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2015

Medical Sciences

Journal Articles

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Articles 1 - 30 of 67

Full-Text Articles in Medicine and Health Sciences

A Critical Role For The Host Mediator Macrophage Migration Inhibitory Factor In The Pathogenesis Of Malarial Anemia, M. A. Mcdevitt, J. Xie, S. Ganapathy-Kanniappan, J. Griffith, A. Liu, C. Mcdonald, P. Thuma, V. R. Gordeuk, C. N. Metz, R. Mitchell, J. Keefer, J. David, L. Leng, R. Bucala Jan 2015

A Critical Role For The Host Mediator Macrophage Migration Inhibitory Factor In The Pathogenesis Of Malarial Anemia, M. A. Mcdevitt, J. Xie, S. Ganapathy-Kanniappan, J. Griffith, A. Liu, C. Mcdonald, P. Thuma, V. R. Gordeuk, C. N. Metz, R. Mitchell, J. Keefer, J. David, L. Leng, R. Bucala

Journal Articles

No abstract provided.


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 …


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 …


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 …


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 Jan 2015

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 …


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 …


Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg Jan 2015

Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg

Journal Articles

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …


Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan Jan 2015

Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan

Journal Articles

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …


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 Jan 2015

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, S. Pathak, C. Stern, A. Vambutas Jan 2015

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, 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 Jan 2015

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, A. E. Yancoskie, D. K. Frank, J. E. Fantasia, S. Savona, N. Eiseler, I. Reder, L. B. Kahn Jan 2015

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.


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 Jan 2015

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: …


Association Of A Schizophrenia Risk Variant At The Drd2 Locus With Antipsychotic Treatment Response In First-Episode Psychosis, J. P. Zhang, D. G. Robinson, Juan Gallego, M. John, J. Yu, J. Addington, M. Tohen, John Kane, Anil Malhotra, T. Lencz Jan 2015

Association Of A Schizophrenia Risk Variant At The Drd2 Locus With Antipsychotic Treatment Response In First-Episode Psychosis, J. P. Zhang, D. G. Robinson, Juan Gallego, M. John, J. Yu, J. Addington, M. Tohen, John Kane, Anil Malhotra, T. Lencz

Journal Articles

Findings from the Psychiatric Genomics Consortium genome-wide association study (GWAS) showed that variation at the DRD2 locus is associated with schizophrenia risk. However, the functional significance of rs2514218, the top DRD2 single nucleotide polymorphism in the GWAS, is unknown. Dopamine D2 receptor binding is a common mechanism of action for all antipsychotic drugs, and DRD2 variants were related to antipsychotic response in previous studies. The present study examined whether rs2514218 genotype could predict antipsychotic response, including efficacy and adverse events, in a cohort of patients with first episode of psychosis treated with either risperidone or aripiprazole for 12 weeks. Subjects …


Clinical And Functional Outcomes After 2 Years In The Early Detection And Intervention For The Prevention Of Psychosis Multisite Effectiveness Trial, W. R. Mcfarlane, B. Levin, L. Travis, F. L. Lucas, S. Lynch, M. Verdi, Barbara Cornblatt, S. F. Taylor, A. M. Auther, E. Spring, +11 Additional Authors Jan 2015

Clinical And Functional Outcomes After 2 Years In The Early Detection And Intervention For The Prevention Of Psychosis Multisite Effectiveness Trial, W. R. Mcfarlane, B. Levin, L. Travis, F. L. Lucas, S. Lynch, M. Verdi, Barbara Cornblatt, S. F. Taylor, A. M. Auther, E. Spring, +11 Additional Authors

Journal Articles

OBJECTIVE: To test effectiveness of the Early Detection, Intervention, and Prevention of Psychosis Program in preventing the onset of severe psychosis and improving functioning in a national sample of at-risk youth. METHODS: In a risk-based allocation study design, 337 youth (age 12-25) at risk of psychosis were assigned to treatment groups based on severity of positive symptoms. Those at clinically higher risk (CHR) or having an early first episode of psychosis (EFEP) were assigned to receive Family-aided Assertive Community Treatment (FACT); those at clinically lower risk (CLR) were assigned to receive community care. Between-groups differences on outcome variables were adjusted …


Missing-In-Metastasis Regulates Cell Motility And Invasion Via Ptpdelta-Mediated Changes In Src Activity, F. Chaudhary, R. Lucito, N. K. Tonks Jan 2015

Missing-In-Metastasis Regulates Cell Motility And Invasion Via Ptpdelta-Mediated Changes In Src Activity, F. Chaudhary, R. Lucito, N. K. Tonks

Journal Articles

MIM (Missing-in-Metastasis), also known as MTSS1 (metastasis suppressor 1), is a scaffold protein that is down-regulated in multiple metastatic cancer cell lines compared with non-metastatic counterparts. MIM regulates cytoskeletal dynamics and actin polymerization, and has been implicated in the control of cell motility and invasion. MIM has also been shown to bind to a receptor PTP (protein tyrosine phosphatase), PTPdelta, an interaction that may provide a link between tyrosine-phosphorylation-dependent signalling and metastasis. We used shRNA-mediated gene silencing to investigate the consequences of loss of MIM on the migration and invasion of the MCF10A mammary epithelial cell model of breast cancer. …


