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Articles 151 - 180 of 290
Full-Text Articles in Medical 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
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.
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
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
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 …
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
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
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
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
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
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 …
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
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 …
Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America, D. Wofsy, B. Diamond, F. A. Houssiau
Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America, D. Wofsy, B. Diamond, F. A. Houssiau
Journal Articles
No abstract provided.
Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients, I. C. Hirako, C. Gallego-Marin, M. A. Ataide, W. A. Andrade, H. Gravina, B. C. Rocha, R. B. De Oliveira, D. B. Pereira, B. Diamond, R. T. Gazzinelli, +3 Additional Authors
Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients, I. C. Hirako, C. Gallego-Marin, M. A. Ataide, W. A. Andrade, H. Gravina, B. C. Rocha, R. B. De Oliveira, D. B. Pereira, B. Diamond, R. T. Gazzinelli, +3 Additional Authors
Journal Articles
High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-kappaB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-alpha] and interleukin-1beta [IL-1beta])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14(+) CD16 (FcgammaRIIIA)(+) CD64 (FcgammaRI)(high) CD32 (FcgammaRIIB)(low) monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14(+) …
Genome-Wide Association Study Identifies Hla 8.1 Ancestral Haplotype Alleles As Major Genetic Risk Factors For Myositis Phenotypes, F. W. Miller, W. Chen, T. P. O'Hanlon, R. G. Cooper, J. Vencovsky, L. G. Rider, K. Danko, A. Lee, P. K. Gregersen, C. I. Amos, +17 Additional Authors
Genome-Wide Association Study Identifies Hla 8.1 Ancestral Haplotype Alleles As Major Genetic Risk Factors For Myositis Phenotypes, F. W. Miller, W. Chen, T. P. O'Hanlon, R. G. Cooper, J. Vencovsky, L. G. Rider, K. Danko, A. Lee, P. K. Gregersen, C. I. Amos, +17 Additional Authors
Journal Articles
Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P10-8) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for …
A Genetic Study On C5-Traf1 And Progression Of Joint Damage In Rheumatoid Arthritis, H. W. Van Steenbergen, L. Rodriguez-Rodriguez, E. Berglin, A. Zhernakova, R. Knevel, J. Ivorra-Cortes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil, +1 Additional Author
A Genetic Study On C5-Traf1 And Progression Of Joint Damage In Rheumatoid Arthritis, H. W. Van Steenbergen, L. Rodriguez-Rodriguez, E. Berglin, A. Zhernakova, R. Knevel, J. Ivorra-Cortes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil, +1 Additional Author
Journal Articles
Introduction: The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts. Methods: In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), …
Genome-Wide Association Analysis Of Psoriatic Arthritis And Cutaneous Psoriasis Reveals Differences In Their Genetic Architecture, P. E. Stuart, R. P. Nair, L. C. Tsoi, T. Tejasvi, S. Das, H. M. Kang, E. Ellinghaus, V. Chandran, K. Callis-Duffin, R. Ike, Y. Li, X. Wen, C. Enerback, J. E. Gudjonsson, S. Koks, K. Kingo, J. Winkelmann, P. K. Gregersen, J. T. Elder, +30 Additional Authors
Genome-Wide Association Analysis Of Psoriatic Arthritis And Cutaneous Psoriasis Reveals Differences In Their Genetic Architecture, P. E. Stuart, R. P. Nair, L. C. Tsoi, T. Tejasvi, S. Das, H. M. Kang, E. Ellinghaus, V. Chandran, K. Callis-Duffin, R. Ike, Y. Li, X. Wen, C. Enerback, J. E. Gudjonsson, S. Koks, K. Kingo, J. Winkelmann, P. K. Gregersen, J. T. Elder, +30 Additional Authors
Journal Articles
Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with …
A Large-Scale Genetic Analysis Reveals A Strong Contribution Of The Hla Class Ii Region To Giant Cell Arteritis Susceptibility, F. D. Carmona, S. L. Mackie, J. E. Martin, J. C. Taylor, A. Vaglio, S. Eyre, L. Bossini-Castillo, S. Castaneda, P. K. Gregersen, G. C. A. Grp Spanish, +64 Additional Authors
A Large-Scale Genetic Analysis Reveals A Strong Contribution Of The Hla Class Ii Region To Giant Cell Arteritis Susceptibility, F. D. Carmona, S. L. Mackie, J. E. Martin, J. C. Taylor, A. Vaglio, S. Eyre, L. Bossini-Castillo, S. Castaneda, P. K. Gregersen, G. C. A. Grp Spanish, +64 Additional Authors
Journal Articles
We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 x 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DR beta 1 and …
Robotics: A Rehabilitation Modality, H. I. Krebs, B. T. Volpe
Robotics: A Rehabilitation Modality, H. I. Krebs, B. T. Volpe
Journal Articles
No abstract provided.
