bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects
Authors: Hjelmervik Trond Ove R. , Petersen Kjell , Jonassen Inge , Jonsson Roland , Bolstad Anne Isine 
Published: May 2005

AbstractObjectiveTo identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjögren's syndrome (SS).MethodsA 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase–polymerase chain reaction techniques.ResultsWe found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up‐regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in ≥90% of primary SS patients and in ≤10% of the controls. Lymphotoxin β, as well as a number of major histocompatibility complex genes, cytokines, and lymphocyte activation factors, manifested its role in the pathogenesis of SS. Numerous type I interferon genes related to virus infection were found among the top 200 genes, with increased expression in primary SS. Interestingly, the expression of carbonic anhydrase II, which is essential in saliva production and secretion, and the apoptosis regulator Bcl‐2–like 2 were down‐regulated in primary SS patients.ConclusionWe have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up‐regulated or down‐regulated during disease, constituting an excellent platform for forthcoming functional studies.
The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort
Authors: Giesecke Thorsten , Gracely Richard H. , Williams David A. , Geisser Michael E. , Petzke Frank W. , Clauw Daniel J. 
Published: May 2005

AbstractObjectiveIndividuals with chronic pain frequently display comorbid depression, but the impact of symptoms of depression on pain processing is not completely understood. This study evaluated the effect of symptoms of depression and/or clinically diagnosed major depressive disorder (MDD) on pain processing in patients with fibromyalgia (FM).MethodsResults of quantitative sensory testing and neural responses to equally painful pressure stimuli (measured by functional magnetic resonance imaging [fMRI]) were compared with the levels of symptoms of depression and comorbid MDD among patients with FM.ResultsNeither the level of symptoms of depression nor the presence of comorbid MDD was associated with the results of sensory testing or the magnitude of neuronal activation in brain areas associated with the sensory dimension of pain (primary and secondary somatosensory cortices). However, symptoms of depression and the presence of MDD were associated with the magnitude of pain‐evoked neuronal activations in brain regions associated with affective pain processing (the amygdalae and contralateral anterior insula). Clinical pain intensity was associated with measures of both the sensory dimension of pain (results of sensory testing) and the affective dimension of pain (activations in the insula bilaterally, contralateral anterior cingulate cortex, and prefrontal cortex).ConclusionIn patients with FM, neither the extent of depression nor the presence of comorbid major depression modulates the sensory‐discriminative aspects of pain processing (i.e., localizing pain and reporting its level of intensity), as measured by sensory testing or fMRI. However, depression is associated with the magnitude of neuronal activation in brain regions that process the affective‐motivational dimension of pain. These data suggest that there are parallel, somewhat independent neural pain‐processing networks for sensory and affective pain elements. The implication for treatment is that addressing an individual's depression (e.g., by prescribing an antidepressant medication that has no analgesic properties) will not necessarily have an impact on the sensory dimension of pain.
Association of the risk of osteoarthritis with high innate production of interleukin‐1β and low innate production of interleukin‐10 ex vivo, upon lipopolysaccharide stimulation
Authors: Riyazi Naghmeh , Slagboom Eline , de Craen Anton J. M. , Meulenbelt Ingrid , Houwing‐Duistermaat Jeanine J. , Kroon Herman M. , van Schaardenburg Dirkjan , Rosendaal Frits R. , Breedveld Ferdinand C. , Huizinga Tom W. J. , Kloppenburg Margreet 
Published: May 2005

