bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptomatology and Neuropsychological Functioning in Cannabis Using Subjects at Ultra-High Risk for Developing Psychosis and Healthy Controls
Authors: Korver Nikie , Nieman Dorien H. , Becker Hiske E. , van de Fliert J. Reinaud , Dingemans Peter H. , de Haan Lieuwe , Spiering Mark , Schmitz Nicole , Linszen Don H. 
Published: February 2010

Objective: The relationship between cannabis use and psychosis has been studied intensively. Few data, however, are available on the relationship between cannabis use, ultra-high risk for developing psychosis and neurocognition. The aim of the present cross-sectional study was therefore to investigate the relationship between cannabis use, ultra-high-risk (UHR) symptoms and cognitive functioning in UHR patients and healthy controls. Methods: A total of 63 ultra-high-risk patients (34 cannabis users) and 58 control subjects (28 cannabis users) were assessed with clinical measures and a neuropsychological test battery. Patients were eligible for the study if they were between the ages of 12 and 35 years and if they fell into one or more of the following inclusion groups: familial risk and reduced functioning, attenuated psychotic symptoms, brief limited intermittent psychotic symptoms and basic symptoms. Control subjects were eligible for the study if they were between the ages 12 and 35, had no present or past psychiatric illness, no family history of psychiatric illness, no drug use in the non-cannabis-using group, and use of at least four joints per week in the cannabis-using control group. Results: In the UHR and the control group, cannabis users experienced more basic symptoms and UHR symptoms than the non-cannabis users. Moreover, cannabis users in the control group performed at the level of the UHR subjects on a test of verbal memory and verbal fluency. Frequency of cannabis use correlated with severity of several UHR symptoms. Conclusions: Cannabis-using UHR patients have more basic symptoms than non-using patients. In addition, healthy cannabis users have more subclinical UHR and basic symptoms and more neuropsychological dysfunctions than non-cannabis users. More frequent cannabis use was related to increased severity of certain UHR symptoms.
Self-Mutilation and Suicide Attempts: Relationships to Bipolar Disorder, Borderline Personality Disorder, Temperament and Character
Authors: Joyce Peter R. , Light Katrina J. , Rowe Sarah L. , Cloninger C. Robert , Kennedy Martin A. 
Published: February 2010

Objective: Self-mutilation has traditionally been associated with borderline personality disorder, and seldom examined separately from suicide attempts. Clinical experience suggests that self-mutilation is common in bipolar disorder. Methods: A family study was conducted on the molecular genetics of depression and personality, in which the proband had been treated for depression. All probands and parents or siblings were interviewed with a structured interview and completed the Temperament and Character Inventory. Results: Fourteen per cent of subjects interviewed reported a history of self-mutilation, mostly by wrist cutting. Self-mutilation was more common in bipolar I disorder subjects then in any other diagnostic groups. In multiple logistic regression self-mutilation was predicted by mood disorder diagnosis and harm avoidance, but not by borderline personality disorder. Furthermore, the relatives of non-bipolar depressed probands with self-mutilation had higher rates of bipolar I or II disorder and higher rates of self-mutilation. Sixteen per cent of subjects reported suicide attempts and these were most common in those with bipolar I disorder and in those with borderline personality disorder. On multiple logistic regression, however, only mood disorder diagnosis and harm avoidance predicted suicide attempts. Suicide attempts, unlike self-mutilation, were not familial. Conclusions: Self-mutilation and suicide attempts are only partially overlapping behaviours, although both are predicted by mood disorder diagnosis and harm avoidance. Self-mutilation has a particularly strong association with bipolar disorder. Clinicians need to think of bipolar disorder, not borderline personality disorder, when assessing an individual who has a history of self-mutilation.
Induction of IDO-1 by Immunostimulatory DNA Limits Severity of Experimental Colitis
Authors: Ciorba Matthew A. , Bettonville Ellen E. , McDonald Keely G. , Metz Richard , Prendergast George C. , Newberry Rodney D. , Stenson William F. 
Published: February 2010