High-Density Genotyping Of Immune Loci In Koreans And Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci, K. Kim, S. Y. Bang, H. S. Lee, S. K. Cho, C. B. Choi, Y. K. Sung, T. H. Kim, P. K. Gregersen, S. C. Bae, +32 Additional Authors Jan 2015

High-Density Genotyping Of Immune Loci In Koreans And Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci, K. Kim, S. Y. Bang, H. S. Lee, S. K. Cho, C. B. Choi, Y. K. Sung, T. H. Kim, P. K. Gregersen, S. C. Bae, +32 Additional Authors

Journal Articles

OBJECTIVE: A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. METHODS: We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously …


Impact Of Early Disease Factors On Metabolic Syndrome In Systemic Lupus Erythematosus: Data From An International Inception Cohort, B. Parker, M. B. Urowitz, D. D. Gladman, M. Lunt, R. Donn, S. C. Bae, J. Sanchez-Guerrero, C. Aranow, M. Mackay, I. N. Bruce, +30 Additional Authors Jan 2015

Impact Of Early Disease Factors On Metabolic Syndrome In Systemic Lupus Erythematosus: Data From An International Inception Cohort, B. Parker, M. B. Urowitz, D. D. Gladman, M. Lunt, R. Donn, S. C. Bae, J. Sanchez-Guerrero, C. Aranow, M. Mackay, I. N. Bruce, +30 Additional Authors

Journal Articles

BACKGROUND: The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE. METHODS: Recently diagnosed (<15 >months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression. RESULTS: We …


Deletion Of Stat5a/B In Vascular Smooth Muscle Abrogates The Male Bias In Hypoxic Pulmonary Hypertension In Mice: Implications In The Human Disease, Y. M. Yang, H. Yuan, J. G. Edwards, Y. Skayian, K. Ochani, E. J. Miller, P. B. Sehgal Jan 2015

Deletion Of Stat5a/B In Vascular Smooth Muscle Abrogates The Male Bias In Hypoxic Pulmonary Hypertension In Mice: Implications In The Human Disease, Y. M. Yang, H. Yuan, J. G. Edwards, Y. Skayian, K. Ochani, E. J. Miller, P. B. Sehgal

Journal Articles

Chronic hypoxia typically elicits pulmonary hypertension (PH) in mice with a male-dominant phenotype. There is an opposite sex-bias in human PH with higher prevalence in women, but greater survival (the "estrogen paradox"). We investigated the involvement of STAT5a/b species, previously established to mediate sexual dimorphism in other contexts, in the sex-bias in PH. Mice with heterozygous or homozygous deletions of the STAT5a/b locus in vascular smooth muscle cells (SMC) were generated in crosses between STAT5a/bfl/fl and transgelin (SM22alpha)-Cre+/+ parents. Wild-type (wt) males subjected to chronic hypoxia showed significant PH and pulmonary arterial remodeling, with wt females showing minimal changes (a …


Age-Dependent Alterations In The Inflammatory Response To Pulmonary Challenge, H. M. Linge, K. Ochani, K. Lin, J. Y. Lee, E. J. Miller Jan 2015

Age-Dependent Alterations In The Inflammatory Response To Pulmonary Challenge, H. M. Linge, K. Ochani, K. Lin, J. Y. Lee, E. J. Miller

Journal Articles

The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 …


Autoantibodies In Systemic Autoimmune Diseases: Specificity And Pathogenicity, J. Suurmond, B. Diamond Jan 2015

Autoantibodies In Systemic Autoimmune Diseases: Specificity And Pathogenicity, J. Suurmond, B. Diamond

Journal Articles

In this Review we focus on the initiation of autoantibody production and autoantibody pathogenicity, with a special emphasis on the targeted antigens. Release of intracellular antigens due to excessive cell death or to ineffective clearance of apoptotic debris, modification of self-antigens during inflammatory responses, and molecular mimicry contribute to the initiation of autoantibody production. We hypothesize that those autoreactive B cells that survive and produce pathogenic autoantibodies have specificity for self-antigens that are TLR ligands. Such B cells experience both B cell receptor (BCR) activation and TLR engagement, leading to an escape from tolerance. Moreover, the autoantibodies they produce form …


Antibodies As Mediators Of Brain Pathology, L. Brimberg, S. Mader, Y. Fujieda, Y. Arinuma, C. Kowal, B. T. Volpe, B. Diamond Jan 2015

Antibodies As Mediators Of Brain Pathology, L. Brimberg, S. Mader, Y. Fujieda, Y. Arinuma, C. Kowal, B. T. Volpe, B. Diamond

Journal Articles

No abstract provided.


