Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice,
2014
Northwell Health
Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice, G. Liu, X. B. Ye, E. J. Miller, S. F. Liu
Journal Articles
Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-kappa B-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-kappa B mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-kappa B pathway activated the activator protein (AP)-1 pathway (NF-kappa B-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-kappa B. The NF-kappa B-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) …
A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production,
2014
Northwell Health
A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production, H. Kaku, K. F. Cheng, Y. Al-Abed, T. L. Rothstein
Journal Articles
Immune suppression by regulatory T cells and regulatory B cells is a critical mechanism to limit excess inflammation and autoimmunity. IL-10 is considered the major mediator of B cell induced immune suppression. We report a novel mechanism for immune suppression through adenosine generation by B cells. We identified a novel population of B cells that expresses CD73 as well as CD39, two ectoenzymes that together catalyze the extracellular dephosphorylation of adenine nucleotides to adenosine. Whereas CD39 expression is common among B cells, CD73 expression is not. Approximately 30-50% of B-1 cells (B220(+)CD23(-)) and IL-10 producing B (B10) cells (B220(+)CD5(+)CD1d(hi)) are …
Perforation In A Patient With Stercoral Colitis And Diverticulosis: Who Did It?,
2014
Northwell Health
Perforation In A Patient With Stercoral Colitis And Diverticulosis: Who Did It?, V. R. Bhatt, S. Murukutla, J. Dipoce, S. Gustafson, D. Sarkany, K. Mody, W. D. Widmann, A. Gottesman
Journal Articles
Stercoral colitis with perforation of the colon is an uncommon, yet life-threatening cause of the acute abdomen. No one defining symptom exists for stercoral colitis; it may present asymptomatically or with vague symptoms. Diagnostic delay may result in perforation of the colon resulting in complications, even death. Moreover, stercoral perforation of the colon can also present with localized left lower quadrant abdominal pain masquerading as diverticulitis. Diverticular diseases and stercoral colitis share similar pathophysiology; furthermore, they may coexist, further complicating the diagnostic dilemma. The ability to decide the cause of perforation in a patient with both stercoral colitis and diverticulosis …
Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis,
2014
Northwell Health
Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors
Journal Articles
Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M ( IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early …
A Post-2011 Time Motion Study--The Authors' Reply,
2014
Zucker School of Medicine at Hofstra/Northwell
A Post-2011 Time Motion Study--The Authors' Reply, L. Block, R. Habicht, A. W. Wu, S. V. Desai, K. Wang, K. N. Silva, T. Niessen, N. Oliver, L. Feldman
Journal Articles
No abstract provided.
Rare Case Of Coronary To Pulmonary Vein Fistula With Coronary Steal Phenomenon,
2014
Northwell Health
Rare Case Of Coronary To Pulmonary Vein Fistula With Coronary Steal Phenomenon, E. A. Barsoum, F. B. Saiful, D. Asti, R. Morcus, G. Khoueiry, J. Lafferty, D. A. Mccord
Journal Articles
Coronary artery fistulas are abnormal connections between coronary artery territories and cardiac chambers or major vessels, most of them are congenital. Patients with coronary artery fistula can be asymptomatic or present with different symptoms like angina. Cardiac computed tomography (CT) is one of the best modalities for diagnosis. We present an elderly patient that presented with angina symptoms, non invasive stress test was positive for ischemic heart disease, coronary angiogram could not reveal any obstructive lesions, but an abnormal branch of the left descending coronary artery (LAD), cardiac CT showed fistula that connect left anterior descending coronary artery to left …