AbstractObjectiveIn a sibpair study of osteoarthritis (OA) patients, we investigated whether, upon stimulation with lipopolysaccharide (LPS), variations in the innate ex vivo production of interleukin‐1β (IL‐1β), IL‐1 receptor antagonist (IL‐1Ra), IL‐10, and tumor necrosis factor α (TNFα) in whole‐blood assays contribute to the risk of OA.MethodsData from 305 patients with OA at multiple sites (hand, knee, hip, and spine), whose median age was 60 years (range 43–79 years), were compared with those from 137 controls. OA was defined in accordance with the American College of Rheumatology criteria. Whole‐blood samples were stimulated with LPS (10 ng/ml). In the supernatants, cytokines were measured by enzyme‐linked immunosorbent assay. Odds ratios (ORs) were used as measures of the relative risk of OA in relation to quartiles of IL‐1β, IL‐1Ra, TNFα, and IL‐10 production. The ORs were adjusted for sex and age, and 95% confidence intervals (95% CIs) were computed using robust standard errors to take into account the intrafamily effect.ResultsSubjects in the highest quartile of IL‐1β and IL‐1Ra had an increased risk of OA (OR 3.3, 95% CI 1.4–7.9 and OR 8.0, 95% CI 3.7–17.4, respectively), while subjects in the lowest quartile of IL‐10 had a 3‐fold increased risk of OA (OR 3.1, 95% CI 1.5–6.5). High innate ex vivo production of TNFα was not associated with an increased risk of OA.ConclusionSubjects with a high innate ex vivo production of IL‐1β and IL‐1Ra and low innate ex vivo production of IL‐10 have an increased risk of OA. These results suggest that a proportion of the genetic susceptibility to OA may be encoded for by variations in innate cytokine activity.
Gene therapy targeting the Tie2 function ameliorates collagen‐induced arthritis and protects against bone destruction
Authors: Chen Ying , Donnelly Edwin , Kobayashi Hanako , DeBusk Laura M. , Lin P. Charles 
Published: May 2005

AbstractObjectiveIn a previous study, we demonstrated that Tie2 regulates angiogenesis in arthritis. The current study was performed to determine whether systemic delivery of a soluble Tie2 receptor (ExTek) using an adenoviral vector (AdExTek) as a Tie2 inhibitor affects arthritis development and progression in an animal model.MethodsWe used a collagen‐induced arthritis (CIA) mouse model to study the outcome of treatment with either AdExTek or a control vector. The onset, incidence, and severity of arthritis were quantified. Immunohistologic analysis of endothelium obtained from the paws was performed. Bone destruction in paws was analyzed using phase‐contrast radiography.ResultsThe data showed that systemic delivery of ExTek before disease development significantly inhibited the onset, incidence, and severity of arthritis. When AdExTek was given after disease onset, the severity of disease in mice treated with AdExTek was significantly lower than that in the control group at 35 days postimmunization, which correlated with significantly diminished angiogenesis in mouse paws. Strikingly, AdExTek treatment protected bone from erosion in the CIA model and reduced levels of RANKL. No differences in collagen‐specific antibodies were detected between these 2 groups.ConclusionWe demonstrated that blocking Tie2 receptor activation inhibits angiogenesis and arthritis development and protects against bone destruction in a CIA mouse model. These findings identify Tie2 as a therapeutic target for arthritis treatment and imply that interventions designed to target the Tie2 pathway could be clinically beneficial.
An international cohort study of cancer in systemic lupus erythematosus
Authors: Bernatsky S. , Boivin J. F. , Joseph L. , Rajan R. , Zoma A. , Manzi S. , Ginzler E. , Urowitz M. , Gladman D. , Fortin P. R. , Petri M. , Edworthy S. , Barr S. , Gordon C. , Bae S. C. , Sibley J. , Isenberg D. , Rahman A. , Aranow C. , Dooley M. A. , Steinsson K. , Nived O. , Sturfelt G. , Alarcón G. , Senécal J. L. , Zummer M. , Hanly J. , Ensworth S. , Pope J. , El‐Gabalawy H. , McCarthy T. , St. Pierre Y. , Ramsey‐Goldman R. , Clarke A. 
Published: May 2005

