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2015

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Outer Retinal Tubulation In Advanced Age-Related Macular Degeneration: Optical Coherence Tomographic Findings Correspond To Histology, K. B. Schaal, K. B. Freund, K. M. Litts, Y. Zhang, J. D. Messinger, C. A. Curcio Jan 2015

Outer Retinal Tubulation In Advanced Age-Related Macular Degeneration: Optical Coherence Tomographic Findings Correspond To Histology, K. B. Schaal, K. B. Freund, K. M. Litts, Y. Zhang, J. D. Messinger, C. A. Curcio

Journal Articles

PURPOSE: To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration in patients and in postmortem specimens, with particular attention to the basis of the hyperreflective border of ORT. METHOD: A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced age-related macular degeneration were compared to high-resolution histologic sections through the fovea and superior perifovea of donor eyes (13 atrophic age-related macular degeneration and 40 neovascular age-related macular degeneration) preserved

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Image Artifacts In Optical Coherence Tomography Angiography, R. F. Spaide, J. G. Fujimoto, N. K. Waheed Jan 2015

Image Artifacts In Optical Coherence Tomography Angiography, R. F. Spaide, J. G. Fujimoto, N. K. Waheed

Journal Articles

PURPOSE: To describe image artifacts of optical coherence tomography (OCT) angiography and their underlying causative mechanisms. To establish a common vocabulary for the artifacts observed. METHODS: The methods by which OCT angiography images are acquired, generated, and displayed are reviewed as are the mechanisms by which each or all of these methods can produce extraneous image information. A common set of terminology is proposed and used. RESULTS: Optical coherence tomography angiography uses motion contrast to image blood flow and thereby images the vasculature without the need for a contrast agent. Artifacts are very common and can arise from the OCT …

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Effects Of Wharton's Jelly-Derived Mesenchymal Stem Cells On Neonatal Neutrophils, I. Khan, L. Zhang, M. Mohammed, F. E. Archer, J. Abukharmah, Z. Yuan, S. S. Rizvi, M. G. Melek, B. Weinberger, A. M. Vetrano, +2 Additional Authors Jan 2015

Effects Of Wharton's Jelly-Derived Mesenchymal Stem Cells On Neonatal Neutrophils, I. Khan, L. Zhang, M. Mohammed, F. E. Archer, J. Abukharmah, Z. Yuan, S. S. Rizvi, M. G. Melek, B. Weinberger, A. M. Vetrano, +2 Additional Authors

Journal Articles

BACKGROUND: Mesenchymal stem cells (MSCs) have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton's jelly (WJ-MSCs) are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known. We compared the effects of WJ-MSCs on apoptosis and the expression of inflammatory, oxidant, and antioxidant mediators in adult and neonatal neutrophils. METHODS: WJ-MSCs were isolated, and their purity and function were confirmed by flow cytometry. Neutrophils were isolated from cord and adult blood by density centrifugation. The effects of neutrophil/WJ-MSC co-culture on apoptosis and gene and protein expression …

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The Erythroblastic Island As An Emerging Paradigm In The Anemia Of Inflammation, J. Hom, B. M. Dulmovits, N. Mohandas, L. Blanc Jan 2015

The Erythroblastic Island As An Emerging Paradigm In The Anemia Of Inflammation, J. Hom, B. M. Dulmovits, N. Mohandas, L. Blanc

Journal Articles

Terminal erythroid differentiation occurs in the bone marrow, within specialized niches termed erythroblastic islands. These functional units consist of a macrophage surrounded by differentiating erythroblasts and have been described more than five decades ago, but their function in the pathophysiology of erythropoiesis has remained unclear until recently. Here we propose that the central macrophage in the erythroblastic island contributes to the pathophysiology of anemia of inflammation. After introducing erythropoiesis and the interactions between the erythroblasts and the central macrophage within the erythroblastic islands, we will discuss the immunophenotypic characterization of this specific subpopulation of macrophages. We will then integrate these …

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Mutations In Ddx3x Are A Common Cause Of Unexplained Intellectual Disability With Gender-Specific Effects On Wnt Signaling, L. Snijders Blok, E. Madsen, J. Juusola, C. Gilissen, D. Baralle, M. R. Reijnders, H. Venselaar, J. Fox, J. Mclaughlin, T. Kleefstra, +73 Additional Authors Jan 2015