Abstract
The chronic inflammatory bowel diseases are characterized by aberrant innate and adaptive immune responses to commensal luminal bacteria. In both human inflammatory bowel disease and in experimental models of colitis, there is an increased expression of the enzyme IDO. IDO expression has the capacity to exert antimicrobial effects and dampen adaptive immune responses. In the murine trinitrobenzene sulfonic acid model of colitis, inhibition of this enzyme leads to worsened disease severity, suggesting that IDO acts as a natural break in limiting colitis. In this investigation, we show that induction of IDO-1 by a TLR-9 agonist, immunostimulatory (ISS) DNA, critically contributes to its colitis limiting capacities. ISS DNA induces intestinal expression of IDO-1 but not the recently described paralog enzyme IDO-2. This induction occurred in both epithelial cells and in subsets of CD11c+ and CD11b+ cells of the lamina propria, which also increase after ISS-oligodeoxynucleotide. Signaling required for intestinal IDO-1 induction involves IFN-dependent pathways, as IDO-1 was not induced in STAT-1 knockout mice. Using both the trinitrobenzene sulfonic acid and dextran sodium sulfate models of colitis, we show the importance of IDO-1s induction in limiting colitis severity. The clinical parameters and histological correlates of colitis in these models were improved by administration of the TLR-9 agonist; however, when the function of IDO is inhibited, the colitis limiting effects of ISS-oligodeoxynucleotide were abrogated. These findings support the possibility that targeted induction of IDO-1 is an approach deserving further investigation as a therapeutic strategy for diseases of intestinal inflammation.
TNF Activates a NF-κB–Regulated Cellular Program in Human CD45RA– Regulatory T Cells that Modulates Their Suppressive Function
Authors: Nagar Meital , Jacob-Hirsch Jasmine , Vernitsky Helly , Berkun Yackov , Ben-Horin Shomron , Amariglio Ninette , Bank Ilan , Kloog Yoel , Rechavi Gideon , Goldstein Itamar 
Published: February 2010

Abstract
Emerging data suggest that regulatory T cell (Treg) dysfunction and consequent breakdown of immunological self-tolerance in autoimmunity can be mediated by factors that are not Treg-intrinsic (e.g., cytokines). Indeed, recent studies show that in rheumatoid arthritis the proinflammatory cytokine TNF reduces the suppressive function of Tregs, whereas in vivo TNF blockade restores this function and accordingly self-tolerance. However, until now a coherent mechanism by which TNF regulates the Treg has not been described. In this paper, we show that TNF induces preferential and significant activation of the canonical NF-κB pathway in human Tregs as compared with CD25– conventional T cells. Furthermore, TNF induced primarily in CD45RA– Tregs a transcription program highly enriched for typical NF-κB target genes, such as the cytokines lymphotoxin-α and TNF, the TNFR superfamily members FAS, 4-1BB, and OX-40, various antiapoptotic genes, and other important immune-response genes. FACS analysis revealed that TNF also induced upregulation of cell surface expression of 4-1BB and OX40 specifically in CD45RA–FOXP3+ Tregs. In contrast, TNF had only a minimal effect on the Treg’s core transcriptional signature or on the intracellular levels of the FOXP3 protein in Tregs. Importantly, TNF treatment modulated the capacity of Tregs to suppress the proliferation and IFN-γ secretion by conventional T cells, an effect that was fully reversed by cotreatment with anti-TNFR2 mAbs. Our findings thus provide new mechanistic insight into the role of TNF and TNFR2 in the pathogenesis of autoimmunity.
Markers of Monocyte Activation Revealed by Lipidomic Profiling of Arachidonic Acid-Containing Phospholipids
Authors: Balgoma David , Astudillo Alma M. , Pérez-Chacón Gema , Montero Olimpio , Balboa María A. , Balsinde Jesús 
Published: February 2010

