoring Behaviors For Second-Generation Antipsychotics, A. M. Rodday, S. K. Parsons, C. Mankiw, C. U. Correll, A. S. Robb, B. T. Zima, T. S. Saunders, L. K. Leslie
Journal Articles
Objective: The number of children and adolescents (hereafter referred to as "children") who have been prescribed second-generation antipsychotics (SGAs) has increased over the last decade, but little is known about monitoring practices in pediatric patients who are vulnerable to adverse effects. We examined factors associated with psychiatrists' self-reported monitoring of children who were prescribed SGAs. Methods: A survey was mailed to a national, randomly selected sample of 1600 child and adolescent psychiatrists from the American Medical Association mailing list. Using logistic regression, we tested whether psychiatrist characteristics, attitudes, and practice characteristics were associated with monitoring (baseline and/or periodic) the following: …