Association Of Valine And Leucine At Hla-Drb1 Position 11 With Radiographic Progression In Rheumatoid Arthritis, Independent Of The Shared Epitope Alleles But Not Independent Of Anti-Citrullinated Protein Antibodies, H. W. Van Steenbergen, S. Raychaudhuri, L. Rodriguez-Rodriguez, S. Rantapaa-Dahlqvist, E. Berglin, R. E. M. Toes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil Jan 2015

Association Of Valine And Leucine At Hla-Drb1 Position 11 With Radiographic Progression In Rheumatoid Arthritis, Independent Of The Shared Epitope Alleles But Not Independent Of Anti-Citrullinated Protein Antibodies, H. W. Van Steenbergen, S. Raychaudhuri, L. Rodriguez-Rodriguez, S. Rantapaa-Dahlqvist, E. Berglin, R. E. M. Toes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil

Journal Articles

Objective. For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. Methods. A total of 4,911 radiograph sets from 1,878 …


B Cells In The Aging Immune System: Time To Consider B-1 Cells, N. E. Holodick, T. L. Rothstein Jan 2015

B Cells In The Aging Immune System: Time To Consider B-1 Cells, N. E. Holodick, T. L. Rothstein

Journal Articles

The investigation of immune senescence has uncovered many changes in B cell development, maintenance, and function with increasing age. However, most of these studies have focused on conventional B cell subsets in the spleen. The B-1 cell subset is an essential arm of the innate immune system, which in general has been understudied in terms of immune senescence. Here, we review what is currently known about B cells during aging and go on to describe why B-1 cell biology is an important component of the aging immune system in the context of diseases that most affect the aged population.


Brain Metabolism And Autoantibody Titres Predict Functional Impairment In Systemic Lupus Erythematosus, M. Mackay, C. C. Tang, B. T. Volpe, C. Aranow, P. J. Mattis, R. A. Korff, B. Diamond, D. Eidelberg Jan 2015

Brain Metabolism And Autoantibody Titres Predict Functional Impairment In Systemic Lupus Erythematosus, M. Mackay, C. C. Tang, B. T. Volpe, C. Aranow, P. J. Mattis, R. A. Korff, B. Diamond, D. Eidelberg

Journal Articles

OBJECTIVE: We investigated whether systemic lupus erythematosus (SLE) disease duration or serology associate with abnormal regional glucose metabolism as measured with [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and deficits on neuropsychological testing. METHODS: Subjects with SLE with stable disease activity, without brain damage or clinical symptoms of neuropsychiatric (NP) SLE, stratified by disease duration (short-term (ST)-SLE=disease/=10 years), underwent clinical assessments, neuropsychological testing, resting FDG-PET scan imaging and measurement of serum titres of antibody to N-methyl-d-aspartate receptor (DNRAb). FDG-PET scans were compared with age-matched and gender-matched healthy controls. RESULTS: Subjects with LT-SLE demonstrated hypometabolism in the prefrontal and premotor cortices that correlated …


The Brighter (And Evolutionarily Older) Face Of The Metabolic Syndrome: Evidence From Trypanosoma Cruzi Infection In Cd-1 Mice, W. Brima, D. J. Eden, S. F. Mehdi, M. Bravo, M. M. Wiese, J. Stein, V. Almonte, D. Zhao, J. Roth, F. Nagajyothi, +5 Additional Authors Jan 2015

The Brighter (And Evolutionarily Older) Face Of The Metabolic Syndrome: Evidence From Trypanosoma Cruzi Infection In Cd-1 Mice, W. Brima, D. J. Eden, S. F. Mehdi, M. Bravo, M. M. Wiese, J. Stein, V. Almonte, D. Zhao, J. Roth, F. Nagajyothi, +5 Additional Authors

Journal Articles

BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 …


The Cation Channel Trpv2 Is A New Suppressor Of Arthritis Severity, Joint Damage, And Synovial Fibroblast Invasion, T. Laragione, K. F. Cheng, M. R. Tanner, M. He, C. Beeton, Y. Al-Abed, P. S. Gulko Jan 2015

The Cation Channel Trpv2 Is A New Suppressor Of Arthritis Severity, Joint Damage, And Synovial Fibroblast Invasion, T. Laragione, K. F. Cheng, M. R. Tanner, M. He, C. Beeton, Y. Al-Abed, P. S. Gulko

Journal Articles

Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1beta-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and …


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 Jan 2015

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. …


Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America, D. Wofsy, B. Diamond, F. A. Houssiau Jan 2015

Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America, D. Wofsy, B. Diamond, F. A. Houssiau

Journal Articles

No abstract provided.


Functional Loss Of I Kappa B Epsilon Leads To Nf-Kappa B Deregulation In Aggressive Chronic Lymphocytic Leukemia, L. Mansouri, L. A. Sutton, V. Ljungstrom, S. Bondza, L. Arngarden, S. Bhoi, X. J. Yan, N. Chiorazzi, R. Rosenquist, +25 Additional Authors Jan 2015

Functional Loss Of I Kappa B Epsilon Leads To Nf-Kappa B Deregulation In Aggressive Chronic Lymphocytic Leukemia, L. Mansouri, L. A. Sutton, V. Ljungstrom, S. Bondza, L. Arngarden, S. Bhoi, X. J. Yan, N. Chiorazzi, R. Rosenquist, +25 Additional Authors

Journal Articles

NF-kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-kappa B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I kappa B epsilon, a negative regulator of NF-kappa B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic …