bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence of serum apolipoprotein E4 isoprotein in rheumatoid arthritis patients with amyloidosis
Authors: Hasegawa Hisashi , Nishi Shin‐Ichi , Ito Satoshi , Saeki Takako , Kuroda Takeshi , Kimura Hideki , Watababe Takeshi , Nakano Masaaki , Gejyo Fumitake , Arakawa Masaaki 
Published: February 2007

AbstractObjective. To determine whether serum Apolipoprotein E (Apo E) type 4 isoprotein is a risk factor for the development of amyloidosis in patients with rheumatoid arthritis (RA).Methods. Using isoelectric focusing, we studied Apo E phenotype expression and the corresponding allele frequencies (ϵ2, ϵ3, and ϵ4) in 35 patients with RA and amyloidosis, 65 patients with RA and without amyloidosis, and 63 healthy controls.Results. The Apo E3/4 phenotype was significantly more common in the group with amyloidosis (31.4%) than in the patients without amyloidosis (12.3%; P < 0.05) or in healthy controls (12.7%; P < 0.05). The frequency of the ϵ4 allele was significantly greater in the group with amyloidosis (0.16) than in the patients without amyloidosis (0.07; P < 0.05) or in healthy controls (0.07; P < 0.05).Conclusion. The presence of Apo E4 isoprotein may be a risk factor for the development of amyloidosis in patients with RA.
Autoreactivity to human heat‐shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis
Authors: Prakken A. B. J. , van Eden W. , Rijkers G. T. , Kuis W. , Toebes E. A. , de Graeff‐Meeder E. R. , van der Zee R. , Zegers B. J. M. 
Published: February 2007

AbstractObjective. To determine whether T lymphocyte reactivity to endogenous human hsp60 plays a regulatory role in the course of oligoarticular juvenile rheumatoid arthritis (JRA).Methods. A prospective, longitudinal study of T cell reactivity to HSP in 15 patients with newly diagnosed HLA‐B27 negative oligoarticular JRA was performed. Results were compared with those in a group of 20 patients with newly diagnosed polyarticular or systemic JRA or with acute arthritis caused by other systemic diseases or viral infections, as well as with those in a group of 9 healthy control subjects.Results. In 86% of the patients with oligoarticular JRA (13 of 15), significant T lymphocyte proliferative responses to hsp60 were found in peripheral blood mononuclear cells and/or synovial fluid mononuclear cells within 3 months after the onset of arthritis. Only 5% of the patients in the rheumatologic disease control group (1 of 20) showed such positivity. All patients with oligoarticular JRA and positive responses to human hsp60 developed a remission of their disease within 12 weeks. During this period of remission, blood samples were taken from 8 patients and showed significantly lower and even negative responses to hsp60, compared with active disease, when all 8 patients had good responses.Conclusion. The results show that significant proliferative responses to human hsp60 can be found early in the course of oligoarticular JRA. Furthermore, these responses correlate with disease activity in such a manner that T cell reactivity to human hsp60 seems to be associated with disease remission.
Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy
Authors: Arenas Joaquin , Gonzalez‐Crespo Maria R. , Campos Yolanda , Martin Miguel A. , Cabello Ana , Gomez‐Reino Juan J. 
Published: February 2007

AbstractObjective. To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies.Methods. Six men and 7 women with inflammatory myopathy and 25 age‐matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed.Results. Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes.Conclusion. Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.
Lymphocyte apoptosis and apoptosis‐associated gene expression in Sjögren's syndrome
Authors: Ogawa Noriyoshi , Dang Howard , Kong Liping , Anaya Juan‐Manuel , Liu George Tye , Talal Norman 
Published: February 2007