Mutations In Ddx3x Are A Common Cause Of Unexplained Intellectual Disability With Gender-Specific Effects On Wnt Signaling, L. Snijders Blok, E. Madsen, J. Juusola, C. Gilissen, D. Baralle, M. R. Reijnders, H. Venselaar, J. Fox, J. Mclaughlin, T. Kleefstra, +73 Additional Authors

Journal Articles

Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common …

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Obtaining Research Biopsies During Pediatric Colonoscopy: Safety And Adverse Events, J. Mait-Kaufman, S. Kahn, G. Tomer Jan 2015

Obtaining Research Biopsies During Pediatric Colonoscopy: Safety And Adverse Events, J. Mait-Kaufman, S. Kahn, G. Tomer

Journal Articles

AIM: To investigate the safety profile of acquiring additional intestinal biopsies for research purposes in children undergoing a medically indicated colonoscopy. METHODS: A retrospective review of 122 pediatric patients who underwent colonoscopy over a 9 mo time period was completed. 38/122 participants consented to a research study in which 4 additional biopsies were obtained, in addition to routine biopsies. The outcomes after colonoscopy were measured in the research participants, and compared to 84 control participants who did not consent for the study. Groups were compared with regard to number of biopsies obtained, underlying diagnosis, and both serious and minor adverse …

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Effects Of Levodopa On Regional Cerebral Metabolism And Blood Flow, J. H. Ko, R. P. Lerner, D. Eidelberg Jan 2015

Effects Of Levodopa On Regional Cerebral Metabolism And Blood Flow, J. H. Ko, R. P. Lerner, D. Eidelberg

Journal Articles

Levodopa (l-dopa) has been at the forefront of antiparkinsonian therapy for a half century. Recent advances in functional brain imaging have contributed substantially to the understanding of the effects of l-dopa and other dopaminergic treatment on the activity of abnormal motor and cognitive brain circuits in Parkinson's disease patients. Progress has also been made in understanding the functional pathology of dyskinesias, a common side effect of l-dopa treatment, at both regional and network levels. Here, we review these studies, focusing mainly on the new mechanistic insights provided by metabolic brain imaging and network analysis. (c) 2014 International Parkinson and Movement …

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Reproducibility Of A Parkinsonism-Related Metabolic Brain Network In Non-Human Primates: A Descriptive Pilot Study With Fdg Pet, Y. L. Ma, T. H. Johnston, S. C. Peng, C. T. Zuo, J. B. Koprich, S. H. Fox, Y. H. Guan, D. Eidelberg, J. M. Brotchie Jan 2015

Reproducibility Of A Parkinsonism-Related Metabolic Brain Network In Non-Human Primates: A Descriptive Pilot Study With Fdg Pet, Y. L. Ma, T. H. Johnston, S. C. Peng, C. T. Zuo, J. B. Koprich, S. H. Fox, Y. H. Guan, D. Eidelberg, J. M. Brotchie

Journal Articles

Background: We have previously defined a parkinsonism-related metabolic brain network in rhesus macaques using a high-resolution research positron emission tomography camera. This brief article reports a descriptive pilot study to assess the reproducibility of network activity and regional glucose metabolism in independent parkinsonian macaques using a clinical positron emission tomography/CT camera. Methods: [F-18]fluorodeoxyglucose PET scans were acquired longitudinally over 3 months in three drug-naive parkinsonian and three healthy control cynomolgus macaques. Group difference and test-retest stability in network activity and regional glucose metabolism were evaluated graphically, using all brain images from these macaques. Results: Comparing the parkinsonian macaques with the …

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Abnormal Metabolic Pattern Associated With Cognitive Impairment In Parkinson's Disease: A Validation Study, S. K. Meles, C. C. Tang, L. K. Teune, R. A. Dierckx, V. Dhawan, P. J. Mattis, K. L. Leenders, D. Eidelberg Jan 2015

Abnormal Metabolic Pattern Associated With Cognitive Impairment In Parkinson's Disease: A Validation Study, S. K. Meles, C. C. Tang, L. K. Teune, R. A. Dierckx, V. Dhawan, P. J. Mattis, K. L. Leenders, D. Eidelberg