Recognition Of Antigen-Specific B-Cell Receptors From Chronic Lymphocytic Leukemia Patients By Synthetic Antigen Surrogates,
2014
Zucker School of Medicine at Hofstra/Northwell
Recognition Of Antigen-Specific B-Cell Receptors From Chronic Lymphocytic Leukemia Patients By Synthetic Antigen Surrogates, M. Sarkar, Y. Liu, J. Morimoto, H. Peng, C. Aquino, C. Rader, N. Chiorazzi, T. Kodadek
Journal Articles
In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with …
The Role Of Skin Trauma In The Distribution Of Morphea Lesions: A Cross-Sectional Survey Of The Morphea In Adults And Children Cohort Iv,
2014
Northwell Health
The Role Of Skin Trauma In The Distribution Of Morphea Lesions: A Cross-Sectional Survey Of The Morphea In Adults And Children Cohort Iv, D. Grabell, C. Hsieh, R. Andrew, K. Martires, A. Kim, R. Vasquez, H. Jacobe
Journal Articles
Background: Skin trauma may play a role in the development of morphea lesions. The association between trauma and the distribution of cutaneous lesions has never been examined to our knowledge. Objective: We sought to determine whether patients enrolled in the Morphea in Adults and Children (MAC) cohort exhibit skin lesions distributed in areas of prior (isotopic) or ongoing (isomorphic) trauma. Methods: This was a cross-sectional analysis of the MAC cohort. Results: Of 329 patients in the MAC cohort, 52 (16%) had trauma-associated lesions at the onset of disease. Patients with lesions in an isotopic distribution had greater clinical severity as …
Splenic B-1a Cells Expressing Cd138 Spontaneously Secrete Large Amounts Of Immunoglobulin In Naive Mice,
2014
Northwell Health
Splenic B-1a Cells Expressing Cd138 Spontaneously Secrete Large Amounts Of Immunoglobulin In Naive Mice, N. E. Holodick, T. Vizconde, T. L. Rothstein
Journal Articles
B-1a cells constitutively secrete natural antibody that provides immediate protection against microbial pathogens and functions homeostatically to speed removal of apoptotic cell debris. Although B-1a cells are especially prominent in the peritoneal and pleural cavities, some B-1a cells reside in the spleen. A small subset of splenic B-1a cells in naive, unimmunized mice express CD138, a recognized plasma cell antigen, whereas the bulk of splenic B-1a cells are CD138 negative. Splenic B-1a cells in toto have been shown to generate much more antibody per cell than peritoneal B-1a cells; however, specific functional information regarding CD138(+) splenic B-1a cells has been …
Structure And Function Of Renal Macrophages And Dendritic Cells From Lupus-Prone Mice,
2014
Northwell Health
Structure And Function Of Renal Macrophages And Dendritic Cells From Lupus-Prone Mice, R. Sahu, R. Bethunaickan, S. Singh, A. Davidson
Journal Articles
Objective. To characterize renal macrophages and dendritic cells (DCs) in 2 murine models of lupus nephritis. Methods. We used a bead-based enrichment step followed by cell sorting to isolate populations of interest from young mice and nephritic mice. Cell morphology was examined by microscopy. Arginase and nitrite production was examined using biochemical assays. The antigen-presenting functions of the cells were determined using mixed lymphocyte reactions. Selected cytokine, chemokine, and Toll-like receptor (TLR) profiles were examined using real-time quantitative polymerase chain reaction. Results. We identified 2 populations of macrophages and 3 populations of DCs in both of our murine models of …
User Centered Clinical Decision Support Tools: Adoption Across Clinician Training Level,
2014
Northwell Health
User Centered Clinical Decision Support Tools: Adoption Across Clinician Training Level, L. J. Mccullagh, A. Sofianou, J. Kannry, D. M. Mann, T. G. Mcginn
Journal Articles