AbstractObjective. To study the mechanism and regulation of apoptosis in peripheral blood T and B lymphocytes from patients with Sjögren's syndrome (SS).Methods. The mode of in vitro lymphocyte death in the peripheral blood of patients with SS was determined by fluorescence microscopic analysis, terminal deoxynucleotidyl transferase assay, and DNA fragmentation analysis. Apoptotic cell death of T and B cells was determined at 48 hours of culture by fluorescence‐activated cell sorter analysis of propidium iodidestained cells. Messenger RNA (mRNA) expression of bcl‐2, bcl‐x, bax, and c‐myc in T and B cells was determined by enzyme‐linked immunosorbent assaypolymerase chain reaction (ELISA‐PCR). Expression of bcl‐xL and bcl‐xS was determined by Southern blot analysis of PCR products. Gene expression was calculated as the ratio of each gene message to the message of the GAPDH gene. Bcl‐2 protein levels in SS T cells were determined by ELISA.Results. SS T cells showed increased in vitro apoptosis compared with normal T cells (mean ± SD 12.3 ± 4.5% versus 7.3 ± 2.0%; P < 0.01). Freshly isolated SS T cells showed increased expression of bcl‐2 mRNA compared with normal controls (mean ± SD 1.50 ± 0.65 versus 0.88 ± 0.23; P < 0.05). There was no significant difference in levels of bax or c‐myc mRNA in T cells and B cells between SS patients and normal controls. When SS T lymphocytes were cultured in vitro for 72 hours, Bcl‐2 protein levels decreased with time.Conclusion. SS T cells showed accelerated apoptosis in vitro. Freshly isolated SS T cells had increased expression of bcl‐2. An increase in death‐promoter signals and decrease in death‐suppressor signals in vitro may have been responsible, in part, for the apoptosis in SS T lymphocytes.
Specificities of human tap alleles for HLA—B27 binding peptides
Authors: Kuipers Jens G. , Raybourne Richard B. , Williams Kristina M. , Zeidler Henning , Yu David Tak Yan 
Published: February 2007

AbstractObjective. Allelic TAP polymorphism has been linked to susceptibility to Reiter's syndrome and was suggested to influence disease phenotype in HLA‐B27 positive patients with ankylosing spondylitis. In the present study, we examined whether the human TAP alleles functionally differ in their translocation specificity for HLA‐B27‐binding nonamers.Methods. TAP translocation of a panel of HLA‐B27‐binding peptides was measured with a labeled reporter peptide containing an N‐linked glycosylation acceptor site in streptolysin O‐permeabilized cells with different TAP alleles.Results. The different human TAP alleles tested did not measurably differ in their peptide specificity.Conclusion. The polymorphism of human TAP does not affect the translocated repertoire of HLA‐B27 ligands and is therefore unlikely to play a decisive role in the development of HLA‐B27‐associated disease.
Synovial distribution of αd/CD18, a novel leukointegrin. Comparison with other integrins and their ligands
Authors: El‐Gabalawy Hani , Canvin Janice , Ma Guoping M. , van der Vieren Monica , Hoffman Patricia , Gallatin Michael , Wilkins John 
Published: February 2007

AbstractObjective. To define the synovial distribution of the novel leukointegrin αd/CD18, and compare this with other members of the β2‐integrin family of adhesion molecules, and their counter‐receptors.Methods. Monoclonal antibodies to the CD3, CD14, CD29, CD68, β2‐integrin, and immunoglobulin supergene families were used to immunohistologically define the distribution of these molecules in synovial tissue samples from normal subjects and osteoarthritis (OA) and rheumatoid arthritis (RA) patients.Results. The normal synovial lining cell layer (SLC) expresses CD68, vascular cell adhesion molecule 1, β1‐integrin (CD29), the β2‐integrins CD11b/CD18 (αm/β2, Mac‐1), and α/CD18, whereas CD11a/CD18 (αL/β2, lymphocyte function‐associated antigen 1) and CD11c/CD18 (αx/β2, gp150/95) expression is generally absent. In RA synovitis, expression of β2‐integrins in the SLC increases in proportion to the degree of hyperplasia. The ratio of cells in the SLC which express CD11c/CD18 increases substantially, approaching that of CD11b/CD18 and αd/CD18, while there is minimal increase in CD11a/CD18 expression. In the sublining areas of the tissues, aggregates and diffuse infiltrates of CD3/CD11a/ICAM‐3+ lymphocytes are interspersed among CD68/CD14/CD11b/αd+ macrophages. A number of aggregates demonstrate intense αd staining of the lymphocytes. The synovial endothelium variably expresses intercellular adhesion molecule‐1 (ICAM‐1), ICAM‐2, and vascular cell adhesion molecule 1 (VCAM‐1), with minimal evidence of ICAM‐3 expression.Conclusion. The leukointegrin αd/CD18 is expressed constitutively by synovial macrophages and macrophage‐like lining cells. In rheumatoid synovitis, the intense coexpression of this integrin and its known counter‐receptor, ICAM‐3, in the inflammatory infiltrates, suggests a potential role for this adhesion pathway in cellular interactions occurring the synovium.
Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation
Authors: Mahmud Taher , Rafi Sue S. , Scott David L. , Wrigglesworth John M. , Bjarnason Ingvar 
Published: February 2007