Journal Articles

Cognitive deficits in Parkinson's disease (PD) have been associated with a specific metabolic covariance pattern. Although the expression of this PD cognition-related pattern (PDCP) correlates with neuropsychological performance, it is not known whether the PDCP topography is reproducible across PD populations. We therefore sought to identify a PDCP topography in a new sample comprised of 19 Dutch PD subjects. Network analysis of metabolic scans from these individuals revealed a significant PDCP that resembled the original network topography. Expression values for the new PDCP correlated (P = 0.001) with executive dysfunction on the Frontal Assessment Battery (FAB). Subject scores for the …

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The Visual Perception Of Natural Motion: Abnormal Task-Related Neural Activity In Dyt1 Dystonia, W. Sako, K. Fujita, A. Vo, J. C. Rucker, J. R. Rizzo, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg Jan 2015

The Visual Perception Of Natural Motion: Abnormal Task-Related Neural Activity In Dyt1 Dystonia, W. Sako, K. Fujita, A. Vo, J. C. Rucker, J. R. Rizzo, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg

Journal Articles

Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of …

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Antigen-Based Immunotherapy For Autoimmune Disease: Current Status, D. L. Hirsch, P. Ponda Jan 2015

Antigen-Based Immunotherapy For Autoimmune Disease: Current Status, D. L. Hirsch, P. Ponda

Journal Articles

Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred signifcant clinical benefts, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifcally target disease-associated antigens and limit systemic side effects. Similar to allergen-specifc immunotherapy for allergic rhinitis, antigen-specifc immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specifc antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts …

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Assessing The Associations Of Sodium Intake With Long-Term All-Cause And Cardiovascular Mortality In A Hypertensive Cohort, P. Singer, H. Cohen, M. Alderman Jan 2015

Assessing The Associations Of Sodium Intake With Long-Term All-Cause And Cardiovascular Mortality In A Hypertensive Cohort, P. Singer, H. Cohen, M. Alderman

Journal Articles

BACKGROUND: Although higher sodium intake is known to increase blood pressure, its association with cardiovascular mortality is less established. We examined the association of baseline sodium intake in a hypertensive cohort with all-cause and cardiovascular mortality over a mean follow-up of 18.6 years. METHODS: Three thousand five hundred five subjects were participants in a worksite hypertension program. Sodium intake was estimated by 24-hour urine excretion. Mortality data were obtained from the U.S. National Death Index. Unadjusted and multivariable-adjusted associations between sodium quartiles (quartile I (QI) to quartile IV (QIV)) and mortality were assessed using Cox models. RESULTS: Estimated mean +/- …

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Calhm1 Ion Channel Elicits Amyloid-Beta Clearance By Insulin-Degrading Enzyme In Cell Lines And In Vivo In The Mouse Brain, V. Vingtdeux, P. Chandakkar, H. Zhao, L. Blanc, S. Ruiz, P. Marambaud Jan 2015

Calhm1 Ion Channel Elicits Amyloid-Beta Clearance By Insulin-Degrading Enzyme In Cell Lines And In Vivo In The Mouse Brain, V. Vingtdeux, P. Chandakkar, H. Zhao, L. Blanc, S. Ruiz, P. Marambaud

Journal Articles

Alzheimer's disease is characterized by amyloid-beta (Abeta) peptide accumulation in the brain. CALHM1, a cell-surface Ca(2+) channel expressed in brain neurons, has anti-amyloidogenic properties in cell cultures. Here, we show that CALHM1 controls Abeta levels in vivo in the mouse brain through a previously unrecognized mechanism of regulation of Abeta clearance. Using pharmacological and genetic approaches in cell lines, we found that CALHM1 ion permeability and extracellular Ca(2+) were required for the Abeta-lowering effect of CALHM1. Abeta level reduction by CALHM1 could be explained by an increase in extracellular Abeta degradation by insulin-degrading enzyme (IDE), extracellular secretion of which was …

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At(1)R Blockade In Adverse Milieus: Role Of Smrt And Corepressor Complexes, T. Singh, K. Ayasolla, P. Rai, N. Chandel, S. Haque, R. Lederman, M. Husain, V. Vethantham, A. Chawla, H. Vashistha, M. A. Saleem, G. Ding, P. N. Chander, A. Malhotra, L. G. Meggs, P. C. Singhal Jan 2015