AbstractObjectiveThere is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population.MethodsWe assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person‐years in the cohort by the geographically matched age, sex, and calendar year–specific cancer rates, and summing over all person‐years.ResultsThe 9,547 patients from 23 centers were observed for a total of 76,948 patient‐years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05–1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13–3.49), and for non‐Hodgkin's lymphoma, it was 3.64 (95% CI 2.63–4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05–1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78).ConclusionThese results support the notion of an association between SLE and cancer and more precisely define the risk of non‐Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.
Development of proteoglycan‐induced arthritis is critically dependent on Fcγ receptor type III expression
Authors: Kaplan Charles D. , Cao Yancia , Verbeek J. Sjef , Tunyogi‐Csapo Miklos , Finnegan Alison 
Published: May 2005

AbstractObjectiveTo study the necessity for activating Fcγ receptor types I and III (FcγRI and FcγRIII) in proteoglycan‐induced arthritis (PGIA), a murine model of rheumatoid arthritis, and to determine whether usage of FcγRI or FcγRIII correlates with the Th1 phenotype or the autoantibody isotype in PGIA.MethodsPGIA was induced by immunizing FcγRI−/−, FcγRIII−/−, and wild‐type (WT) littermate mice with human PG. The development and severity of arthritis were monitored over time. PG‐specific T cell interleukin‐2 (IL‐2) production and B cell antibody responses were assessed. FcγRIII blocking antibodies were used to inhibit arthritis in an adoptive transfer system. Inflammation in the hind paws was evaluated by assessing cytokine and chemokine messenger RNA (mRNA) transcripts by real‐time polymerase chain reaction.ResultsFcγRI−/− mice developed arthritis with similar kinetics and severity as WT littermate controls, whereas FcγRIII−/− mice failed to develop the disease. Both FcγRI−/− and FcγRIII−/− mice produced similar amounts of PG‐specific antibody and IL‐2 as littermate controls. Transfer of arthritis was successfully blocked in mice treated with a blocking antibody against FcγRIII. FcγRIII−/− mice displayed a significant decrease in cytokine and chemokine mRNA transcripts obtained from the hind paws of immunized mice, whereas FcγRI−/− mice demonstrated a similar increase in cytokine and chemokine transcripts as controls.ConclusionThese results demonstrate that FcγRIII expression is critical to the development of PGIA, and usage of FcγRIII correlates with the IgG1 isotype of the PG‐specific antibody response. FcγRIII expression appears to be important in the effector phase of arthritis, possibly by activating cytokine‐ and chemokine‐secreting cells in the joint.
Ultraviolet radiation–induced injury, chemokines, and leukocyte recruitment: An amplification cycle triggering cutaneous lupus erythematosus
Authors: Meller Stephan , Winterberg Franziska , Gilliet Michel , Müller Anja , Lauceviciute Ingrida , Rieker Juliane , Neumann Norbert J. , Kubitza Robert , Gombert Michael , Bünemann Erich , Wiesner Ulrike , Franken‐Kunkel Petra , Kanzler Holger , Dieu‐Nosjean Marie‐Caroline , Amara Ali , Ruzicka Thomas , Lehmann Percy , Zlotnik Albert , Homey Bernhard 
Published: May 2005