Abstract
Stimulated human monocytes undergo an intense trafficking of arachidonic acid (AA) among glycerophospholipidclasses. Using HPLC coupled to electrospray ionization mass spectrometry, we have characterized changes in the levels of AA-containing phospholipid species in human monocytes. In resting cells, AA was found esterified into various molecular species of phosphatidylinositol (PI), choline glycerophospholipids (PCs), and ethanolamine glycerophospholipids (PEs). All major AA-containing PC and PI molecular species decreased in zymosan-stimulated cells; however, no PE molecular species was found to decrease. In contrast, the levels of three AA-containing species increased in zymosan-activated cells compared with resting cells: 1,2-diarachidonyl-glycero-3-phosphoinositol [PI(20:4/20:4)]; 1,2-diarachidonyl-glycero-3-phosphocholine [PC(20:4/20:4)]; and 1-palmitoleoyl-2-arachidonyl-glycero-3-phosphoethanolamine [PE(16:1/20:4)]. PI(20:4/20:4) and PC(20:4/20:4), but not PE(16:1/20:4), also significantly increased when platelet-activating factor or PMA were used instead of zymosan to stimulate the monocytes. Analysis of the pathways involved in the synthesis of these three lipids suggest that PI(20:4/20:4) and PC(20:4/20:4) were produced in a deacylation/reacylation pathway via acyl-CoA synthetase–dependent reactions, whereas PE(16:1/20:4) was generated via a CoA-independent transacylation reaction. Collectively, our results define the increases in PI(20:4/20:4) and PC(20:4/20:4) as lipid metabolic markers of human monocyte activation and establish lipidomics as a powerful tool for cell typing under various experimental conditions.
Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation
Authors: Pedrosa Alziana Moreno da Cunha , Weinlich Ricardo , Mognol Giuliana Patricia , Robbs Bruno Kaufmann , Viola João Paulo de Biaso , Campa Ana , Amarante-Mendes Gustavo Pessini 
Published: February 2010

AbstractOver the past 20 y, the hormone melatonin was found to be produced in extrapineal sites, including cells of the immune system. Despite the increasing data regarding the biological effects of melatonin on the regulation of the immune system, the effect of this molecule on T cell survival remains largely unknown. Activation-induced cell death plays a critical role in the maintenance of the homeostasis of the immune system by eliminating self-reactive or chronically stimulated T cells. Because activated T cells not only synthesize melatonin but also respond to it, we investigated whether melatonin could modulate activation-induced cell death. We found that melatonin protects human and murine CD4+ T cells from apoptosis by inhibiting CD95 ligand mRNA and protein upregulation in response to TCR/CD3 stimulation. This inhibition is a result of the interference with calmodulin/calcineurin activation of NFAT that prevents the translocation of NFAT to the nucleus. Accordingly, melatonin has no effect on T cells transfected with a constitutively active form of NFAT capable of migrating to the nucleus and transactivating target genes in the absence of calcineurin activity. Our results revealed a novel biochemical pathway that regulates the expression of CD95 ligand and potentially other downstream targets of NFAT activation.
Matrix Metalloproteinase 12-Deficiency Augments Extracellular Matrix Degrading Metalloproteinases and Attenuates IL-13–Dependent Fibrosis
Authors: Madala Satish K. , Pesce John T. , Ramalingam Thirumalai R. , Wilson Mark S. , Minnicozzi Samantha , Cheever Allen W. , Thompson Robert W. , Mentink-Kane Margaret M. , Wynn Thomas A. 
Published: February 2010