At(1)R Blockade In Adverse Milieus: Role Of Smrt And Corepressor Complexes, T. Singh, K. Ayasolla, P. Rai, N. Chandel, S. Haque, R. Lederman, M. Husain, V. Vethantham, A. Chawla, H. Vashistha, M. A. Saleem, G. Ding, P. N. Chander, A. Malhotra, L. G. Meggs, P. C. Singhal

Journal Articles

ANG II type 1 receptor blockade (AT(1)R-BLK) is used extensively to slow down the progression of proteinuric kidney diseases. We hypothesized that AT(1)R-BLK provides podocyte protection through regulation of silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and vitamin D receptor (VDR) expression under adverse milieus such as high glucose and human immunodeficiency virus infection. Both AT(1)R-BLK and VDR agonists (VDAs) stimulated VDR complex formation that differed not only in their composition but also in their functionality. AT(1)R-BLK-induced VDR complexes contained predominantly unliganded VDR, SMRT, and phosphorylated histone deacetylase 3, whereas VDA-VDR complexes were constituted by liganded VDR …

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Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?, D. Tuveson, K. R. Rai Jan 2015

Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?, D. Tuveson, K. R. Rai

Journal Articles

No abstract provided.

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Clinical Markers Of Crohn's Disease Severity And Their Association With Opiate Use, M. Cheung, S. Khan, M. Akerman, C. K. Hung, K. Vennard, N. Hristis, K. Sultan Jan 2015

Clinical Markers Of Crohn's Disease Severity And Their Association With Opiate Use, M. Cheung, S. Khan, M. Akerman, C. K. Hung, K. Vennard, N. Hristis, K. Sultan

Journal Articles

BACKGROUND: The safety of opiate use for patients with Crohn's disease (CD) has long been a concern. The recent Crohn's therapy, resource, evaluation, and assessment tool (TREAT) registry update has added to these concerns by demonstrating an association of opiate use with an increased risk of infection and death in CD. While the association is clear, the relationship of opiates to these negative outcomes is not. It is unknown whether opiates are a contributing factor to these negative outcomes or if their use is merely a marker of more severe disease. We hypothesized that opiate use is not harmful in …

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Maternal Antibodies And Developing Blood-Brain Barrier, C. Kowal, A. Athanassiou, H. Chen, B. Diamond Jan 2015

Maternal Antibodies And Developing Blood-Brain Barrier, C. Kowal, A. Athanassiou, H. Chen, B. Diamond

Journal Articles

No abstract provided.

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Md-2 Is Required For Disulfide Hmgb1-Dependent Tlr4 Signaling, H. Yang, H. Wang, Z. Ju, A. A. Ragab, W. Long, S. I. Valdes-Ferrer, M. He, J. Li, B. Lu, J. Roth, S. S. Chavan, K. J. Tracey, Y. Al-Abed, +10 Additional Authors Jan 2015

Md-2 Is Required For Disulfide Hmgb1-Dependent Tlr4 Signaling, H. Yang, H. Wang, Z. Ju, A. A. Ragab, W. Long, S. I. Valdes-Ferrer, M. He, J. Li, B. Lu, J. Roth, S. S. Chavan, K. J. Tracey, Y. Al-Abed, +10 Additional Authors

Journal Articles

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. …

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Modular Analysis Of Peripheral Blood Gene Expression In Rheumatoid Arthritis Captures Reproducible Gene Expression Changes In Tumor Necrosis Factor Responders, M. Oswald, M. E. Curran, S. L. Lamberth, R. M. Townsend, J. D. Hamilton, D. N. Chernoff, M. Kern, C. M. Pond, A. Lee, P. K. Gregersen, +3 Additional Authors Jan 2015

Modular Analysis Of Peripheral Blood Gene Expression In Rheumatoid Arthritis Captures Reproducible Gene Expression Changes In Tumor Necrosis Factor Responders, M. Oswald, M. E. Curran, S. L. Lamberth, R. M. Townsend, J. D. Hamilton, D. N. Chernoff, M. Kern, C. M. Pond, A. Lee, P. K. Gregersen, +3 Additional Authors

Journal Articles

Objective. To establish whether the analysis of whole-blood gene expression is useful in predicting or monitoring response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). Methods. Whole-blood RNA (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti-TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules. Results. Good and moderate responders according to the European League …

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Mood Disorders In Systemic Lupus Erythematosus: Results From An International Inception Cohort Study, J. G. Hanly, L. Su, M. B. Urowitz, J. Romero-Diaz, C. Gordon, S. C. Bae, S. Bernatsky, A. E. Clarke, C. Aranow, V. Farewell, +32 Additional Authors Jan 2015

Mood Disorders In Systemic Lupus Erythematosus: Results From An International Inception Cohort Study, J. G. Hanly, L. Su, M. B. Urowitz, J. Romero-Diaz, C. Gordon, S. C. Bae, S. Bernatsky, A. E. Clarke, C. Aranow, V. Farewell, +32 Additional Authors

Journal Articles

ObjectiveTo examine the frequency, characteristics, and outcome of mood disorders, as well as clinical and autoantibody associations, in a multiethnic/racial, prospective inception cohort of patients with systemic lupus erythematosus (SLE). MethodsPatients were assessed annually for mood disorders (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 18 other neuropsychiatric events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 subscales, mental and physical component summary scores were collected. Time to event, linear and ordinal regressions, and …

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Not All Ighv3-21 Chronic Lymphocytic Leukemias Are Equal: Prognostic Considerations, P. Baliakas, A. Agathangelidis, A. Hadzidimitriou, L. A. Sutton, E. Minga, A. Tsanousa, X. J. Yan, C. C. Chu, N. Chiorazzi, K. Stamatopoulos, +38 Additional Authors Jan 2015

Not All Ighv3-21 Chronic Lymphocytic Leukemias Are Equal: Prognostic Considerations, P. Baliakas, A. Agathangelidis, A. Hadzidimitriou, L. A. Sutton, E. Minga, A. Tsanousa, X. J. Yan, C. C. Chu, N. Chiorazzi, K. Stamatopoulos, +38 Additional Authors

Journal Articles

An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No …

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The Osteopontin Transgenic Mouse Is A New Model For Sjogren's Syndrome, S. Husain-Krautter, J. M. Kramer, W. T. Li, B. C. Guo, T. L. Rothstein Jan 2015

The Osteopontin Transgenic Mouse Is A New Model For Sjogren's Syndrome, S. Husain-Krautter, J. M. Kramer, W. T. Li, B. C. Guo, T. L. Rothstein

Journal Articles

Osteopontin (Opn) is a cytokine involved in both physiological and pathological processes, and is elevated in many autoimmune diseases. Sjogren's syndrome (SS) is an autoimmune disease with a strong female predilection characterized by lymphocytic infiltration of exocrine glands. We hypothesized that Opn contributes to SS pathogenesis. We examined an established SS model and found increased Opn locally and systemically. Next, we examined Opn transgenic (Opn Tg) mice for evidence of SS. Opn Tg animals exhibited lymphocytic infiltration of salivary and lacrimal glands, and Opn co-localized with the infiltrates. Moreover, saliva production was reduced, and SS autoantibodies were observed in the …

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Partitioning Heritability By Functional Annotation Using Genome-Wide Association Summary Statistics, H. K. Finucane, B. Bulik-Sullivan, A. Gusev, G. Trynka, Y. Reshef, P. R. Loh, V. Anttila, S. Purcell, E. Stahl, A. L. Price, +12 Additional Authors Jan 2015

Partitioning Heritability By Functional Annotation Using Genome-Wide Association Summary Statistics, H. K. Finucane, B. Bulik-Sullivan, A. Gusev, G. Trynka, Y. Reshef, P. R. Loh, V. Anttila, S. Purcell, E. Stahl, A. L. Price, +12 Additional Authors

Journal Articles

Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include …

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Randomized, Double-Blind, Placebo-Controlled Trial Of The Effect Of Vitamin D3 On The Interferon Signature In Patients With Systemic Lupus Erythematosus, C. Aranow, D. L. Kamen, M. Dall'era, E. M. Massarotti, M. C. Mackay, F. Koumpouras, A. Coca, W. W. Chatham, M. E. Clowse, L. G. Criscione-Schreiber, S. Callahan, E. A. Goldmuntz, L. Keyes-Elstein, M. Oswald, P. K. Gregersen, B. Diamond Jan 2015