BACKGROUND: Dissemination and adoption of clinical decision support (CDS) tools is a major initiative of the Affordable Care Act's Meaningful Use program. Adoption of CDS tools is multipronged with personal, organizational, and clinical settings factoring into the successful utilization rates. Specifically, the diffusion of innovation theory implies that 'early adopters' are more inclined to use CDS tools and younger physicians tend to be ranked in this category. OBJECTIVE: This study examined the differences in adoption of CDS tools across providers' training level. PARTICIPANTS: From November 2010 to 2011, 168 residents and attendings from an academic medical institution were enrolled into …
A 129-Kb Deletion On Chromosome 12 Confers Substantial Protection Against Rheumatoid Arthritis, Implicating The Gene Slc2a3,
2014
Zucker School of Medicine at Hofstra/Northwell
A 129-Kb Deletion On Chromosome 12 Confers Substantial Protection Against Rheumatoid Arthritis, Implicating The Gene Slc2a3, C. D. Veal, K. E. Reekie, J. C. Lorentzen, P. K. Gregersen, L. Padyukov, A. J. Brookes
Journal Articles
We describe a copy-number variant (CNV) for which deletion alleles confer a protective affect against rheumatoid arthritis (RA). This CNV reflects net unit deletions and expansions to a normal two-unit tandem duplication located on human chr12p13.31, a region with conserved synteny to the rat RA susceptibility quantitative trait loci Oia2. Genotyping, using the paralogue ratio test and SNP intensity data, in Swedish samples (2,403 cases, 1,269 controls) showed that the frequency of deletion variants is significantly lower in cases (P=0.0012, OR=0.442 [95%CI 0.258-0.755]). Reduced frequencies of deletion variants were also seen in replication materials comprising 9,201 UK samples (1,846 cases, …
Drivers Of Hospitalization For Patients With Atrial Fibrillation: Results From The Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation (Orbit-Af),
2014
Zucker School of Medicine at Hofstra/Northwell
Drivers Of Hospitalization For Patients With Atrial Fibrillation: Results From The Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation (Orbit-Af), B. A. Steinberg, S. Kim, G. C. Fonarow, L. Thomas, J. Ansell, P. R. Kowey, K. W. Mahaffey, B. J. Gersh, E. Hylek, Informed Outcomes Registry Better, +6 Additional Authors
Journal Articles
Background Atrial fibrillation (AF) is the most common cardiac dysrhythmia and contributes significantly to health care expenditures. We sought to assess the frequency and predictors of hospitalization in patients with AF. Methods The ORBIT-AF registry is a prospective, observational study of outpatients with AF enrolled from June 29, 2010, to August 9, 2011. The current analysis included 9,484 participants with 1-year follow-up. Multivariable, logistic regression was used to identify baseline characteristics that were associated with first cause-specific hospitalization. Results Overall, 31% of patients with AF studied (n = 2,963) had 1 or more hospitalizations per year and 10% (n = …
D-Dimer As A Predictor Of Venous Thromboembolism In Acutely Ill, Hospitalized Patients: A Subanalysis Of The Randomized Controlled Magellan Trial,
2014
Zucker School of Medicine at Hofstra/Northwell
D-Dimer As A Predictor Of Venous Thromboembolism In Acutely Ill, Hospitalized Patients: A Subanalysis Of The Randomized Controlled Magellan Trial, A. T. Cohen, T. E. Spiro, A. C. Spyropoulos, Y. H. Desanctis, M. Homering, H. R. Buller, L. Haskell, D. Hu, R. Hull, P. Burton, +4 Additional Authors
Journal Articles
Background D-dimer concentrations have not been evaluated extensively as a predictor of increased venous thromboembolism (VTE) risk in acutely ill, hospitalized medical patients. Objectives To analyze the relationships between D-dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649). Patients/methods This was a multicenter, randomized, controlled trial. Patients aged >= 40years, hospitalized for acute medical illnesses with risk factors for VTE received subcutaneous enoxaparin 40mg once daily for 10 +/- 4days then placebo up to day 35, or oral rivaroxaban 10mg once daily for 35 +/- 4days. Patients (n=7581) were grouped by baseline D-dimer2xthe upper limit of normal. VTE and …