Abstract
Infection with the parasitic helminth Schistosoma mansoni causes significant liver fibrosis and extracellular matrix (ECM) remodeling. Matrix metalloproteinases (MMP) are important regulators of the ECM by regulating cellular inflammation, extracellular matrix deposition, and tissue reorganization. MMP12 is a macrophage-secreted elastase that is highly induced in the liver and lung in response to S. mansoni eggs, confirmed by both DNA microarray and real-time PCR analysis. However, the function of MMP12 in chronic helminth-induced inflammation and fibrosis is unclear. In this study, we reveal that MMP12 acts as a potent inducer of inflammation and fibrosis after infection with the helminth parasite S. mansoni. Surprisingly, the reduction in liver and lung fibrosis in MMP12-deficient mice was not associated with significant changes in cytokine, chemokine, TGF-β1, or tissue inhibitors of matrix metalloproteinase expression. Instead, we observed marked increases in MMP2 and MMP13 expression, suggesting that Mmp12 was promoting fibrosis by limiting the expression of specific ECM-degrading MMPs. Interestingly, like MMP12, MMP13 expression was highly dependent on IL-13 and type II–IL-4 receptor signaling. However, in contrast to MMP12, expression of MMP13 was significantly suppressed by the endogenous IL-13 decoy receptor, IL-13Rα2. In the absence of MMP12, expression of IL-13Rα2 was significantly reduced, providing a possible explanation for the increased IL-13-driven MMP13 activity and reduced fibrosis. As such, these data suggest important counter-regulatory roles between MMP12 and ECM-degrading enzymes like MMP2, MMP9, and MMP13 in Th2 cytokine-driven fibrosis.
FoxP3+RORγt+ T Helper Intermediates Display Suppressive Function against Autoimmune Diabetes
Authors: Tartar Danielle M. , VanMorlan Amie M. , Wan Xiaoxiao , Guloglu F. Betul , Jain Renu , Haymaker Cara L. , Ellis Jason S. , Hoeman Christine M. , Cascio Jason A. , Dhakal Mermagya , Oukka Mohamed , Zaghouani Habib 
Published: February 2010

Abstract
Recently, traces of double-positive FoxP3+RORγt+ T cells were identified and viewed as dual programming differentiation intermediates geared toward development into T regulatory or Th17 cells. In this study, we report that FoxP3+RORγt+ intermediates arise in the NOD mouse T cell repertoire prior to inflammation and can be expanded with tolerogen without further differentiation. Furthermore, FoxP3+RORγt+ cells express both CD62L and membrane-bound TGFβ and use the former to traffic to the pancreas and the latter to suppress effector T cells both in vitro and in vivo. The cells perform these functions as FoxP3+RORγt+ intermediates, despite being able to terminally differentiate into either FoxP3+RORγt− T regulatory or FoxP3−RORγt+ Th17 cells on polarization. These previously unrecognized observations extend plasticity to both differentiation and function and indicate that the intermediates are poised to traffic to sites of inflammation and target diverse pathogenic T cells, likely without prior conditioning by effector T cells, thus broadening efficacy against autoimmunity.
The Septic Shock-Associated IL-10 −1082 A &gt; G Polymorphism Mediates Allele-Specific Transcription via Poly(ADP-Ribose) Polymerase 1 in Macrophages Engulfing Apoptotic Cells
Authors: Kang Xiaoyan , Kim Ha-Jeong , Ramirez Michelle , Salameh Sarah , Ma Xiaojing 
Published: February 2010

Abstract
The biallelic IL-10 single nucleotide polymorphism at −1082 of the promoter region linked to individual variation in cytokine inducibility has been strongly implicated in several pathological conditions including the development of, and outcomes in, septic shock during pneumococcal infection, acute respiratory distress syndrome, and cardiac dysfunction. However, the molecular basis of the single nucleotide polymorphism-mediated variable IL-10 production levels has not been explored. In this study, we report that the −1082G &gt; A alleles in the promoter region of the human IL-10 gene physically interact with a nuclear protein in an allele-specific manner that results in different levels of IL-10 transcription. This protein has been identified as poly(ADP-ribose) polymerase 1 (PARP-1). We show that PARP-1 acts as a transcription repressor, and its DNA-binding activity is strongly regulated in macrophages that engulf apoptotic cells but not stimulated with LPS. These findings unveil a novel role of PARP-1 in the regulation of IL-10 production in an allele-dependent way, which determines individual susceptibility to sepsis-induced inflammatory pathology and the immunological sequelae in a physiological process in which clearance of infection-induced apoptotic cells by professional phagocytes triggers the cytokine synthesis.
Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells
Authors: Thornton Angela M. , Korty Patricia E. , Tran Dat Q. , Wohlfert Elizabeth A. , Murray Patrick E. , Belkaid Yasmine , Shevach Ethan M. 
Published: February 2010