AbstractObjectiveTo investigate the activation and recruitment pathways of relevant leukocyte subsets during the initiation and amplification of cutaneous lupus erythematosus (LE).MethodsQuantitative real‐time polymerase chain reaction was used to perform a comprehensive analysis of all known chemokines and their receptors in cutaneous LE lesions, and the cellular origin of these chemokines and receptors was determined using immunohistochemistry. Furthermore, cytokine‐ and ultraviolet (UV) light–mediated activation pathways of relevant chemokines were investigated in vitro and in vivo.ResultsIn the present study, we identified the CXCR3 ligands CXCL9 (interferon‐γ [IFNγ]–induced monokine), CXCL10 (IFNγ‐inducible protein 10), and CXCL11 (IFN‐inducible T cell α chemoattractant) as being the most abundantly expressed chemokine family members in cutaneous LE. Expression of these ligands corresponded with the presence of a marked inflammatory infiltrate consisting of mainly CXCR3‐expressing cells, including skin‐homing lymphocytes and blood dendritic cell antigen 2–positive plasmacytoid dendritic cells (PDCs). Within cutaneous LE lesions, PDCs accumulated within the dermis and were activated to produce type I IFN, as detected by the expression of the IFNα‐inducible genes IRF7 and MxA. IFNα, in turn, was a potent and rapid inducer of CXCR3 ligands in cellular constituents of the skin. Furthermore, we demonstrated that the inflammatory CXCR3 ligands cooperate with the homeostatic chemokine CXCL12 (stromal cell–derived factor 1) during the recruitment of pathogenically relevant leukocyte subsets. Moreover, we showed that UVB irradiation induces the release of CCL27 (cutaneous T cell–attracting chemokine) from epidermal compartments into dermal compartments and up‐regulates the expression of a distinct set of chemokines in keratinocytes.ConclusionTaken together, our data suggest an amplification cycle in which UV light–induced injury induces apoptosis, necrosis, and chemokine production. These mechanisms, in turn, mediate the recruitment and activation of autoimmune T cells and IFNα‐producing PDCs, which subsequently release more effector cytokines, thus amplifying chemokine production and leukocyte recruitment, finally leading to the development of a cutaneous LE phenotype.
Kappa and delta opioid receptors are expressed but down‐regulated in fibroblast‐like synoviocytes of patients with rheumatoid arthritis and osteoarthritis
Authors: Shen Hua , Aeschlimann André , Reisch Nataša , Gay Renate E. , Simmen Beat R. , Michel Beat A. , Gay Steffen , Sprott Haiko 
Published: May 2005

AbstractObjectiveTo investigate the expression and regulation of the κ‐opioid receptor (KOR) and the δ‐opioid receptor (DOR) in fibroblast‐like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to explore the potential antiarthritic mechanisms of peripheral KORs.MethodsFLS isolated from synovial tissues of 6 OA patients, 8 RA patients, and 2 healthy individuals were exposed to the selective KOR agonist U69593, the selective DOR agonist SNC 80, and κ‐opioid dynorphin A in the presence or absence of the KOR antagonist nor‐binaltorphimine, the DOR antagonist naltrindole, and the proinflammatory cytokines tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β). The expression of KOR and DOR in OA and RA FLS was evaluated on the messenger RNA (mRNA) and protein levels with TaqMan real‐time reverse transcriptase–polymerase chain reaction and immunofluorescence staining, respectively. KOR/DOR‐mediated activation of ERK‐1 and ERK‐2 was investigated by Western blotting.ResultsWe detected functional KOR and DOR in normal FLS and observed a reduction of both receptors in OA and RA FLS, which was more distinct in RA FLS. U69593 enhanced KOR mRNA expression in both OA and RA FLS in a KOR antagonist–reversible manner. However, the dose required for maximal enhancement in RA FLS was 10 times higher than that required in OA FLS. TNFα and IL‐1β both suppressed the expression of DOR and KOR mRNA in both OA and RA FLS.ConclusionDOR and KOR are constitutively present in normal FLS and are suppressed under inflammatory conditions, such as RA and OA. Most interestingly, the KOR agonist U69593 may exert an antiarthritic effect via up‐regulation of KOR in OA and RA FLS.
Why is it difficult to find comprehensive information? Implications of information scatter for search and design
Authors: Bhavnani Suresh K. 
Published: May 2005