AbstractObjective. There is a lack of correlation between cyclooxygenase (COX) inhibition and nonsteroidal antiinflammatory drug (NSAID)—induced gastrointestinal (GI) damage; it has been suggested that mucosal damage may be initiated by a “topical” action of NSAIDs involving mitochondrial injury. We evaluated the effect of a range of NSAIDs and related compounds on mitochondrial function and assessed the differences between them in relation to their physicochemical properties.Methods. Stimulation of respiration, as an indicator of mitochondrial uncoupling, was measured in isolated coupled rat liver mitochondrial preparations, using an oxygen electrode.Results. Conventional NSAIDs and acidic prodrugs all had stimulatory effects on mitochondrial respiration at micromolar concentrations (0.02–2.7 μM); higher concentrations were inhibitory. The uncoupling potency was inversely correlated with drug pKa (r = −0.87, P < 0.001; n = 12). Drugs known to have good GI tolerability, including modified flurbiprofen (dimeroflurbiprofen and nitrobutyl‐flurbiprofen), nabumetone (a non‐acidic prodrug), and non‐acidic highly selective COX‐2 inhibitors, did not cause uncoupling.Conclusion. The ability to uncouple mitochondrial oxidative phosphorylation is a common characteristic of antiinflammatory agents with an ionizable group. Modification or absence of an ionizable moiety reduces the effect on mitochondria and could lead to improved NSAID GI safety.
Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease
Authors: Kozora Elizabeth , Thompson Laetitia L. , West Sterling G. , Kotzin Brian L. 
Published: February 2007

AbstractObjective. To examine cognitive and psychological functioning in relation to antiribosomal P protein autoantibodies in patients with systemic lupus erythematosus (SLE) who had no previous history of central nervous system disease (non‐CNS SLE).Methods. Comprehensive neuropsychological and psychological tests were administered to 51 non‐CNS SLE patients, 29 rheumatoid arthritis (RA) patients, and 27 healthy controls.Results. Twenty‐nine percent of the non‐CNS SLE patients, 31% of the RA patients, and 11% of the control subjects were classified as cognitively impaired. Similar reductions in intelligence, attention, and fluency were detected in the non‐CNS SLE and RA patients compared with controls. The non‐CNS SLE patients showed a distinct deficit in learning compared with the RA and control groups. Forty‐two percent of the non‐CNS SLE patients demonstrated psychological distress, compared with 7% of the RA patients and 6% of the controls. In the patient groups, neither cognitive dysfunction nor psychological distress was associated with disease activity or prednisone dosage. Elevated serum levels of autoantibodies to ribosomal P protein were not associated with either psychological or cognitive abnormalities.Conclusion. These results suggest that certain cognitive deficits in non‐CNS SLE patients may not be specific to the immunopathology of SLE. In contrast, it is possible that deficits in learning, as well as psychological distress without major psychiatric pathology, may be subtle manifestations of CNS lupus.
T cell cytokine pattern in the joints of patients with lyme arthritis and its regulation by cytokines and anticytokines
Authors: Yin Zhinan , Braun Jürgen , Neure Lucia , Wu Peihua , Eggens Ulrich , Krause Andreas , Kamradt Thomas , Sieper Joachim 
Published: February 2007

AbstractObjective. To investigate whether type 1 helper (Th1) or Th2 cytokines are found in the joints of patients with Lyme arthritis, and whether the cytokine pattern can be modulated by cytokines or anticytokines.Methods. The cytokine pattern in the joints of 10 patients with Lyme arthritis was investigated. Expression of interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐4 (IL‐4), and IL‐10 was measured by enzyme‐linked immunosorbent assay (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with Borrelia burgdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied using semiquantitative reverse transcriptase‐polymerase chain reaction and immunohistologic techniques. The effects of recombinant cytokines or neutralizing anticytokine antibodies on cytokine production in Bb‐stimulated SFMC were investigated by ELISA.Results. SFMC produced high amounts of IFNγ and TNFα, but little or no IL‐4, upon stimulation with Bb antigen, indicating a Th1‐type cytokine pattern. In SM, IFNγ was detectable in all patients, while the other cytokines were less frequently found. Serial sections of SM revealed that all cytokines were located in the same area. The Th1 response, especially the production of TNFα, could be down‐regulated in vitro by both endogenous and exogenous IL‐10, but not by IL‐4 or anti‐IL‐12.Conclusion. A Th1‐type cytokine pattern was found in the joints of patients with Lyme arthritis. This Th1 response could be down‐regulated by IL‐10, suggesting insufficient IL‐10 production in vivo.
Prevention of cytokine‐induced changes in leukocyte adhesion receptors by nonsteroidal antiinflammatory drugs from the oxicam family
Authors: García‐Vicuña Rosario , Díaz‐González Federico , González‐Alvaro Isidoro , Del Pozo Miguel A. , Mollinedo Faustino , Cabañas Carlos , González‐Amaro Roberto , Sánchez‐Madrid Francisco 
Published: February 2007

AbstractObjective. To explore the effect of the nonsteroidal antiinflammatory drugs (NSAIDs) piroxicam and meloxicam on quantitative and qualitative changes in leukocyte adhesion receptors induced by cytokines and other activation stimuli.Methods. The expression of CD11b and L‐selectin during neutrophil activation with tumor necrosis factor α (TNFα), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), FMLP, phorbol myristate acetate (PMA), and calcium ionophore A23187 was assessed by flow cytometry. Enzyme‐linked immunosorbent assays were used to quantitate soluble L‐selectin shed after neutrophil stimulation. Enzyme release was measured to determine neutrophil degranulation by proinflammatory stimuli. Changes in affinity state of β1 and β2 integrins after neutrophil and T lymphocyte stimulation were assessed, by flow cytometry, using the monoclonal antibodies (MAb) HUTS‐21 (anti‐β1) and CBRM1/5 (anti‐CD11b), which recognize activation‐dependent epitopes on these two integrins.Results. Pretreatment of neutrophils with either NSAID prevented the changes in L‐selectin and CD11b expression induced by TNFα, GM‐CSF, and FMLP, but not those induced by PMA or A23187. Furthermore, piroxicam significantly decreased the amount of L‐selectin shed by cytokine‐treated neutrophils, whereas it did not exert this effect on PMA‐ or A23187‐treated neutrophils. Piroxicam also decreased the release of gelatinase and lysozyme induced by TNFα, but not by PMA. Interestingly, piroxicam prevented the conformational changes that β2 integrins underwent upon activation of neutrophils: the appearance of the activation epitope of CD11b, detected by the CBRM1/5 MAb, was blocked by piroxicam in TNFα‐treated neutrophils. Moreover, in chemokine‐treated T lymphocytes, the expression of activation epitopes on β1 integrins was also diminished by piroxicam. In contrast, this NSAID did not affect the β1 integrin conformational changes induced by PMA or Mn++.Conclusion. Our results indicate that members of the oxicam family are able to interfere with events of neutrophil function, such as their degranulation and cytokine‐mediated activation changes in adhesion molecules, both in neutrophils and in lymphocytes. Such effects may significantly contribute to the antiinflammatory activity of these drugs.
Quantitative studies of the risk of serious hepatic injury in persons using nonsteroidal antiinflammatory drugs
Authors: Walker Alexander M. 
Published: February 2007

AbstractObjective. To quantify the risk of symptomatic hepatic injury associated with nonsteroidal antiinflam‐matory drugs (NSAIDs).Methods. Five population‐based studies were summarized to evaluate information on more than 1,000,000 patients using NSAIDs.Results. The risk of clinically apparent liver injury was ˜ 1 case per 10,000 patient‐years of NSAID use. Only sulindac, associated with a 5–10‐fold higher incidence of hepatic injury, differed significantly from other NSAIDs. Patients using diclofenac showed no higher incidence of serious liver disease than did patients using other NSAIDs.Conclusion. Symptomatic hepatic effects attributable to most NSAIDs are extremely rare and usually mild.
Involvement of nuclear factor kB in the regulation of cyclooxygenase‐2 expression by interleukin‐1 in rheumatoid synoviocytes
Authors: Crofford Leslie J. , Tan Bing , McCarthy Conor J. , Hla Timothy 
Published: February 2007

AbstractObjective. To evaluate involvement of the transcription factor nuclear factor kB (NF‐kB) in the increased expression of cyclooxygenase‐2 (COX‐2) stimulated by interleukin‐1β (IL‐1β) in primary rheumatoid synoviocytes.Methods. We treated early‐passage rheumatoid synoviocytes with IL‐1β and examined the time course of NF‐kB translocation to the nucleus by Western blot analysis, as well as NF‐kB binding to the COX‐2 promoter/enhancer by electrophoretic mobility shift assay. We correlated the time course of NF‐kB binding with expression of COX‐2 messenger RNA (mRNA) and protein. Synoviocytes were then treated with either sense or antisense phosphorothioate‐modified oligonucleotides derived from the transcription start site of the human NF‐kB p65 RNA. We analyzed NF‐kB binding to the COX‐2 promoter and COX‐2 protein levels after these treatments.Results. IL‐1β rapidly stimulated the translocation of the p65, p50, and c‐rel NF‐kB subunits from the cytoplasm to the nucleus. Electrophoretic mobility shift assay demonstrated binding to 2 NF‐kB sites within the COX‐2 promoter/enhancer, with a time course identical to that of nuclear localization of NF‐kB. Supershift analysis revealed that binding activity was due primarily to the p65–p50 heterodimer and the p50 homodimer. With appropriate lag time after NF‐kB binding, COX‐2 mRNA and protein were increased. Pretreatment of RA synoviocytes with NF‐kB p65 antisense oligonucleotides resulted in decreased binding to the COX‐2 promoter and decreased COX‐2 protein expression.Conclusion. These data demonstrate that signaling via the NF‐kB pathway is involved in regulation of COX‐2 expression induced by IL‐1β in RA synoviocytes.
HLA markers and prediction of clinical course and outcome in rheumatoid arthritis
Authors: Wagner Ulf , Kaltenhäuser Sylke , Sauer Heidemarie , Arnold Sybille , Seidel Wolfram , Häntzschel Holm , Kalden Joachim R. , Wassmuth Ralf 
Published: February 2007