Abstract
Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4+CD8−Foxp3+ thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation (∼70%) of Foxp3+ T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-β expressed Helios. Ag-specific Foxp3+ T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3+ Treg cells are generated extrathymically.
Hydroxychloroquine treatment in a community‐based cohort of patients with systemic lupus erythematosus
Authors: Schmajuk Gabriela , Yazdany Jinoos , Trupin Laura , Yelin Edward 
Published: February 2010

AbstractObjectiveIn recent years hydroxychloroquine (HCQ) has emerged as a key therapy in systemic lupus erythematosus (SLE). We determined the rates of HCQ use in a diverse, community‐based cohort of patients with SLE and identified predictors of current HCQ use.MethodsPatients were participants in the University of California San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with confirmed SLE. We examined the prevalence of HCQ use per person‐year and compared baseline characteristics of users and nonusers, including demographic, socioeconomic, clinical, and health system use variables. Multiple logistic regression with generalized estimating equations was used to evaluate predictors of HCQ use.ResultsA total of 881 patients contributed 3,095 person‐years of data over 4 interview cycles. The prevalence of HCQ use was 55 per 100 person‐years and was constant throughout the observation period. In multivariate models, the odds of HCQ use were nearly doubled among patients receiving their SLE care from a rheumatologist compared with those identifying generalists or nephrologists as their primary sources of SLE care. In addition, patients with shorter disease duration were more likely to use HCQ, even after adjusting for age and other covariates.ConclusionIn this community‐based cohort of patients, HCQ use was suboptimal. Physician specialty and disease duration were the strongest predictors of HCQ use. Patients who are not using HCQ, those with longer disease duration, and those who see nonrheumatologists for their SLE care should be targeted for quality improvement.
Amyloid load in fat tissue reflects disease severity and predicts survival in amyloidosis
Authors: van Gameren Ingrid I. , Hazenberg Bouke P. C. , Bijzet Johan , Haagsma Elizabeth B. , Vellenga Edo , Posthumus Marcel D. , Jager Pieter L. , van Rijswijk Martin H. 
Published: February 2010

AbstractObjectiveThe severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival.MethodsWe studied all consecutive patients with systemic amyloidosis seen between January 1994 and January 2007 in our tertiary referral center. Congo red–stained abdominal fat smears were graded by 2 observers using a validated semiquantitative scoring system. Disease severity was measured by the total number of major organs involved and the extravascular retention of the serum amyloid P component (EVR24). The association of amyloid load in fat tissue with disease severity and overall survival was studied using multiple regression analysis.ResultsTwo hundred twenty patients were included in the study (120 with AL amyloidosis, 66 with AA amyloidosis, and 34 with ATTR amyloidosis). Amyloid grade in fat tissue was associated with the number of major organs involved and EVR24. Female sex turned out to be associated with a higher grade of amyloid in fat tissue than male sex. Amyloid grade in fat tissue was an independent predictor of decreased survival, as were heart involvement, the number of organs involved, AA or AL type of amyloid, and age.ConclusionThe amount of amyloid in subcutaneous fat tissue in systemic amyloidosis reflects disease severity, as measured by the number of organs involved and EVR24, and predicts decreased survival independent of other well‐known factors.
Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis
Authors: Radovits B. J. , Fransen J. , Al Shamma S. , Eijsbouts A. M. , van Riel P. L. C. M. , Laan R. F. J. M. 
Published: February 2010

AbstractObjectiveTo investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23‐year period in an inception cohort of rheumatoid arthritis (RA) patients.MethodsA prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time‐varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed.ResultsOf the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35–1.85) than in women (HR 1.21, 95% CI 1.04–1.42).ConclusionExcess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.