Randomized, Double-Blind, Placebo-Controlled Trial Of The Effect Of Vitamin D3 On The Interferon Signature In Patients With Systemic Lupus Erythematosus, C. Aranow, D. L. Kamen, M. Dall'era, E. M. Massarotti, M. C. Mackay, F. Koumpouras, A. Coca, W. W. Chatham, M. E. Clowse, L. G. Criscione-Schreiber, S. Callahan, E. A. Goldmuntz, L. Keyes-Elstein, M. Oswald, P. K. Gregersen, B. Diamond

Journal Articles

OBJECTIVE: Vitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE. METHODS: SLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level/=30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, …

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Rewiring Of Sigm-Mediated Intracellular Signaling Through The Cd180 Toll-Like Receptor, N. Porakishvili, K. Vispute, A. J. Steele, N. Rajakaruna, N. Kulikova, T. Tsertsvadze, R. N. Damle, K. R. Rai, N. Chiorazzi, P. M. Lydyard, +2 Additional Authors Jan 2015

Rewiring Of Sigm-Mediated Intracellular Signaling Through The Cd180 Toll-Like Receptor, N. Porakishvili, K. Vispute, A. J. Steele, N. Rajakaruna, N. Kulikova, T. Tsertsvadze, R. N. Damle, K. R. Rai, N. Chiorazzi, P. M. Lydyard, +2 Additional Authors

Journal Articles

Chronic lymphocytic leukemia (CLL) development and progression are thought to be driven by unknown antigens/autoantigens through the B cell receptor (BCR) and environmental signals for survival and expansion including toll-like receptor (TLR) ligands. CD180/RP105, a membrane-associated orphan receptor of the TLR family, induces normal B cell activation and proliferation and is expressed by approximately 60% of CLL samples. Half of these respond to ligation with anti-CD180 antibody by increased activation/phosphorylation of protein kinases associated with BCR signaling. Hence CLL cells expressing both CD180 and the BCR could receive signals via both receptors. Here we investigated cross-talk between BCR and CD180-mediated …

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Rodent Models Of Neuroinflammation For Alzheimer's Disease, A. Nazem, R. Sankowski, M. Bacher, Y. Al-Abed Jan 2015

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 …

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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 Jan 2015

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 …

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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 Jan 2015

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 …

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Xanomeline Suppresses Excessive Pro-Inflammatory Cytokine Responses Through Neural Signal-Mediated Pathways And Improves Survival In Lethal Inflammation, M. Rosas-Ballina, S. I. Valdes-Ferrer, M. E. Dancho, M. Ochani, D. Katz, K. F. Cheng, P. S. Olofsson, S. S. Chavan, Y. Al-Abed, K. J. Tracey, V. A. Pavlov Jan 2015

Xanomeline Suppresses Excessive Pro-Inflammatory Cytokine Responses Through Neural Signal-Mediated Pathways And Improves Survival In Lethal Inflammation, M. Rosas-Ballina, S. I. Valdes-Ferrer, M. E. Dancho, M. Ochani, D. Katz, K. F. Cheng, P. S. Olofsson, S. S. Chavan, Y. Al-Abed, K. J. Tracey, V. A. Pavlov

Journal Articles

Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer's disease …

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Influence Of A Montmorency Cherry Juice Blend On Indices Of Exercise-Induced Stress And Upper Respiratory Tract Symptoms Following Marathon Running--A Pilot Investigation, L. Dimitriou, J. A. Hill, A. Jehnali, J. Dunbar, J. Brouner, M. P. Mchugh, G. Howatson Jan 2015

Influence Of A Montmorency Cherry Juice Blend On Indices Of Exercise-Induced Stress And Upper Respiratory Tract Symptoms Following Marathon Running--A Pilot Investigation, L. Dimitriou, J. A. Hill, A. Jehnali, J. Dunbar, J. Brouner, M. P. Mchugh, G. Howatson

Journal Articles

BACKGROUND: Prolonged exercise, such as marathon running, has been associated with an increase in respiratory mucosal inflammation. The aim of this pilot study was to examine the effects of Montmorency cherry juice on markers of stress, immunity and inflammation following a Marathon. METHODS: Twenty recreational Marathon runners consumed either cherry juice (CJ) or placebo (PL) before and after a Marathon race. Markers of mucosal immunity secretory immunoglobulin A (sIgA), immunoglobulin G (IgG), salivary cortisol, inflammation (CRP) and self-reported incidence and severity of upper respiratory tract symptoms (URTS) were measured before and following the race. RESULTS: All variables except secretory IgA …

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