Factors Associated With Damage Accrual In Patients With Systemic Lupus Erythematosus: Results From The Systemic Lupus International Collaborating Clinics (Slicc) Inception Cohort,
2014
Zucker School of Medicine at Hofstra/Northwell
Factors Associated With Damage Accrual In Patients With Systemic Lupus Erythematosus: Results From The Systemic Lupus International Collaborating Clinics (Slicc) Inception Cohort, I. N. Bruce, A. G. O'Keeffe, V. Farewell, J. G. Hanly, S. Manzi, L. Su, D. D. Gladman, S. C. Bae, C. Aranow, M. B. Urowitz, +30 Additional Authors
Journal Articles
BACKGROUND AND AIMS: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. RESULTS: …
Immunochip Analysis Identifies Multiple Susceptibility Loci For Systemic Sclerosis,
2014
Zucker School of Medicine at Hofstra/Northwell
Immunochip Analysis Identifies Multiple Susceptibility Loci For Systemic Sclerosis, M. D. Mayes, L. Bossini-Castillo, O. Gorlova, J. E. Martin, X. D. Zhou, W. V. Chen, S. Assassi, P. K. Gregersen, A. T. Lee, J. Martin, +66 Additional Authors
Journal Articles
In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three …
Immunochip Identifies Novel, And Replicates Known, Genetic Risk Loci For Rheumatoid Arthritis In Black South Africans,
2014
Zucker School of Medicine at Hofstra/Northwell
Immunochip Identifies Novel, And Replicates Known, Genetic Risk Loci For Rheumatoid Arthritis In Black South Africans, N. Govind, A. Choudhury, B. Hodkinson, C. Ickinger, J. Frost, A. Lee, P. K. Gregersen, R. J. Reynolds, S. L. Bridges, M. Tikly, +2 Additional Authors
Journal Articles
The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single …
Lack Of Concordance Between Empirical Scores And Physician Assessments Of Stroke And Bleeding Risk In Atrial Fibrillation Results From The Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation (Orbit-Af) Registry,
2014
Zucker School of Medicine at Hofstra/Northwell
Lack Of Concordance Between Empirical Scores And Physician Assessments Of Stroke And Bleeding Risk In Atrial Fibrillation Results From The Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation (Orbit-Af) Registry, B. A. Steinberg, S. Kim, L. Thomas, G. C. Fonarow, E. Hylek, J. Ansell, A. S. Go, P. Chang, P. Kowey, E. D. Peterson, +4 Additional Authors
Journal Articles
Background-Physicians treating patients with atrial fibrillation (AF) must weigh the benefits of anticoagulation in preventing stroke versus the risk of bleeding. Although empirical models have been developed to predict such risks, the degree to which these coincide with clinicians' estimates is unclear. Methods and Results-We examined 10 094 AF patients enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) registry between June 2010 and August 2011. Empirical stroke and bleeding risks were assessed by using the congestive heart failure, hypertension, age >= 75 years, diabetes mellitus, and previous stroke or transient ischemic attack (CHADS(2)) and Anticoagulation and …
A Role For Noncoding Variation In Schizophrenia,
2014
Zucker School of Medicine at Hofstra/Northwell
A Role For Noncoding Variation In Schizophrenia, P. Roussos, A. C. Mitchell, G. Voloudakis, J. F. Fullard, V. M. Pothula, J. Tsang, E. A. Stahl, A. Georgakopoulos, P. K. Gregersen, P. Sklar, +15 Additional Authors
Journal Articles
A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal …
Fine Mapping Major Histocompatibility Complex Associations In Psoriasis And Its Clinical Subtypes,
2014
Zucker School of Medicine at Hofstra/Northwell
Fine Mapping Major Histocompatibility Complex Associations In Psoriasis And Its Clinical Subtypes, Y. Okada, B. Han, L. C. Tsoi, P. E. Stuart, E. Ellinghaus, T. Tejasvi, V. Chandran, F. Pellett, P. K. Gregersen, S. Raychaudhuri, +12 Additional Authors
Journal Articles
Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C*06:02 demonstrated the lowest p value …