AbstractObjective. To evaluate HLA markers as early prognostic factors for disease severity in rheumatoid arthritis (RA).Methods. HLA genotyping was carried out in a retrospective analysis of 66 RA patients and in a prospective study of 55 RA patients and 87 healthy controls using polymerase chain reaction‐based methods for HLA‐DRB1 specificities, DR4 alleles, and their linked DQB1 alleles, as well as HLA‐B27. The clinical course of RA was assessed by clinical and radiologic scores. The impact of HLA markers was evaluated by epidemiologic means in addition to modeling using multiple logistic regression analysis.Results. Shared epitope‐positive (HVR3+) DR4 alleles and the HVR3 amino acid cassette QKRAA were associated with RA in both longstanding (relative risk [RR] 3.34 and 3.19) and recent‐onset (RR 2.1 and 2.37) RA. In longstanding RA, radiologic evidence of severe joint destruction (Larsen score > 1.62) was seen more often in HVR3 shared epitope‐positive patients than in epitope‐negative patients (odds ratio [OR] = 25.67, X2 = 13.59, P = 0.0003). Moreover, rank sum analysis of Larsen indices indicated significantly higher ranking for the presence of the RA‐associated HVR3 cassettes (QKRAA, QRRAA) when expressed on a DR4 allele (P < 0.0001). In the prospective study, DR4‐positive patients had a significantly increased risk (OR = 13.75, P = 0.00083) of developing bony erosions. In addition, HVR3 epitope‐positive DR4‐positive individuals had significantly higher Larsen indices than did epitope‐negative patients (P = 0.0083). In particular, the presence of the HVR3 epitope on DR4 resulted in an increased a posteriori likelihood (0.91) of developing early erosive disease compared with an a priori risk of 0.62. Conversely, the likelihood decreased to a minimum of 0.35 when the HVR3 epitope was absent.Conclusion. While the contribution of HLA typing to establishing the diagnosis of RA is limited, HLA‐DR genotyping and DR4 subtype determination provide valuable markers for the prognosis of joint destruction in RA.
Perceived physical and emotional trauma as precipitating events in fibromyalgia. Associations with health care seeking and disability status but not pain severity
Authors: Aaron Leslie A. , Bradley Laurence A. , Alarcón Graciela S. , Triana‐Alexander Mireya , Alexander Ronald W. , Martin Michelle Y. , Alberts Kristin R. 
Published: February 2007

AbstractObjective. We examined relationships between perceived physical and emotional trauma that occur prior to, or that initiate, pain onset and health care seeking for fibromyalgia syndrome (FMS). We also assessed associations between perceived trauma and levels of health care usage, symptom severity, functional disability, and receipt of disability compensation among patients with FMS.Methods. We evaluated these variables using interviews and standardized instruments in a consecutive series of FMS patients and community residents who met the American College of Rheumatology criteria for FMS but had not sought medical care (“nonpatients”).Results. Emotional trauma was associated with status as an FMS patient independently of demographics, physical trauma, and sexual/physical abuse (P = 0.007). Among patients, emotional trauma was related to a high number of physician visits (P = 0.013), functional disability ratings (P = 0.012), and fatigue (P = 0.029), but physical trauma was associated with receipt of disability compensation (P = 0.019). Trauma history was not related to pain severity or pain thresholds.Conclusion. Perception of physical trauma is a greater determinant of disability compensation for FMS than is perceived emotional trauma, symptom severity, or functional disability. Effort should be devoted to understanding the social and legal factors underlying this observation, as well as to reducing high health care usage among FMS patients with emotional trauma.