AbstractThe rapid development of Web sites providing extensive coverage of a topic, coupled with the development of powerful search engines (designed to help users find such Web sites), suggests that users can easily find comprehensive information about a topic. In domains such as consumer healthcare, finding comprehensive information about a topic is critical as it can improve a patient's judgment in making healthcare decisions, and can encourage higher compliance with treatment. However, recent studies show that despite using powerful search engines, many healthcare information seekers have difficulty finding comprehensive information even for narrow healthcare topics because the relevant information is scattered across many Web sites. To date, no studies have analyzed how facts related to a search topic are distributed across relevant Web pages and Web sites. In this study, the distribution of facts related to five common healthcare topics across high‐quality sites is analyzed, and the reasons underlying those distributions are explored. The analysis revealed the existence of few pages that had many facts, many pages that had few facts, and no single page or site that provided all the facts. While such a distribution conforms to other information‐related phenomena, a deeper analysis revealed that the distributions were caused by a trade‐off between depth and breadth, leading to the existence of general, specialized, and sparse pages. Furthermore, the results helped to make explicit the knowledge needed by searchers to find comprehensive healthcare information, and suggested the motivation to explore distribution‐conscious approaches for the development of future search systems, search interfaces, Web page designs, and training.
A proposed mechanism for intermediate atresia ani (AA), based on a porcine case of AA and hypospadias
Authors: Finnigan Daniel F. , Fisher Ken R.S. , Vrablic Olga , Halina Winn G. , Partlow Gary D. 
Published: May 2005

AbstractBACKGROUNDAtresia Ani (AA) is one of the most common malformations of the lower gastrointestinal tract. It occurs in 1 in 1500 to 1 in 5000 human births. These patients suffer physically and psychologically from this disorder, and thus there is a research interest in the condition. There are 3 subcategories of AA: high, intermediate, and low. Each of these forms is likely related to separate etiological processes.METHODSAn anatomical study was performed on a porcine case of AA with a urorectal fistula and malformed urethra.RESULTSThis animal was found to have the intermediate form of AA.CONCLUSIONSA new mechanism is hypothesized, distinct from that described for the high and low forms of AA. This proposed mechanism involves the persistence of the cloacal membrane. Evidence to support this hypothesis includes: location of the urorectal fistula in the region of the embryonic cloacal duct, the lack of anomalies usually seen in conjunction with AA associated with mutations of the Sonic Hedgehog gene, and the presence of a malformed urethra, which is significantly correlated to intermediate AA. This form of AA could be related to a failure of the cloacal membrane to break down at the appropriate time during urorectal separation. Birth Defects Research (Part A), 2005. © 2005 Wiley‐Liss, Inc.
Effects of epidermal growth factor (EGF), transforming growth factor‐α (TGFα), and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on fusion of embryonic palates in serum‐free organ culture using wild‐type, EGF knockout, and TGFα knockout mouse strains
Authors: Abbott Barbara D. , Buckalew Angela R. , Leffler Korin E. 
Published: May 2005

AbstractBACKGROUND2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) is teratogenic in mice, producing cleft palate (CP). TCDD exposure disrupts expression of epidermal growth factor (EGF) receptor, EGF, and transforming growth factor‐α (TGFα) in the palate and affects proliferation and differentiation of medial epithelial cells. EGF knockout embryos are less susceptible to the induction of CP by TCDD. This study used palate organ culture to examine the hypothesis that EGF enables a response to TCDD.METHODSThe midfacial tissues from wild‐type (WT), EGF knockout, C57BL/6J, and TGFα knockout embryos were placed in organ culture on gestational day (GD) 12. Palatal explants were cultured for 4 days in serum‐free Bigger's (BGJ) medium with 0.1% dimethyl sulfoxide (DMSO) or 1 × 10−8 M TCDD with or without 2 ng of EGF/ml, 1 or 2 ng of TGFα/ml. Effects on palatal fusion were evaluated on day 4 of culture. EGF levels in explants and medium were determined using Luminex technology.RESULTSIn serum‐free, control medium, palates from all of the strains fused. EGF knockout palates cultured with TCDD (no EGF) fused, but those cultured with TCDD + 2 ng of EGF/ml failed to fuse (p < 0.05 vs. control or TCDD without EGF). TGFα knockout palates failed to fuse when cultured with TCDD + 2 ng of TGFα/ml. EGF levels increased in tissue and accumulated in the medium after 24 hr of culture.CONCLUSIONSThis study demonstrated that providing EGF to the palates of EGF knockout mice restored the response to TCDD. These studies support the hypothesis that the mechanism for induction of CP by TCDD is mediated via the EGFR pathway. Birth Defects Research (Part A), 2005. Published 2005 Wiley‐Liss, Inc.