Stat5a/B Contribute To Sex Bias In Vascular Disease: A Neuroendocrine Perspective, P.B. Sehgal, Y. Yang, H. Yuan, E.J. Miller
Stat5a/B Contribute To Sex Bias In Vascular Disease: A Neuroendocrine Perspective, P.B. Sehgal, Y. Yang, H. Yuan, E.J. Miller
Journal Articles
No abstract provided.
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
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
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 …
Antibodies As Mediators Of Brain Pathology, L. Brimberg, S. Mader, Y. Fujieda, Y. Arinuma, C. Kowal, B. T. Volpe, B. Diamond
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.
Autoantibodies In Systemic Autoimmune Diseases: Specificity And Pathogenicity, J. Suurmond, B. Diamond
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 …
B Cells In The Aging Immune System: Time To Consider B-1 Cells, N. E. Holodick, T. L. Rothstein
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
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
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 …
Calhm1 Deletion In Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, And Life Span, G. Hellekant, J. Schmolling, P. Marambaud, T. A. Rose-Hellekant
Calhm1 Deletion In Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, And Life Span, G. Hellekant, J. Schmolling, P. Marambaud, T. A. Rose-Hellekant
Journal Articles
Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, …
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
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 …
Defects In Germinal Center Selection In Sle, M. Woods, Y. R. Zou, A. Davidson
Defects In Germinal Center Selection In Sle, M. Woods, Y. R. Zou, A. Davidson
Journal Articles
Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the LZ for further rounds of selection. Tolerance to autoantigens is frequently lost de novo as GC B cells undergo class switching and somatic mutation. This loss of tolerance is regulated by a variety of mechanisms including cell death, failure to compete for T cell help, and failure to …
Enrichment Of Genetic Variants For Rheumatoid Arthritis Within T-Cell And Nk-Cell Enhancer Regions, J. Freudenberg, P. Gregersen, W. Li
Enrichment Of Genetic Variants For Rheumatoid Arthritis Within T-Cell And Nk-Cell Enhancer Regions, J. Freudenberg, P. Gregersen, W. Li
Journal Articles
To identify disease-causative variants, we intersected the published results of a metaanalysis of genome-wide association studies (GWAS) for rheumatoid arthritis (RA) with the set of enhancer regions for 71 primary cell types that was provided by the FANTOM consortium. We first retrieved all single nucleotide polymorphisms (SNPs) that are associated (P < 5 x 10(8)) with RA in the GWAS meta-analysis and that are located in any of these enhancer regions. After excluding the major histocompatibility complex (MHC) region, we identified 50 such RA-associated SNPs that are located in enhancer regions. Enhancer sets from different cell types were then compared with each other for their number of RA-associated SNPs by permutation analysis. This analysis showed that RA-associated SNPs are preferentially located in enhancers from several immunological cell types. In particular, we see a strong relative enrichment in enhancer regions that are active in T cells (P < 0.001) and NK cells (P < 0.001). Several loci display multiple RA-associated SNPs in tight linkage disequilibrium that are located within the same or neighboring enhancers. These haplotypes may have a greater likelihood to influence enhancer activity than any SNP on its own. Taken together, these results support the hypothesis that RA-causative variants often act through altering the activity of immune cell enhancers. The enrichment in T-cell and NK-cell enhancer regions indicates that expression changes in these cell types are particularly relevant for the pathogenesis of RA. The specific SNPs that account for this enrichment can be used as a basis for focused genotype-phenotype studies of these cell types.
Excessive Antigen Reactivity May Underlie The Clinical Aggressiveness Of Chronic Lymphocytic Leukemia Stereotyped Subset #8, M. Gounari, S. Ntoufa, B. Apollonio, N. Papakonstantinou, M. Ponzoni, C. C. Chu, D. Rossi, G. Gaidano, N. Chiorazzi, P. Ghia, +1 Additional Author
Excessive Antigen Reactivity May Underlie The Clinical Aggressiveness Of Chronic Lymphocytic Leukemia Stereotyped Subset #8, M. Gounari, S. Ntoufa, B. Apollonio, N. Papakonstantinou, M. Ponzoni, C. C. Chu, D. Rossi, G. Gaidano, N. Chiorazzi, P. Ghia, +1 Additional Author
Journal Articles
Subset #8 is a distinctive subset of patients with chronic lymphocytic leukemia (CLL) defined by the expression of stereotyped IGHV4-39/IGKV1(D)-39 B-cell receptors. Subset #8 patients experience aggressive disease and exhibit the highest risk for Richter transformation among all CLL. In order to obtain biological insight into this behavior, we profiled the antigen reactivity and signaling capacity of subset #8 vs other clinically aggressive stereotyped subsets, namely subsets #1 and #2. Twenty-seven monoclonal antibodies (mAbs) from subsets #1, #2, and #8 CLL clones were prepared as recombinant human immunoglobulin G1 and used as primary antibodies in enzyme-linked immuno-sorbent assays against representatives …
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
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 …